Date:
November 21, 2017

Source:
European Geosciences Union

Summary:
From Trump to Heinz, some of America’s most famous family names and brands trace their origins back to Germans who emigrated to the country in the 19th century. Researchers have now found that climate was a major factor in driving migration from Southwest Germany to North America during the 19th century.

 

Ellis Island National Museum of Immigration, Upper New York Bay.
Credit: © littleny / Fotolia

 

 

In the 19th century, over 5 million Germans moved to North America. It was not only a century of poverty, war and revolutions in what is now Germany, but also of variable climate. Starting at the tail end of the cold period known as the Little Ice Age, the century saw glacier advances in the Alps, and a number of chilly winters and cool summers, as well as other extreme weather events such as droughts and floods.

“Overall, we found that climate indirectly explains up to 20-30% of migration from Southwest Germany to North America in the 19th century,” says Rüdiger Glaser, a professor at the University of Freiburg, Germany, and lead-author of the Climate of the Paststudy.

The researchers could see a climate signature in most major migration waves from Southwest Germany during the 19th century. “The chain of effects is clearly visible: poor climate conditions lead to low crop yields, rising cereal prices and finally emigration,” says Glaser. “But it is only one piece of the puzzle.”

“Our results show that the influence of climate was marked differently during the different migration waves,” adds Iso Himmelsbach, another of the researchers at the University of Freiburg who took part in the study.

The team studied official migration statistics and population data from the 19th century, as well as weather data, harvest figures and cereal-price records. They focused on the region that is now the Baden-Württemberg state, where many of the migrants — such as Charles Pfizer of pharmaceutical fame — originated from. They started by identifying the major migration waves and then investigated to what extent climate played a role in driving people to North America during each of them.

The first wave followed the eruption of the Tambora volcano in Indonesia in 1815. The volcanic ash and gases spewed into the atmosphere caused temperatures to drop around the world for a few years after the eruption. The ‘year without summer’, 1816, was wet and cold causing widespread crop failures, famine and emigration.

“Another peak-migration year, 1846, had an extremely hot and dry summer leading to bad harvests and high food prices,” says Annette Bösmeier, a researcher at the University of Freiburg who also involved in the study. “These two years of high migration numbers appear to be quite strongly influenced by climate changes, while for other migration waves other circumstances appeared to be more important,” she adds.

Climate was a less significant factor in driving the largest emigration wave, from 1850 to 1855, the researchers found. While unfavourable weather affected crops resulting in low harvests during this time, other factors also drove up food prices. During the Crimean War (1853-1856), for example, France banned food exports, putting pressure on the German grain markets. At the time, the authorities of Baden also paid the poorest people to leave the country in an attempt to prevent uprisings and save on welfare. This, too, drove up emigration numbers.

“Migration in the 19th century was a complex process influenced by multiple factors. Lack of economic perspectives, social pressure, population development, religious and political disputes, warfare, family ties and the promotion of emigration from different sides influenced people’s decision to leave their home country,” concludes Glaser. “Nevertheless, we see clearly that climate was a major factor.”

In the past few years, climate has taken a central stage in migration discussions since future climate change is expected to lead to mass migration (‘climate refugees’), as sea levels rise and extreme weather events, such as floods, droughts and hurricanes, become more frequent. The team hope their study can shed some light on the various factors influencing migration and how important climate can be in triggering mass movements of people.

Story Source:

Materials provided by European Geosciences UnionNote: Content may be edited for style and length.


Journal Reference:

  1. Rüdiger Glaser, Iso Himmelsbach, Annette Bösmeier. Climate of migration? How climate triggered migration from southwest Germany to North America during the 19th centuryClimate of the Past, 2017; 13 (11): 1573 DOI: 10.5194/cp-13-1573-2017

 

Source: European Geosciences Union. “Climate changes triggered immigration to America in the 19th century, study finds.” ScienceDaily. ScienceDaily, 21 November 2017. <www.sciencedaily.com/releases/2017/11/171121095201.htm>.

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Planet appears to have water-restricted environment

Date:
November 20, 2017

Source:
US Geological Survey

Summary:
Dark features previously proposed as evidence for significant liquid water flowing on Mars have now been identified as granular flows, where sand and dust move rather than liquid water, according to a new article. These findings indicate that present-day Mars may not have a significant volume of liquid water. The water-restricted conditions that exist on Mars would make it difficult for Earth-like life to exist near the surface.

 

This HiRISE image cutout shows Recurring Slope Lineae in Tivat crater on Mars in enhanced color. The narrow, dark flows descend downhill (towards the upper left). Analysis shows that the flows all end at approximately the same slope, which is similar to the angle of repose for sand.
Credit: NASA/JPL/University of Arizona/USGS

 

 

Dark features previously proposed as evidence for significant liquid water flowing on Mars have now been identified as granular flows, where sand and dust move rather than liquid water, according to a new article published in Nature Geoscience by the U.S. Geological Survey.

These new findings indicate that present-day Mars may not have a significant volume of liquid water. The water-restricted conditions that exist on Mars would make it difficult for Earth-like life to exist near the surface of the planet.

Scientists from the USGS, the University of Arizona, Durham University (England) and the Planetary Science Institute analyzed narrow, down-slope trending surface features on Mars that are darker than their surroundings, called Recurring Slope Lineae, or RSL. These RSL features grow incrementally, fade when inactive and recur annually during the warmest time of year on Mars. RSL are mostly found on steep rocky slopes in dark regions of Mars, such as the southern mid-latitudes, Valles Marineris near the equator, and in Acidalia Planitia on the northern plains. The appearance and growth of these features resemble seeping liquid water, but how they form remains unclear, and this research demonstrated that the RSL flows seen by HiRISE are likely moving granular material like sand and dust.

“We’ve thought of RSL as possible liquid water flows, but the slopes are more like what we expect for dry sand,” said USGS scientist and lead author Colin Dundas. “This new understanding of RSL supports other evidence that shows that Mars today is very dry.”

The terminal end of the RSL slopes, said Dundas, are identical to the slopes of sand dunes where movement is caused by dry granular flows. Water almost certainly is not responsible for this behavior, which would require the volume of liquid to correspond to the length of slope available, producing more liquid on longer slopes. Instead, the 151 RSL examined by the study authors all end on similar slopes despite very different lengths. Additionally, said the scientists, water is unlikely to be produced only near the tops of slopes at these angles and if it were, it should be able to flow onto lower slopes.

This new research finds that these RSL features are flows of granular material and thus, align with the long-standing hypothesis that the surface of Mars lacks flowing water. Small amounts of water could still be involved in their initiation in some fashion, as hydrated minerals have been detected at some RSL locations. The authors conclude that liquid on present-day Mars may be limited to traces of dissolved moisture from the atmosphere and thin films of water.

Story Source:

Materials provided by US Geological SurveyNote: Content may be edited for style and length.


Journal Reference:

  1. Colin M. Dundas, Alfred S. McEwen, Matthew Chojnacki, Moses P. Milazzo, Shane Byrne, Jim N. McElwaine, Anna Urso. Granular flows at recurring slope lineae on Mars indicate a limited role for liquid waterNature Geoscience, 2017; DOI: 10.1038/s41561-017-0012-5

 

Source: US Geological Survey. “Previous evidence of water on Mars now identified as grainflows: Planet appears to have water-restricted environment.” ScienceDaily. ScienceDaily, 20 November 2017. <www.sciencedaily.com/releases/2017/11/171120124457.htm>.

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Sunset in New York City

 

As the holiday season approaches, and the days are shorter, the sunsets in NYC are breath-taking. Fortunately, the corner offices on the 24th floor faces SW, so the views are beyond spectacular.

Words cannot describe this gorgeous view from the 24th Floor.  ©Target Health Inc.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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FDA Approves Pill With Sensor That Digitally Tracks if Patients Have Ingested Their Medication

FDA.gov

 

 

Last week, the U.S. Food and Drug Administration approved the first drug in the U.S. with a digital ingestion tracking system. Abilify MyCite, are aripiprazole tablets with sensor. Abilify has an ingestible 1) ___ embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and for use as an add-on treatment for depression in adults. The system works by sending a message from the pill’s sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smart 2) ___. Patients can also permit their caregivers and physician to access the information through a web-based portal.

 

“Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,“ said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “The FDA supports the development and use of new technology in prescription 3) ___ and is committed to working with companies to understand how technology might benefit patients and prescribers.“

 

It is important to note that Abilify MyCite’s prescribing information (labeling or package 4) ___) notes that the ability of the product to improve patient compliance with their treatment regimen has not been shown. Abilify MyCite should not be used to track drug ingestion in “real-time“ or during an emergency because detection may be delayed or may not occur.

 

Schizophrenia is a chronic, severe and disabling brain disorder. About 1% of Americans have this illness. Typically, symptoms are first seen in adults younger than 30 years of age. Symptoms of those with schizophrenia include hearing 5) ___, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn. Bipolar disorder, also known as 6) ___-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high or irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.

 

Abilify MyCite contains a Boxed Warning alerting health care professionals that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of 7) ___. Abilify MyCite is not approved to treat patients with dementia-related psychosis. The Boxed Warning also warns about an increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. The safety and effectiveness of Abilify MyCite has not been established in pediatric patients. Patients should be monitored for worsening and emergence of suicidal thoughts and behaviors. Abilify MyCite must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and 8) ___.

 

In the clinical trials for Abilify, the most common side effects reported by adults taking Abilify were nausea, vomiting, constipation, headache, dizziness, uncontrollable limb and body movements (akathisia), anxiety, insomnia, and restlessness. Skin irritation at the site of the MyCite patch placement may occur in some patients. Prior to initial patient use of the product, the patient’s health care professional should facilitate use of the drug, patch and app to ensure the patient is capable and willing to use the system.

 

Abilify was first approved by the FDA or 9) ___ and ___ ___, in 2002 to treat schizophrenia. The ingestible sensor used in Abilify MyCite was first permitted for marketing by the FDA in 2012. The FDA granted the approval of Abilify MyCite to Otsuka Pharmaceutical Co., Ltd. The sensor technology and patch are made by Proteus Digital Health.

 

The FDA, an agency within the U.S. Department of Health and 10) ___ Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

 

ANSWERS: 1) sensor; 2) phone; 3) drugs; 4) insert; 5) voices; 6) manic; 7) death; 8) risks; 9) Food and Drug Administration; 10) Human

 

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A Short History of Pills

An old Cadmach rotary tablet press

Photo credit: Slashme at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=21895660

 

 

Pills date back to roughly 1500 BCE. They were presumably invented so that measured amounts of a medicinal substance could be delivered to a patient. A long time ago, around 4,000 years or so, medicines were generally liquid preparations. An inscription on an Assyrian clay tablet instructs the user to pulverize various seeds, plant resins and leaves together–then dissolve them in beer. Pills are first referenced in ancient Egyptian. One famous set of papyruses is filled with medical remedies, including pills made from bread dough, honey or grease. Medicinal plants would be reduced to powders, and other active ingredients, and would then be mixed with these substances–then little balls, or pills, would be formed with the fingers. Early ingredients of pills included saffron, myrrh, cinnamon, tree resins and many other botanicals. Pills came in various sizes as well as flat and round, and other assorted shapes. As far back as 500 BCE, some were even trademarked with special indentations in the pills.

 

Hippocrates, knew about the curative powers of willow bark. And in ancient Greece, the round balls or other shapes were called katapotia (meaning “something to be swallowed“). It was the Roman scholar Pliny (23-79 CE–who first coined the word “pilula.“

 

Some early pills still exist in museums, such as a famous one dating from 500 BCE. that was known as Terra Sigillata–consisting of clay from a particular island that was mixed with goat’s blood then shaped into pills. Terra Sigillata was supposedly good for practically every ailment, including dysentery, ulcers and gonorrhea. A pill was originally defined as a small, round, solid pharmaceutical oral dosage form of medication. The oldest known pills were made of the zinc carbonates hydrozincite and smithsonite. The pills were used for sore eyes, and were found aboard a Roman ship Relitto del Pozzino which wrecked in 140 BCE. Today, pills include tablets, capsules, and variants thereof like caplets ? essentially any solid form of medication, colloquially falls into the pill category. There are pieces of ancient Roman pill-making equipment, such as a carved stone in the British Museum. The stone has long flat grooves into which the pill maker would press clay or other substances to make long, snaky strings. Then the pill maker would pry the strings out and cut them into discs to form pills–much the way one cuts dough for cookies.

 

During the Middle medieval times, people would coat their pills with slimy plant substances and other materials so they were easier to swallow and tasted less bitter. Some pills were rolled in spices, and later pills began to be coated with gold and silver. Silver, unfortunately, rendered the pills pretty inert, since they’d pass right through the digestive tract without releasing any of their medicinal compounds. Gilding of pills, continued well into the 19th century. Medicines in pill form were popular in 17th century England and thereafter. Pill manufacturers were granted special patent rights from the king for their top-secret formulas. One famous patented product from the 18th century: “Hooper’s Female Pills,“ which were guaranteed to contain “the best purging and anti-hysterik ingredients.“ And pills, of course, made their way over to the still-new United States–which had its own set of patent-protected preparations, courtesy of the U.S. Patent office–including Chase’s Kidney-Liver Pills, Cheeseman’s Female Regulating Pills and Williams’ Pink Pills for Pale People.

 

The old-fashioned, roll-and-cut kinds of pills had a drawback: Their preparation required moisture. Early researchers, (doctors) were learning that this moisture could de-activate the drugs contained. In the 1800s, innovators began sugar-coating and gelatin-coating pills. At this time gelatin capsules were invented, as well as the ability to compress tablets. In 1843, English scientist, William Brockedon invented a different pill form. Powder was placed in a tube and then compressed with a mallet, until it solidified. Eventually, this invention became popular. Holloway’s Pills were perhaps the most famous of the patent medicines, and were popular enough to make Thomas Holloway a wealthy man. Testimonials to the value of the pills can be found at this time, in newspapers all over the British Empire, including Indian, Australia and the North American colonies. The range of diseases the pills claimed to cure is astonishing. Along with Holloway’s Ointment, Holloway’s Pills could treat almost anything. Analysis of the pills showed that they contained aloe, myrrh, and saffron. While probably not harmful, these pills would be unlikely to have the claimed affects. The Holloway advertising changed from time to time, listing a variety of dangers that the pills could prevent. An example, for “Children’s Complaints“:

 

“It is not generally known, but such is the fact that children require medicine oftener than their parents. Three-fourths of the children die before they attain the age of eight years. Let their

mothers, then, be wise, and give to their children small doses of these invaluable pills once or twice every week… The gross humors that are constantly floating about in the blood of children, the forerunners of so many complaints, will thus be expelled, and the lives of thousands saved and preserved to their parents.“

 

Pills have always been difficult to swallow and efforts long have been made to make them go down easier. In medieval times, people coated pills with slippery plant substances. Another approach, used as recently as the 19th century, was to gild them in gold and silver, although this often meant that they would pass through the digestive tract with no effect. In the 1800s sugar-coating and gelatin-coating was invented, as were gelatin capsules. In 1843, the British painter and inventor William Brockedon was granted a patent for a machine capable of “Shaping Pills, Lozenges and Black Lead by Pressure in Dies“. The device was capable of compressing powder into a tablet without use of an adhesive. In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders segregate during manufacturing operations due to different densities, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity but granulation should prevent this. Content uniformity ensures that the same API dose is delivered with each tablet. Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, a pharmacologically inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl methylcellulose and hydroxyethylcellulose).

 

Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants. Tablets are simple and convenient to use. They provide an accurately measured dosage of the active ingredient in a convenient portable package, and can be designed to protect unstable medications or disguise unpalatable ingredients. Colored coatings, embossed markings and printing can be used to aid tablet recognition. Manufacturing processes and techniques can provide tablets with special properties, for example, sustained release or fast dissolving formulations. Some drugs may be unsuitable for administration by the oral route. For example, protein drugs such as insulin may be denatured by stomach acids. Such drugs cannot be made into tablets. Some drugs may be deactivated by the liver when they are carried there from the gastrointestinal tract by the hepatic portal vein (the “first pass effect“), making them unsuitable for oral use. Drugs which can be taken sublingually are absorbed through the oral mucosa, so that they bypass the liver and are less susceptible to the first pass effect. The oral bioavailability of some drugs may be low due to poor absorption from the gastrointestinal tract. Such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or that have severe side effects, the oral route may not be suitable. For example, salbutamol, used to treat problems in the respiratory system, can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action. A proportion of the population have difficulties swallowing tablets either because they just don’t like taking them or because their medical condition makes it difficult for them (dysphagia, vomiting). In such instances it may be better to consider alternative dosage form or administration route.

 

Tablets can be made in virtually any shape, although requirements of patients and tableting machines mean that most are round, oval or capsule shaped. More unusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems. Tablet diameter and shape are determined by the machine tooling used to produce them – a die plus an upper and a lower punch are required. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don’t break up in the bottle, yet friable enough that they disintegrate in the gastric tract. Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist and patient. The mechanical strength of tablets is assessed using a combination of (i) simple failure and erosion tests, and (ii) more sophisticated engineering tests. The simpler tests are often used for quality control purposes, whereas the more complex tests are used during the design of the formulation and manufacturing process in the research and development phase. Standards for tablet properties are published in the various international pharmacopeias (USP/NF, EP, JP, etc.). The hardness of tablets is the principle measure of mechanical strength. Hardness is tested using a tablet hardness tester. The units for hardness have evolved since the 1930s, but are commonly measured in kilograms per square centimeter. Models of tester include the Monsanto (or Stokes) Hardness Tester from 1930, the Pfizer Hardness Tester from 1950, the Strong Cob Hardness Tester and the Heberlain (or Schleeniger) Hardness Tester.

 

Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall, as well as between granules, which helps in uniform filling of the die. Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules. In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a sufficiently homogenous mix of the components cannot be obtained with simple blending processes, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to granulate powders for compression into a tablet: wet granulation and dry granulation. Powders that can be mixed well do not require granulation and can be compressed into tablets through direct compression.

 

Combined oral contraceptive pills were nicknamed “the pill“ in the 1960s

__________________________________________________________________

 

https://www.pinterest.com/nanherriman/19th-century-medicine/

 

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Study Identifies Essential Genes for Cancer Immunotherapy

 

According to a study published online in Nature (7 August 2017), genes have been identified that are necessary in cancer cells for immunotherapy to work. These results address the problem of why some tumors don’t respond to immunotherapy or respond initially but then stop as tumor cells develop resistance to immunotherapy.

 

Cancer immunotherapy relies on T cells, a type of cell in the immune system, to destroy tumors. The authors have previously shown that the infusion of large numbers of T cells can trigger complete regression of cancer in patients, and that T cells can directly recognize and kill tumor cells. However, some tumor cells are resistant to the destruction unleashed by T cells.

 

To investigate the basis for this resistance, the authors sought to identify the genes in cancer cells that are necessary for them to be killed by T cells. Working with a melanoma tumor cell line, the authors used a gene editing technology called CRISPR that “knocks out,“ or stops the expression, of individual genes in cancer cells. By knocking out every known protein-encoding gene in the human genome and then testing the ability of the gene-modified melanoma cells to respond to T cells, the authors identified more than 100 genes that may play a role in facilitating tumor destruction by T cells. Once the authors identified these “candidate“ genes, they sought additional evidence that these genes play a role in susceptibility to T cell-mediated killing. To this end, they examined data on “cytolytic activity,“ or a genetic profile that shows cancer cells are responding to T cells, in more than 11,000 patient tumors from The Cancer Genome Atlas, a collaboration between NCI and the National Human Genome Research Institute, also part of NIH. Results showed that a number of the genes identified in the CRISPR screen as being necessary for tumor cells to respond to T cells were indeed associated with tumor cytolytic activity in patient samples. One such gene is called APLNR. The product of this gene is a protein called the apelin receptor. Although it had been suspected to contribute to the development of some cancers, this was the first indication of a role in the response to T cells. Further investigation of tumors from patients resistant to immunotherapies showed that the apelin receptor protein was nonfunctional in some of them, indicating that the loss of this protein may limit the response to immunotherapy treatment.

 

According to the authors, the results show that many more genes than were originally expected play a vital role in dictating the success of cancer immunotherapies. The authors also noted that this gene list could serve as a blueprint to study the emergence of tumor resistance to T cell-based cancer therapies, and that if this set of genes is validated in clinical trials, then this data could eventually lead to more effective treatments for patients.

 

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Obesity During Pregnancy May Lead to Fetal Overgrowth

 

Macrosomia, or large body size at birth, is common among children born to obese women, particularly those who have gestational diabetes (high blood sugar during pregnancy). Macrosomia also increases the risk that an infant will experience bone fracture during delivery, as well as the likelihood that the infant will need to be delivered by cesarean section. Having a large infant also increases a mother’s risk for postpartum hemorrhage, or excessive bleeding at birth.

 

According to an article published in JAMA Pediatrics (13 November 2017), obesity during pregnancy — independent of its health consequences such as diabetes — may account for the higher risk of giving birth to an atypically large infant.

 

In the current study, researchers analyzed ultrasound scans taken throughout pregnancy of more than 2,800 pregnant women: 443 obese women with no accompanying health conditions, such as diabetes, and more than 2300 non-obese women. The researchers categorized the women’s weight according to their body mass index (BMI) score. Women with a BMI ranging from 30 to 44.9 were classified as obese, while those with a BMI of <29.9 were considered non-obese.

 

Results showed that beginning in the 21st week of pregnancy, ultrasound scans revealed that for fetuses of obese women, the femur (thigh bone) and humerus (upper arm bone) were longer than those of the fetuses of non-obese women. The differences between fetuses of obese and non-obese women continued through the 38th week of pregnancy. For fetuses in the obese group, the average femur length was 0.8 millimeters longer (about 0.03 inches), compared to the non-obese group, and humerus length was about 1.1 millimeters longer (about 0.04 inches), compared to the non-obese group. Average birth weight was about 100 grams (about 0.2 pounds) heavier in the obese group. Moreover, infants born to obese women were more likely to be classified as large for gestational age (birth weight above the 90th percentile), compared to infants born to non-obese women.

 

The study could not determine exactly why the fetuses of obese women were larger and heavier than fetuses in the non-obese group. The authors theorized that because obese women are more likely to have insulin resistance (difficulty using insulin to lower blood sugar), higher blood sugar levels could have promoted overgrowth in their fetuses. The authors also pointed out that earlier studies have indicated that the higher risk of overgrowth seen in newborns of obese women may predispose these infants to obesity and cardiovascular disease later in life. They called for additional studies to follow the children born to obese women to determine what health issues they may face.

 

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FDA Launches Comprehensive Regenerative Medicine Policy Framework

 

The FDA has announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. The framework, which is outlined in a suite of four guidance documents, builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. Further, two of the guidance documents propose an efficient, science-based process for helping to ensure the safety and effectiveness of these therapies, while supporting development in this area. The suite of guidance documents also defines a risk-based framework for how the FDA intends to focus its enforcement actions against those products that raise potential significant safety concerns. This proposed framework is intended to balance the agency’s commitment to safety with mechanisms to drive further advances in regenerative medicine so innovators can bring new, effective therapies to patients as quickly and safely as possible. The policy also delivers on important provisions of the 21st Century Cures Act.

 

The framework includes two final guidance documents and two draft guidance documents.

 

New Final Guidance Documents

 

The two final guidance documents clarify the FDA’s interpretation of the risk-based criteria manufacturers use to determine whether a product is subject to the FDA’s premarket review. The first guidance provides greater clarity around when cell and tissue-based products would be excepted from the established regulations if they are removed from and implanted into the same individual within the same surgical procedure and remain in their original form. The second final guidance helps stakeholders better understand how existing regulatory criteria apply to their products by clarifying how the agency interprets the existing regulatory definitions “minimal manipulation“ and “homologous use.“

 

As this field advances, the FDA has noted that there are a growing number of regenerative medicine products subject to FDA premarket authorization. These guidance documents will help explain how the FDA will provide a risk-based framework for its oversight. The policy framework defines how we intend to take action against unsafe products while facilitating continued innovation of promising technologies. To accomplish this goal, the guidance document has clarified the FDA’s view of “minimal manipulation“ and “homologous use.“ These are two concepts that are defined in current regulation to establish the legal threshold for when a product is subject to the FDA’s premarket approval requirements. By further clarifying these terms in the final guidance, the FDA is applying a modern framework for its oversight. Under the new policy, in order to allow manufacturers of products time to comply with the requirements, for the first 36 months following issuance of the final guidance document the FDA intends to exercise enforcement discretion for certain products that are subject to the FDA’s premarket review under the existing regulations, but are not currently meeting these requirements. The FDA does not intend to exercise such enforcement discretion for those products that pose a potential significant safety concern. Going forward, the FDA will apply a risk-based approach to enforcement, taking into account how products are being administered as well as the diseases and conditions for which they are being used. This risk-based approach allows product manufacturers time to engage with the FDA, as to determine if they need to submit a marketing authorization application and, if so, submit their application to the FDA for approval.

 

New Draft Guidance Documents

 

The two draft guidances provide important information to help spur development and access to innovative regenerative therapies. The first draft guidance, which builds off the regenerative medicine provisions in the 21st Century Cures Act, addresses how the FDA intends to simplify and streamline its application of the regulatory requirements for devices used in the recovery, isolation, and delivery of regenerative medicine advanced therapies (RMATs), including combination products. The guidance specifies that devices intended for use with a specific RMAT may, together with the RMAT, be considered to comprise a combination product.

 

The second draft guidance describes the expedited programs that may be available to sponsors of regenerative medicine therapies, including the new Regenerative Medicine Advanced Therapy (RMAT) designation created by the 21st Century Cures Act, Priority Review, and Accelerated Approval. In addition, the guidance describes the regenerative medicine therapies that may be eligible for RMAT designation – including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, as well as gene therapies that lead to a durable modification of cells or tissues (including genetically modified cells).

 

Both draft guidance documents will have 90-day comment periods.

 

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Adaptation of Lebanese Fattoush Salad with Grilled Haloumi

After adapting this Lebanese salad to available produce, and adjusted to our taste, I have come up with one of the most delicious and refreshing salads, we have had in a long time. Easy to make and beautiful to serve. ©Joyce Hays, Target Health Inc.

 

Most of these ingredients are easy to find, if not, I’ve given substitutes. The haloumi cheese is available at Amazon and Zabar’s. ©Joyce Hays, Target Health Inc. 

 

Fattoush (also fattush, fatush, fattoosh, and fattouche) is a Levantine bread salad made from toasted or fried pieces of Arabic flat bread combined with mixed greens and other vegetables, such as radishes and tomatoes. Fattush belongs to the family of dishes known as fattat (plural of fatteh), which use stale flatbread as a base.

 

Fattoush includes vegetables and herbs according to season and taste. The vegetables are cut into relatively large pieces compared to tabbouleh which requires ingredients to be finely chopped. Staghorn sumac is usually used to give fattoush its sour taste.

 

I decided not to make croutons out of the pita or flat bread. Instead, I served warm pita at the table, with garlic hummus. Although I like to use ground sumac in other dishes, I didn’t want a sour taste in this salad, so omitted the sumac.

 

Ingredients

1 large green capsicum (pepper) or avocado, cut in cubes

1 Lebanese, or long English cucumber, finely chopped

2 ripe truss or vine tomatoes, finely chopped

1/2 red onion, finely chopped

1/2 bunch fresh parsley, leaves chopped

1/2 bunch fresh coriander, leaves chopped

2 pita bread toasted, then make small croutons in food processor

1/4 to 1/2 pound haloumi cheese, cubed (or muenster)

Zest of 1/2 lemon

Juice of 1/2 lemon

 

Dressing 

1/4 cup extra virgin olive oil

1 pinch chili flakes

2 Tablespoons lemon juice

3 small garlic cloves, crushed or squeezed

1/2 teaspoon caster sugar

 

Using a garlic press, you can squeeze the garlic right into a small bowl with the other dressing ingredients. ©Joyce Hays, Target Health Inc.

  

Directions

1. Rinse all of your raw veggies well. You don’t know where they’ve come from or who has handled them. Also, there could be residue from pesticides, even though the claim is organic. Why take a chance, when it only takes a few minutes.

2. Do all of your chopping, cutting slicing, squeezing, peeling etc.

3. Make the dressing first. Simply combine all the ingredients into a small bowl, as you see above.

 

Something so-o refreshing about the smell of chopped cucumbers. ©Joyce Hays, Target Health Inc.

 

Do all of your chopping first. ©Joyce Hays, Target Health Inc.

 

4. If you plan to toast pita or flat bread, do that now. Then, either cut the toasted bread into cubes, or put into food processor and pulse, until you get the size of crouton you want to put into the salad. I have no photos to show re: bread, because decided not to have bread in this kind of salad.

5. In a large salad bowl, that you plan to use for serving, add all of the salad (veggies plus herbs) ingredients, in no special order, and toss them.

 

Making this salad made me feel really healthy; eating it was even better and such a pleasure. You’re going to love this salad. ©Joyce Hays, Target Health Inc.

 

Not a chore; rather, time well spent! ©Joyce Hays, Target Health Inc.

 

You decide if you want to fry the cheese or simply add the cheese cubes to the salad. Do this step last, add the cheese cubes to the salad and give one last toss. I didn’t fry the cheese. ©Joyce Hays, Target Health Inc.

 

I added the dressing last, after adding the cheese cubes. Then several good tosses. ©Joyce Hays, Target Health Inc.

 

6. After tossing the fresh ingredients, add the toasted pita to the salad, if you want to.

7. If you decide to fry the cheese, heat a non-stick frying pan over medium-high heat. Cook the haloumi or muenster, turning, for 2 minutes or until golden. Arrange over the salad. Serve drizzled with a little extra lemon juice.

 

©Joyce Hays, Target Health Inc.

 

We had this salad with warm pita, hummus and well chilled white wine. Then a new recipe I’m working on, curried quinoa with chicken thighs, toasted pistachios, golden raisins. Just about ready to share with you

For dessert, a simple fresh berry combo, photo below.

 

Fresh berry combo for dessert. ©Joyce Hays, Target Health Inc.

 

Varieties of Arab salad: Arab salad, Fattoush, Palestinian salad, Matbucha, Tabbouleh and Raheb. Source: Wikipedia Commons.

 

Pouilly-Fuisse has become our default white wine, taking the place of sauvignon blanc and pinot grigio.

 

We have been following the work of Rajiv Joseph for many years. This weekend we saw his latest play, Describe the Night, produced by one of the theaters we are proud to be patrons of, The Atlantic Theater Company on West 20th Street, here in Manhattan. YOU CANNOT MISS THIS WONDERFUL PRODUCTION WHICH IS RAJIV JOSEPH’S BEST! This is an epic drama based on the life and writings of the great Russian-Jewish, playwright and author, Isaak Babel (1894-1940), who was executed by Stalin’s secret police in 1940. His work was not published in its original versions again, until the 1990s. Babel’s diary becomes a focal point, around which this drama unfolds and weaves around, going, very affectively, back and forth in time. This play is so well acted and directed, that it catches the audience’s attention, immediately, and doesn’t let it go until the final scene. During the two intermissions, we all said agreed (members of audience) that we couldn’t wait to see what would happen next. Certain years of Soviet and Russian history are well integrated into this amazing play.

The sets are excellent and so is the sound design. Be prepared for one of the best theatrical experiences of the year, as Rajiv Joseph expertly traces the stories of seven men and women connected by history, myth and conspiracy theories.

 

Playwright, Rajiv Joseph

Photo credit: Jessica Johnston – Nefariouschafe, CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=17945095

 

Isaak Babel

More about Isaak Babel

Hope you had a great week!

 

From Our Table to Yours

Bon Appetit!

 

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Experiments conducted on worms, zebrafish, mice and, finally, on human subjects in a limited clinical trial conclude that pimozide may be effective in treating what’s known as ‘Lou Gehrig’s disease’

Date:
November 16, 2017

Source:
University of Montreal Hospital Research Centre (CRCHUM)

Summary:
A drug used to treat schizophrenia has the potential to slow the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which there is currently no effective cure. After six years of research on several animal models and a few patients, researchers discovered that pimozide stabilizes the disease in the short term. A clinical trial must confirm the efficacy and safety of the drug before it is offered to patients.

 

Experiments conducted on worms, zebrafish, mice and, finally, on human subjects in a limited clinical trial conclude that pimozide may be effective in treating what’s known as “Lou Gehrig’s disease.”
Credit: Alex Parker and Pierre Drapeau

 

 

Researchers from the University of Montréal Hospital Research Centre (CRCHUM) and the Cumming School of Medicine (CSM) at the University of Calgary have discovered a medication that could make it possible to treat individuals with amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

An article published today in JCI Insight concludes that pimozide was found to be safe and over the short term, preliminary data shows that it could stabilize the progression of ALS. This neurodegenerative disease normally leads to a progressive paralysis of the skeletal muscles and, on average, three years after the onset of symptoms, to death.

“This medication alleviates the symptoms of ALS in animal models,” said Alex Parker, a CRCHUM researcher and professor at Université de Montréal. “Riluzole and edaravone, the drugs currently used, have modest effects. Other studies must be conducted to confirm our results, but we believe that we’ve found a medication that may prove to be more effective in improving patients’ quality of life.”

From worm to man

The story behind the discovery began six years ago with a little millimeter-long nematode worm called C. elegans. In his laboratory, Parker genetically modified the worms so that they would exhibit aspects of the human form of ALS. Simultaneously, his colleague Pierre Drapeau did the same thing to another animal, the zebrafish, a tiny tropical fish only 5 centimetres long.

The two scientists obtained funding from the U.S. Department of Defense to test medications on these worms and fish born with ALS. “We sifted through a library of 3,850 molecules approved for the treatment of other diseases, and found a class of antipsychotic drugs that stabilize mobility in worms and fish,” said Drapeau, a CRCHUM researcher, professor at Université de Montréal and principal investigator on the study. “Pimozide works especially well in preventing paralysis in fish by preserving the neuromuscular junction.”

Subsequently, Université de Montréal Professor Richard Robitaille performed electrophysiological tests on mice in his laboratory and reached the same conclusion. Thus, pimozide was shown to maintain neuromuscular function in three different animal models: worms, fish and mice.

At the annual ALS Canada Research Forum in 2012, the researchers met Dr. Lawrence Korngut, an Associate Professor at the CSM, member of the Hotchkiss Brain Institute (HBI) and Director of the Calgary ALS/Motor Neuron Disease Clinic. “Pimozide is a drug that has been well-known for 50 years,” the neurologist said. “It was approved for treating certain types of psychiatric conditions, like schizophrenia, and costs only 9 cents per pill. Other recent studies have shown genetic links between schizophrenia and ALS. The next logical step was to test it on human volunteers with ALS.”

In 2015, the first preclinical trial for ALS was launched in Canada with a small group of 25 patients who had ALS. Funding was provided by the Quirk family of Calgary, by the HBI, and the Clinical Research Unit at UCalgary.

“We found the highest dose most likely to be tolerated in individuals with ALS — a lower dose than that used in other conditions — and we have preliminary proof showing that pimozide may be useful,” said Korngut.

The initial clinical trial was modest in scope. But after only six weeks, the researchers had a first indication of the drug’s efficacy. Loss of control of the thenar muscles, located in the palm of the hand between thumb and index finger, is usually one of the first signs of ALS. For patients who took pimozide, this function remained stable. This observation is tempered by the very limited size and length of the clinical trial.

“For us, this is an indication that we found the right therapeutic target,” said Drapeau. “Pimozide acts directly on the neuromuscular junction, as shown in our animal models. We don’t yet know whether pimozide has a curative effect, or whether it only preserves normal neuromuscular function to at least stabilize the disease. This is also the first time that a potential drug for human patients was discovered based on basic research on small organisms such as worms and fish.”

Now comes the next step: a phase II clinical trial on 100 volunteers, funded by the “The Ice Bucket Challenge” through a partnership between ALS Canada and Brain Canada to begin in the next few weeks. Headed by Korngut in Calgary and conducted in nine hospital centres across Canada, the study aims to confirm that pimozide is safe and to measure, over a six-month period, its effect on the progression of the disease and its symptoms and on patients’ quality of life.

Daniel Rompré, 47, father of two teenage girls, hopes to participate in the new study. He was diagnosed with ALS in March 2016. The muscles of his upper body are getting weaker, he is beginning to have trouble speaking, and he can no longer use his left arm. “It is hard to maintain a positive outlook,” Rompré said. “You ask yourself: ‘Why me?’ But at least it’s encouraging to see that research is advancing. There has been more progress in the last five years than in 100 years of research on the disease.”

It is too soon to draw firm conclusions about the safety and efficacy of pimozide. “At this stage, people with ALS should not use this medication,” Korngut emphasized. “We must first confirm that it is really useful and safe in the longer term. It is also important to be aware that pimozide is associated with significant side effects. Therefore, it should only be prescribed in the context of a research study.”

Story Source:

Materials provided by University of Montreal Hospital Research Centre (CRCHUM)Note: Content may be edited for style and length.


Journal Reference:

  1. Shunmoogum A. Patten, Dina Aggad, Jose Martinez, Elsa Tremblay, Janet Petrillo, Gary A.B. Armstrong, Alexandre La Fontaine, Claudia Maios, Meijiang Liao, Sorana Ciura, Xiao-Yan Wen, Victor Rafuse, Justin Ichida, Lorne Zinman, Jean-Pierre Julien, Edor Kabashi, Richard Robitaille, Lawrence Korngut, J. Alexander Parker, Pierre Drapeau. Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosisJCI Insight, 2017; 2 (22) DOI: 10.1172/jci.insight.97152

 

Source: University of Montreal Hospital Research Centre (CRCHUM). “Discovery of a promising medication for amyotrophic lateral sclerosis (ALS): Experiments conducted on worms, zebrafish, mice and, finally, on human subjects in a limited clinical trial conclude that pimozide may be effective in treating what’s known as ‘Lou Gehrig’s disease’.” ScienceDaily. ScienceDaily, 16 November 2017. <www.sciencedaily.com/releases/2017/11/171116104804.htm>.

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