The scientific collaborative–led by Sarah Moffitt, PhD, from the UC Davis Bodega Marine Laboratory and Coastal and Marine Sciences Institute–analyzed more than 5,400 invertebrate fossils, from sea urchins to clams, within a sediment core from offshore Santa Barbara, California.
“In this study, we used the past to forecast the future,” says Roopnarine, Academy curator of invertebrate zoology and geology. “Tracing changes in marine biodiversity during historical episodes of warming and cooling tells us what might happen in years to come. We don’t want to hear that ecosystems need thousands of years to recover from disruption, but it’s critical that we understand the global need to combat modern climate impacts.”
The tube-like sediment core is a slice of ocean life as it existed between 3,400 and 16,100 years ago, and provides a before-and-after snapshot of what happened during the last major deglaciation–a time of abrupt climate warming, melting polar ice caps, and expansion of low oxygen zones in the ocean. The new study documents how long it has historically taken for ecosystems to begin recovery following dramatic shifts in climate.
Previous marine sediment studies reconstructing Earth’s climatic history rely heavily upon simple, single-celled organisms called Foraminifera. This week’s study explores multicellular life–in the form of invertebrates–in pursuit of a more complete picture of ocean ecosystem resilience during past periods of climate change.
“The complexity and diversity of a community depends on how much energy is available,” says Roopnarine. “To truly understand the health of an ecosystem and the food webs within, we have to look at the simple and small as well as the complex. In this case, marine invertebrates give us a better understanding of the health of ecosystems as a whole.”
The study’s all-important sediment core revealed an ancient history of abundant, diverse, and well-oxygenated seafloor ecosystems, followed by a period of oxygen loss and warming that seems to have triggered a rapid loss of biodiversity. The study reports that invertebrate fossils are nearly non-existent during times of lower-than-average oxygen levels.
Moffitt emphasized the importance of using a large, 30-foot core sample from one portion of the seafloor, saying the team “cut it up like a cake” to analyze the full, unbroken record.
In periods of fewer than 100 years, oceanic oxygen levels decreased between 0.5 and 1.5 mL/L. Sediment samples during these periods show that relatively minor oxygen fluctuations can result in dramatic changes for seafloor communities.
‘New normal’ of rapid climate change
The study results suggest that future periods of global climate change may result in similar ecosystem-level effects with millennial-scale recovery periods. As the planet warms, scientists expect to see much larger areas of low-oxygen “dead zones” in the world’s oceans.
“Folks in Oregon and along the Gulf of Mexico are all-too-familiar with the devastating impacts of low-oxygen ocean conditions on local ecosystems and economies,” says Roopnarine. “We must explore how ocean floor communities respond to upheaval as we adapt to a ‘new normal’ of rapid climate change. We humans have to think carefully about the planet we are leaving for future generations.”
- Sarah E. Moffitt, Tessa M. Hill, Peter D. Roopnarine, and James P. Kennett.Response of seafloor ecosystems to abrupt global climate change. PNAS, 2015 DOI: 10.1073/pnas.1417130112
California Academy of Sciences. “Climate-related disruptions of marine ecosystems: Decades to destroy, millennia to recover.” ScienceDaily. ScienceDaily, 30 March 2015. <www.sciencedaily.com/releases/2015/03/150330163347.htm>.
Risk-based Monitoring at Target Health
This past week, Dr. Mitchel presented a talk entitled: Impact of Risk-Based Monitoring and eSource Methodologies on Clinical Sites, Patients, Regulators and Sponsors. Respond to the newsletter if you want a copy of the slides. We showed that RBM tied in with eSource methodologies can:
1. At minimum, reduce in half the number of site visits
2. Reduce queries
3. Basically eliminate the need for formal source document verification (SDV) to verify transcription accuracy
4. Replace SDV with source document review (SDR) aka, intelligent monitoring.
Cherry Blossoms in North Carolina – Not in NYC Yet
Couldn’t resist the blossoms in the trees of our parking lot here after work. Light was beautiful, sufficient and diffused by a thin layer of clouds. James Farley, Director, Data Management and Programming, TransTech Pharma, LLC
Cherry Blossoms in NC ©JFarley Photograph 2015
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. 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
Cancer Solutions in Singapore
These are CT scans for two people found to have a left kidney tumor. The patient on the left has a poorly defined mass (radiologists typically describe it as infiltrative) while the one has the right has a well defined solid tumor. The tumor on the left was biopsied and found to be lymphoma. Johns Hopkins Website
Researchers and doctors at the Institute of Bioengineering and Nanotechnology (IBN), Singapore General Hospital (SGH) and National Cancer Centre Singapore (NCCS) have co-developed the first molecular test kit that can predict treatment and survival outcomes in 1) ___cancer patients. This breakthrough was reported in European Urology. According to IBN Executive Director Professor Jackie Y. Ying, By combining our expertise in molecular diagnostics and cancer research, we have developed the first 2) ___ test to help doctors prescribe the appropriate treatment for kidney cancer patients based on their tumor profile. The study was conducted retrospectively with tissue 3) ___collected from close to 280 clear cell renal cell carcinoma (ccRCC) patients who underwent surgery at SGH between 1999 and 2012. Dr. Min-Han Tan, who is IBN Team Leader and Principal Research Scientist and a visiting consultant at the Division of Medical Oncology NCCS, shared his motivation, As a practicing oncologist, I have cared for many patients with kidney cancer. I see the high costs of cancer care, the unpredictable outcomes and occasional futility of even the best available 4) ___. This experience inspired our development of this assay to improve all these for patients. High quality tissue samples are crucial in achieving significant findings in biomedical research. As an Academic Medical Center, we wish to promote the translation of research into advances in healthcare and personalized 5) ___. The development of this test kit for patient care, utilizing the robust tissue archive that we have at SGH, is a good example of this, said Professor Tan Puay Hoon, Head and Senior Consultant, Department of Pathology, SGH.
Kidney 6) ___ is among the ten most frequent cancers affecting men in Singapore, according to The Singapore Cancer Registry (2009-2013). The most common type of kidney cancer is clear cell renal cell carcinoma. Treatment options include surgery, ablation or removal of the tumor, or targeted therapy to shrink or slow the growth of the cancer. The latter works by blocking the growth of new 7) ___ vessels (angiogenesis) or important proteins in cancer cells (tyrosine kinase) that nourish the tumors and help them survive. According to Dr. Min-Han Tan, There are currently about 250 new patients diagnosed with kidney cancer per year in Singapore. Outcomes can be very different. Some patients can be observed for years on end, some benefit from immediate treatment including surgery or targeted therapy, and for some patients, treatment can be futile. Experience is required in making the right judgment for patients. We hope our assay will play a role in helping that judgment.
Targeted drugs are prescribed routinely for cancer patients. Revenues from anti-angiogenic drugs, such as Sutent® and Nexavar™, are estimated at several billion dollars annually. Such drugs, however, are not only expensive but may cause 8) ___ effects in patients, including fatigue, loss of appetite, nausea, diarrhea, pain, high blood pressure, bleeding and heart problems. Due to genetic variations, individual patients respond differently to these drugs and have different survival outcomes. As a result, pharmaceutical companies and academic institutions have invested heavily in seeking out tools and biomarkers to predict personalized outcomes with these therapies, and the development of a reliable anti-angiogenic predictor would be of significant interest to them. Extensive molecular characterization of ccRCC by the team and other researchers worldwide in recent studies has suggested the existence of specific subtypes with different survival outcomes. The researchers therefore set out to discover reliable biomarkers that could improve the prognostic prediction, and identify patients who would be likely to benefit from one type of 9) ___. For this purpose, the team designed a practical assay for studying/diagnosing real-world tumor samples from ccRCC patients. The assay was able to distinguish patients into groups of different survival and treatment outcomes. This is one of the first assays capable of predicting outcomes of anti-angiogenic therapy, a key goal for cancer care and industry. Dr. Tan added, Our diagnostic assay successfully classified ccRCC into groups correlating to different survival and treatment outcomes. This allows patients and to make more educated choices in their treatment options. Additionally, the development of such assays in Singapore demonstrates the highest levels of research, care and expertise that are available to our patients here. This test has been validated at the Singapore General Hospital and National Cancer Centre Singapore. Source: A*STAR in Singapore; Yukti Choudhury, Xiaona Wei, Ying-Hsia Chu, Lay Guat Ng, Hui Shan Tan, Valerie Koh, Aye Aye Thike, Eileen Poon, Quan Sing Ng, Chee Keong Toh, Ravindran Kanesvaran, Puay Hoon Tan, Min-Han Tan. A Multigene Assay Identifying Distinct Prognostic Subtypes of Clear Cell Renal Cell Carcinoma with Differential Response to Tyrosine Kinase Inhibition. European Urology.
Singapore Researchers Identify Cells That Cause Gastric Cancer
10) ___cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.
A team of scientists led by a researcher from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has identified the cancer specific stem cell which causes gastric cancer. This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers. The research group, led by Dr Chan Shing Leng, Research Assistant Professor at CSI Singapore, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer 11) ___cells but not normal cells. Conceptualized by Dr. Chan and Associate Professor Jimmy So, a Senior Consultant from the Department of Surgery at the National University Hospital Singapore, the study is also the first to be conducted with human gastric tissue specimens and took five years to complete. This novel study was published in the research journal Cancer Research.
How CD44v8-10 serves as a biomarker: Many cancer cell types express high levels of a cell surface protein known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumor relapse. There are many forms of CD44 and the standard form of CD44, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem 12) ___. This is critical as an ideal cancer target should mark only cancer cells but not normal cells. Research in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analyzed 53 patient tissue samples in conjunction with patient-derived xenograft models which are derived from intestinal type gastric cancer. The team is one of the few groups in the world to have a relatively large collection of patient-derived xenograft models for gastric cancer and the first to use these models for identification of gastric cancer stem cells. A total of eight cancer cell lines were used in this study, including six new cell lines which were established. The team discovered a cancer-specific CD44 variant, CD44v8-10 marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumor sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells. As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available and doctors rely on 13) ___ for the screening and diagnosis of this disease. Said Dr Chan, With our findings, we can now work on developing drugs that would recognize and attack the cancer stem cells only, reducing the side effects on normal cells. With additional funding, we aim to have a drug that can show efficacy in our models within three years. We are very excited about this discovery. It may explain why gastric cancer patients develop cancer relapse after chemotherapy as conventional chemotherapy mainly targets the common cancer cells. Hence, if we can find drugs that can target these gastric cancer stem cells, we may improve the patients’ outcome in the future, said Assoc Prof So, who is also a faculty member from the Department of Surgery at the NUS Yong Loo Lin School of Medicine. In the next phase of their research, the team aim to develop an antibody drug that targets CD44v8-10. The research team also hopes to establish more patient-derived xenograft models to achieve extensive coverage of the patient spectrum in Singapore as the level of CD44v8-10 varies among patients. These xenograft models play an important role as pre-clinical models for evaluating potential therapeutics that target CD44v8-10. Source: National University of Singapore; W. M. Lau, E. Teng, H. S. Chong, K. A. P. Lopez, A. Y. L. Tay, M. Salto-Tellez, A. Shabbir, J. B. Y. So, S. L. Chan. CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells. Cancer Research
Singapore Study Reduces Toxicities Metastatic Renal Cell Carcinoma: A study led by the Genitourinary (GU) oncology team at National Cancer Centre Singapore (NCCS) has revealed conclusive results in reducing toxicities for Asian patients with metastatic renal cell carcinoma (mRCC) or cancer that has spread beyond the kidney. The seven-year study began in 2007 and the findings revolutionized the standard protocol for patient management in NCCS with an attenuated-dose regimen of sunitinib (Sutent) for patients with mRCC. The new treatment regimen for sunitinib has been accepted by oncologists in Singapore. For the patients, this would mean an estimated 30% reduction in fees because of the lower dosage. The median overall survival rate was 27.4 as compared to 21.8 months among patients receiving the attenuated dosage. Sunitinib was introduced as a treatment for mRCC in Singapore since early 2005. The U.S. FDA approved dosing of sunitinib is 50mg once daily for four weeks, followed by a two-week break in a six-week treatment cycle (conventional-dose regimen). Subsequent findings from 2005 to 2006 show that high toxicities were observed with the conventional dosing, especially in Asians. Many of the patients were experiencing severe side effects of grade 3 or higher with the conventional dosing. Our immediate response was to refine the treatment protocol to improve patients’ quality of 14) ___, explained Dr Tan Min Han, Visiting Consultant, Division of Medical Oncology and member of the GU team, NCCS. NCCS initiated a prospective clinical registry with 127 mRCC patients receiving attenuated sunitinib dosing of 37.5mg/d/4/2 (37.5mg of sunitinib once daily for four weeks, followed by a two-2 week break) as treatment protocol in 2007. Clinical data of patients receiving sunitinib at NCCS from 2005 to 2012 and three other tertiary centres in Singapore (Johns Hopkins-International Medical Centre, National University Hospital Singapore, and Onco-Care of Gleneagles Medical Centre) from 2005 to 2009 were used for comparison, representing at least 90% of all patients with mRCC treated over the period. The data revealed favorable results between the attenuated dosing regimen compared to the conventional dosing. 59% of the participants experienced severe side effects as compared to the previous 85%; 24% than 58% required reduction in dose delays; and 35% rather than 70% of patients requiring dose reduction during their course of treatment. Both dose delays and reduction are only required when high level of toxicities are observed. Dr Tan reiterated the importance of the findings, This is an affirmation to our efforts and we believed that the continuous understanding of real world outcomes will reap greater benefits for our patients. The findings would not be possible without the collaborative nature of our tertiary healthcare counterparts. Source: SingHealth; Hui Shan Tan, Huihua Li, Yu Wen Hong, Chee-Keong Toh, Alvin Wong, Gilberto Lopes, Miah Hiang Tay, Alexandre Chan, Xin Yao, Tiffany Tang, Quan Sing Ng, Ravindran Kanesvaran, Noan Minh Chau, Min-Han Tan. Efficacy and Safety of an Attenuated-Dose Sunitinib Regimen in Metastatic Renal Cell Carcinoma: Results From a Prospective Registry in Singapore. Clinical Genitourinary Cancer
ANSWERS: 1) kidney; 2) genetic; 3) samples; 4) drugs; 5) medicine; 6) cancer; 7) blood; 8) side; 9) treatment; 10) Gastric; 11) stem; 12) cells; 13) endoscopy; 14) life
Lee Kuan Yew (1923-2015)
Lee Kuan Yew in 2002
Lee Kuan Yew passed last week and we celebrate his life and the enormous legacy he left to the world.
On 5 February 2015, Lee was hospitalized with severe pneumonia and was put on a ventilator at the intensive care unit of Singapore General Hospital, although his condition was reported as stable. A 26 February update stated that he was again being given antibiotics, while being sedated and still under mechanical ventilation. From 17 to 22 March, Lee continued weakening as he suffered an infection while on life support, and he was described as critically ill. On 23 March 2015, Singapore’s Prime Minister Lee Hsien Loong announced his father’s death at the age of 91.
Lee, the founding father of modern Singapore and its prime minister from 1959 to 1990, single-handedly was responsible for transforming Singapore into a Western-style economic success. He offers a unique perspective on the geopolitics of East and West. American Presidents from Richard Nixon to Barack Obama have welcomed him to the White House; British prime ministers, Australian, Japanese, Indonesian, Philippine: Margaret Thatcher, Tony Blair, Kevin Rudd, Junichiro Koizumi, Susilo Bambang Yudhoyono, Gloria Macapagal-Arroyo to name a few, recognized his wisdom. Business leaders from Rupert Murdoch to Rex Tillerson, CEO of Exxon Mobil, and all the pharmaceutical companies located in Singapore, have praised his accomplishments.
As Lee Kuan Yew’s health deteriorated over the last month, thousands of Singaporeans visited his hospital and a community center to leave flowers, gifts and emotional messages of support.
At this time of questionable political leaders with their lack of vision and experience, we must acknowledge the passing of a towering giant. Although he ran only a city-state, Lee Kuan Yew, along with late Chinese Premier Deng Xiaoping, ranks among Asia’s most pivotal figures of the past 50 years. These two men – a tall, aristocratic scion of a Hakka trading family and the diminutive Chinese revolutionary – came from very different perspectives, but shared a pragmatic streak, and ultimately strategies that came to be widely copied. You can see their legacy today across the continent, in rapid urbanization and growing economic power. But it was Lee who first formulated the essentials of the new Asian economic approach, blending capitalistic modernity with a state-directed economy and authoritarianism. Although repression of dissidents in both countries rightfully offends Westerners, it has not deterred foreign capital, technology and capital from seeking to cash in on Asia’s growth. American and British capital may have fueled global capitalism’s 20th century triumph, but Lee and Deng shaped its expansion in the 21st.
Lee’s great achievements as prime minister took place from 1959 to 1990, the longest of any leader in world history. The singularity and durability of his accomplishments reveal their greatness and that of his legacy. From Singapore’s independence to the present day, Lee helped fashion what is arguably the most successful and best run city in the world. In 1965, after Singapore’s acrimonious exit from Malaysia, its outlook was far from promising. Unemployment was high and the fledgling city-state was wracked by internal dissension between its ethnic mix of Chinese, Indians and Malays, and between conservatives and communists, who seemed in political ascendancy as elsewhere in Southeast Asia. The then rough-edged Asian metropolis, an important trading center, boasted a per capita GDP of $2,667 in 1990 dollars, more than double the average for East Asian countries and trailing only Japan in the region, but well behind European countries and North America. Faced with imminent disaster, Lee’s response was to create a new political system that blended a mildly socialist program with a development strategy aimed at attracting foreign capital and building up the manufacturing sector. Lee and his People’s Action Party (PAP) focused on developing a modern infrastructure – from the port and roads to education – that is second to none. Perhaps PAP’s most remarkable achievement was the creation of the Housing Development Board, which turned the vast majority of Singaporeans from slum-dwellers to owners of apartments that were small but clean and modern. As Asian real estate markets have heated up, HDB has helped keep Singaporean housing costs far more reasonable than in China’s primary cities, or Hong Kong or Tokyo.
Lee believed widespread homeownership would make Singapore more stable, but it was not enough to make it rich. Under his guidance, everything – from cleaning the streets to developing arguably the best primary education system in the world – was calculated to attract foreign companies and skilled individuals; this at a time when China, India and much of Southeast Asia was either closed to investment, embroiled in lethal civic conflict or primarily dominated by crony capitalists. And the world did come, making Singapore among the favored destinations for international corporations. In 1968 Texas Instruments TXN -1.05% established a chip-making plant there, the break Lee later credited with helping transform the city into a technology hotspot. A 2011 Roland Berger study named Singapore as the leading location for European companies to establish headquarters in the Asia-Pacific region. Companies with regional headquarters include Microsoft, Google, Exxon Mobil, and Kellogg. Singapore now has more than twice as many regional headquarters as far-larger Tokyo, not to mention Asia’s less affluent megacities.
Cambridge-educated, and with the demeanor of a British aristocrat, Lee promoted English as the country’s primary language, a decision that made the city particularly attractive to foreign investors and workers. But in many ways he remained very Chinese. Lee’s People’s Action Party blended British parliamentary forms with a highly authoritarian, centrally directed system. When Deng visited the city-state in 1978, he saw it as an appealing model for his poor country: a top-down, mandarin-led system that could appeal to global capitalists. Deng, Lee would later recall, was most captivated by Singapore’s modern prosperity: What he saw in Singapore in 1978, he recalled in his book Third World to First, had become the point of reference as the minimum the Chinese people should achieve. Anyone visiting China today can see the results of Deng’s insight: gleaming cities, massive expansion of educational institutions, modern roads and transit systems, and most of a general prosperity that has lifted the mother country of most Singaporeans to almost unimagined heights. Although Singapore is generally less repressive than China, it did show the Chinese communists that being free was not necessary for becoming rich. It’s a lesson that many developing countries around the world – in the Middle East, Africa and Latin America – have taken to heart. Urban innovation was great under Lee Kuan Yew. Urban farming with its superior technology, has taken hold, in order to supply its citizens with fresh produce. Another proposal would boost the city-state’s population from 5 million to roughly 7 million by 2030, largely through immigration. To help accommodate this growth, planners have suggested building a vast underground city with shopping malls, public spaces, pedestrian links and cycling lanes. Yet despite these problems, Lee Kwan Yew’s accomplishments are undeniable. He took a struggling, ununified city and left it an urban jewel. That history has moved on is inevitable, but one has to wonder, among all the current chiefs of state, whether any will leave behind anything approaching Lee Kuan Yew’s legacy.
Part of Yew’s great legacy was to give Singapore, legal and economic stability so that companies world-wide would open offices there. Pharmaceutical research and manufacturing. Is one of the industries that has Asian headquarter there. Singapore also brings together a well-developed infrastructure and logistics network, strong intellectual property (IP) laws, a record of safety, a good regulatory environment, and active government support of the biomedical industry. For drug companies looking for an Asian country in which to manufacture pharmaceuticals, expand R&D, or sell their products, Singapore is a good choice. Plus, Singapore has its own pharmaceutical and biotech companies.
The pharmaceutical market in Singapore is valued at almost $1 billion. Singapore has worked to create a solid foundation for the biomedical industry, with over 30 public-sector research institutes under the Ministry of Health (MOH) and the Agency for Science, Technology and Research (A*STAR). These include the Bioinformatics Institute, Genome Institute, Institute of Bioengineering & Nanotechnology, Bioprocessing Technology Institute, Institute of Medical Biology, Institute of Molecular and Cell Biology and the Singapore Institute for Clinical Sciences. Singapore has promoted public-private research institutes – such as with Bayer, Roche, Siena Biotech, Novartis, and GlaxoSmithKline (GSK) – as well as supporting the development of clinical contract research organizations (CROs). The government spent $2 billion investing in biomedical capabilities and infrastructure over the previous decade and earmarked more than $3 billion to support biomedical enterprises and research from 2011-2015. There are a few domestic Singaporean pharmaceutical companies that are also successful in Singapore. For example, A. Menarini Asia-Pacific, formerly Invida, is a pharmaceutical company that was founded in 2005 in Singapore. In addition to its headquarters in Singapore, it has almost a dozen locations in other Asian countries, marketing branded pharmaceuticals, medical devices, and biotechnology to hospitals, pharmacies, and clinics. The company also has partnerships with a variety of multinational drug companies based in the U.S., EU and Japan. More than 30 of the top global biomedical sciences firms – including Novartis, Eli Lilly, Takeda and GSK – have a R&D presence in Singapore. Of the top 10 biopharmaceutical companies, seven manufacture some of their products in Singapore and 8 have regional headquarters in Singapore. GSK, Baxter and Roche all launched their first-in-Asia commercial production facilities in Singapore in 2009. Some companies, such as Merck, Pfizer, Sanofi-Aventis and Abbott, have chosen Singapore as their global manufacturing base. Within 5 years, Singapore will have eight biologics production facilities – worth $2 billion. Foreign biomedical companies spent approximately $500 million on R&D in Singapore last year, up from $40 million a decade ago. Nationally, public and private organizations spend almost $1.2 billion on biomedical R&D every year, with several thousand private- and public-sector researchers. In 2013, biomedical firms in Singapore manufactured products worth $25 billion, up from $5 billion in 2000. This year Novartis and Amgen will open Asian headquarters in Singapore.
Association of Atopic Dermatitis with Overweight and Obesity – Another Reason to Eat Healthy
Atopic dermatitis (AD) is a chronic (long-lasting) disease that affects the skin. It is not contagious and cannot be passed from one person to another. The word dermatitis means inflammation of the skin. Atopic refers to a group of diseases in which there is often an inherited tendency to develop other allergic conditions, such as asthma and hay fever. In AD, the skin becomes extremely itchy. Scratching leads to redness, swelling, cracking, weeping clear fluid, and finally, crusting and scaling. In most cases, there are periods of time when the disease is worse (called exacerbations or flares) followed by periods when the skin improves or clears up entirely (called remissions). As some children with ADs grow older, their skin disease improves or disappears altogether, although their skin often remains dry and easily irritated. In others, AD continues to be a significant problem in adulthood.
AD is often referred to as eczema, which is a general term for the several types of inflammation of the skin. AD is the most common of the many types of eczema. Below is a picture found on the website of the AAD.
Atopic dermatitis: Infants often get atopic dermatitis on their cheeks, as did this 7-month-old boy.
Previous studies found conflicting results about whether AD is associated with overweight/obesity. As a result, a study published in the Journal of the American Academy of Dermatology (2015;72:606-616) was performed to examine the relationship between AD and overweight/obesity by performing a systematic review and meta-analysis. For the study, observational studies of the relationship between AD and overweight/obesity were selected from PubMed, Embase, and the Cochrane Library. The quality of evidence was assessed using the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were performed to estimate pooled odds ratios (ORs). Sensitivity analyses were performed that compared results by location of study, study quality, and between studies in children and adults.
A total of 30 studies were included for review. Patients who were overweight (OR, 1.27), obese (OR, 1.68), or overweight/obese (OR, 1.42), all had higher odds of AD than normal weight patients. In sensitivity analyses, children who were overweight, obese, or overweight/obese and adults who were obese or overweight/obese had higher odds of AD. The association remained significant in North America and Asia but not Europe. The authors concluded that in spite that the most studies were cross-sectional in nature, it could be concluded that overweight/obesity in North America and Asia is associated with an increased prevalence of AD.
Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine
Human noroviruses (NoVs) are the primary cause of acute gastroenteritis. These viruses are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. As a result, a study published online in PLOS Medicine (24 March 2015) used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers.
For the study, sera from 10 human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Results showed that immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997.
While study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated, the authors concluded that vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. In addition, these data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations.
FDA Approves New Treatment for Diabetic Retinopathy in Patients with Diabetic Macular Edema
Congratulations to our friends and colleagues at Regeneron.
Diabetic retinopathy (DR) is the most common diabetic eye disease and is a leading cause of blindness in adults in the United States. According to the Centers for Disease Control and Prevention (CDC), diabetes (type 1 and type 2) affects more than 29 million people in the United States and is the leading cause of new blindness among people ages 20 to 74 years. In 2008, 33% of adults with diabetes aged 40 years or older had some form of DR. In some cases of DR with diabetic macular edema (DME), abnormal new blood vessels grow on the surface of the retina. Severe vision loss or blindness can occur if the new blood vessels break.
The FDA has expanded the approved use for Eylea (aflibercept) injection to treat DR in patients with diabetic macular edema. Eylea is administered by a physician as an injection into the eye once a month for the first five injections and then once every two months. It is intended to be used along with appropriate interventions to control blood sugar, blood pressure and cholesterol.
The safety and efficacy of Eylea to treat DR in patients with DME were evaluated in 679 participants in two clinical studies where participants were randomly assigned to receive Eylea or macular laser photocoagulation, a laser-based treatment used to burn small areas of the retina. At week 100, participants being treated with Eylea showed significant improvement in the severity of their DR, compared to patients who did not receive Eylea. The most common side effects associated with Eylea include bleeding of the conjunctiva (the tissue that lines the inside of the eyelids and covers the white part of the eye); eye pain; cataracts; floaters; increased pressure inside the eye (increased intraocular pressure); and separation of the interior jelly of the eye from the retina (vitreous detachment). Serious adverse reactions include infection within the eye (endophthalmitis) and retinal detachments.
The FDA granted breakthrough therapy designation to Eylea for the treatment of DR with DME. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening conditions. The FDA also reviewed the new use for Eylea under the agency’s priority review program, which provides for an expedited review of drugs that demonstrate the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.
The FDA previously approved Eylea to treat wet (neovascular) age-related macular degeneration, a condition in which abnormal blood vessels grow and leak fluid into the macula. Eylea is also approved to treat DME and macular edema secondary to retinal vein occlusions, both of which cause fluid to leak into the macula resulting in blurred vision.
Eylea is marketed by Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc.
No Guilt Cheese Cake
Crust (I didn’t make it), but go ahead if you don’t mind more calories:
1 1/2 cups crushed graham cracker crumbs
6 Tablespoons melted butter or coconut oil
1/4 cup sugar
3 cups O% fat cottage cheese, with pineapple
2 cups non-fat plain Greek yogurt
3/4 cup Splenda
3/4 cup Agave
1/4 cup almond flour
Zest from one lemon
2-3 teaspoons fresh lemon juice
2 teaspoons vanilla extract
Raspberry Coulis (Sauce) Easy & Low-Cal
Ingredients & Directions
2 cups, quartered, hulled fresh raspberries (or strawberries)
1/4 cup water
2 Tablespoons Agave
1 Tablespoon Splenda
1 Tablespoon fresh lemon juice
1. Combine all ingredients in a blender or food processer and puree until very smooth.
2. Press the puree through a fine mesh strainer to remove any seeds or skin that didn’t puree.
3. Cover and refrigerate until cold. This keeps well and you can make it ahead of time.
4. Spoon it over cheese cake, ice cream or pound cake.
Spray a 9×13 casserole dish with non-stick spray. Bake for 8 minutes in a 350 degrees F. preheated oven. Allow the crust to cool on the counter while making the cheesecake filling.
Add the cottage cheese, yogurt, eggs, and sugar to a blender or food processor. Blend or pulsate until the filling is smooth like cake batter. Add the flour, zest, lemon juice, and vanilla extract. Blend again until smooth.
Pour the filling into oiled, prepared individual ramekin dishes. Place all the ramekins into an aluminum pan with a little water added into the pan and bake for 60 minutes or until the center of the cheesecake is not jiggly. Carefully touch the center of the cheesecake. The texture should feel soft but firm to touch. If the center feels like liquid, continue to cook the cheesecake for 10 more minutes and check again.
Allow the cheesecake to cool. Serve while still a little warm with the raspberry coulis spooned over the cheese cake.
Gather all ingredients ©Joyce Hays, Target Health Inc.
Just Out of the Oven ©Joyce Hays, Target Health Inc.
Stag’s Leap, reliable Vineyard has a wine for all budgets. ©Joyce Hays, Target Health Inc. This is a good year. Their Artemis is good and so is their Fay among many others.
No guinea pig to experiment with this week, as Jules was traveling all week, to DC. Then Vegas, then San Francisco and I made vegan recipes all week and lost over 5 pounds ta da! Eating mainly a chickpea/onion casserole,with sauce made out of yogurt and tahini, plus fresh garnish of tomatoes with cucumber and parsley with fresh mint. Want to know more?
When he returned, back to experimenting. I can share with you a no guilt cheese cake recipe that I accidentally stumbled onto by buying pineapple zero fat cottage, instead of plain zero-fat cottage. This cheese cake tastes best if eaten slightly cooled, then eaten with a bit of the raspberry coulis spooned on top, as you see In the first photo.
Our weekend was haphazard. Has this happened to you? Plan one thing, it doesn’t work. Try something else and oh well. We went to the revival of Steven Sondheim’s, Out Of The Woods. What a gawd awful mess, but the critics liked it. I must be the only New Yorker who does NOT like much of anything Steven Sondheim has created. I can say that I DO like, A Little Night Music, with the lovely song from it, Send InThe Clowns. Other than this, Sondheim productions leave me cold. We walked out of, Sweeny Todd; The Demon Barber of Fleet Street, even though we had the best seats at a gala performance. Just could not stand it. IMO, the show we saw this weekend could not have been more awful. Sets were helter skelter, voices were nothing to speak of, not one memorable song, need I go on? We didn’t walk out, but only lovely red wine and dinner at one of our favorite Italian restaurants could get us back to being relatively amenable. And, finally we had a good time. Interesting how it all gets back to the basics, food and – well, you know!
Spring is supposed to renew us, right? I need renewing, how about you?
Hope Your Week Was A Good One!
But still prefer Sexy Beast cabernet, from Two Hands Vineyard, Australia ©Joyce Hays, Target Health Inc.
From Our Table to Yours!
“We measured temperatures at altitudes of 90 to 140 kilometers,” says an author of the study, Denis Belyaevof MIPT and the Space Research Institute of the Russian Academy of Sciences. “On the night side of the planet, temperatures normally fall with altitude, but we noticed a peak in the chart in the 90 to 100 kilometer range. Here, the atmosphere was 20-40 degrees warmer than we expected. We don’t yet understand what causes the warming, but Venus’ ozone layer is at this altitude. There may be a connection.”
Belyaev, along with his colleagues from MIPT and the Space Research Institute, Anna Fedorova and Oleg Korablev, and researchers from the French laboratory LATMOS, as well as from Belgium, Germany and the U.S. analyzed the data obtained by the SPICAV spectrometer on board Venus Express between June 2006 and February 2013.
The European mission Venus Express was launched from the Baikonur space center in 2005 using the Russian rocket Soyuz-FG. Scientific instruments for the probe were developed by an international team of scientists, including from Russia. The unit was removed from service in February 2015, but scientists continue to analyze the data it obtained throughout its operation.
The SPICAV system (Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Venus) consisted of two spectrometers, an infrared one, created by Russian specialists, and an ultraviolet one, made by French scientists. Atmospheric temperatures were taken in the UV channel using the stellar occultation method, wherein a spectrometer captures the light emitted by a star as it goes behind a planet. The starlight radiates through the planet’s atmosphere, whose characteristics can be retrieved based on the spectrum produced.
The scientists selected stars that shine brighter in ultraviolet, that is, from118 to 320 nanometers, the working range of the spectrometer (there were a total of 50 of them). Each second within the few minutes that the star took to disappear behind the planet’s horizon the spectrometer took a shot of its spectrum. Then the scientists divided the “atmospheric” spectrum by the star’s “clean” spectrum to determine the gas composition and density of the atmosphere at different altitudes, as well as temperatures. From June 2006 to February 2013 they made 587 “shots” of the atmosphere, which covered almost the entire night hemisphere.
“In almost every session of these seven years we detected a layer at altitudes of 90-100 km that is 20-40 kelvins warmer than it should be,” says Belyaev. “The air temperatures at these altitudesare220-240 kelvins, while they should be under 200.”
According to Belyaev, this layer is in the same range of altitudes where the ozone is. “We are carrying out correlation analysis to determine if these are connected or not,” Belyaev said. “We can’t rule out that this phenomenon may be explained by chemical reactions, namely the decomposition of ozone when it comes in contact with chlorine-based substances — these reactions may result in the release of heat.”
The researchers have found yet another peculiarity of Venus’ upper atmosphere: early in the morning it is warmer than in the evening, while it should be the other way round.
Venus is a unique planet in that rotates not in the direction of its movement along the circumsolar orbit, but in the opposite direction, because its rotation axis is tilted 177 degrees. And it rotates very slowly — a solar day on the planet lasts 116 days. During the long night the upper atmosphere cools, so at night it should be warmer than in the morning.
“We found that the atmospheric temperature is 20 degrees warmer in the morning than in the evening,” Belyaev says. “This is probably due to the global circulation of the atmosphere. The transition of the sub-solar point to the anti-solar point takes place at altitudes of about 100 kilometers. In this area on the night side, the air mass goes down to 70 km, which may lead to the adiabatic heating of the atmosphere.”
The researchers continue to study the data collected by Venus Express, hoping to learn new information about the planet.
The work of the Russian scientists was funded through a government megagrant received by MIPT in 2011. The megagrant enabled MIPT to create a laboratory for the infrared spectroscopy of planetary atmospheres in high resolution, headed by Vladimir Krasnopolsky, a research professor at the Catholic University of America.
- Piccialli, A., et al. Thermal structure of Venus nightside upper atmosphere measured by stellar occultations with SPICAV/VenusExpress. Planetary and Space Science, 2015 DOI: 10.1016/j.pss.2014.12.009i
Moscow Institute of Physics and Technology. “Unexplained warm layer discovered in Venus’ atmosphere.” ScienceDaily. ScienceDaily, 25 March 2015. <www.sciencedaily.com/releases/2015/03/150325131714.htm>
Ice crystals form in the beautifully symmetric tetrahedral shapes seen in snowflakes and on the surface of frozen ponds. Such geometries can persist at very high pressures, even if the underlying structure undergoes phase changes both subtle and dramatic with varying pressure. This certainly applies to unconstrained water. When confined between other materials, however, the behaviour of water is influenced by atomic interactions with material surfaces. The more usual ice crystals can then morph into something quite different.
When water is confined at high pressure between sheets of graphene — a single-atom-thick arrangement of carbon atoms in a hexagonal lattice — its molecules adopt a square configuration. This is the surprise finding of researchers in Germany, the UK and China.
Published in the journal Nature, the results of the study, funded in part by the Graphene Flagship, could improve our understanding of water transport through nanometre-scale channels in natural and artificial membranes. For example, the aquaporin protein-mediated flow of water across biological cell membranes is down to a balance between hydrophobic and hydrophilic interactions with channel surfaces. Such interactions are dependent on chemical bonds between hydrogen atoms.
With graphene ‘pores’ the situation is different, in that the cross section is planar rather than circular. Also, the pressure exerted on the water is so high that hydrogen bond interactions with the graphene surface are overcome by the attractive van der Waals atomic interaction that draws together the graphene planes. Still, the comparison is pertinent, and should add to the scientific debate around water flow through nanoscale channels and across membranes.
Ulm University physicists Gerardo Algara-Siller and Ossi Lehtinen carried out the latest experiment, in which a graphene monolayer was first deposited on an electron microscope grid. This graphene layer was then exposed to a small amount of water, and covered with another layer of graphene. Much of the water was squeezed out of the graphene sandwich by the van der Waals force; the remainder was trapped in pockets less than a millionth of a metre across.
“Gerardo Algara-Siller and Ossi Lehtinen carried out the experiment, and imaged the unknown ice structure between graphene sheets,” said Ulm University professor Ute Kaiser, who led the German side of the collaboration. “We did not know at first what we were seeing, and only in discussion with our Manchester colleagues was the idea of square ice born. A detailed structural and elemental analysis then proved this structure to be real.”
The Manchester connection is significant, not least owing to participation in the research by Irina Grigorieva, who has a special interest in molecular and particle transport across membranes formed of layered materials such as graphene. Scientists have long sought to understand the structure and behaviour of water confined within narrow channels. The study has until now only been possible in computer simulations, the results of which seldom agree with each other.
Grigorieva’s Manchester colleague Andre Geim, who shared the 2010 Nobel Prize in Physics for his pioneering work on graphene, is another co-author of the new Naturepaper. Geim and others had previously speculated that observations of ultrafast water flow through graphene nanocapillaries could be due to two-dimensional square ice. The new research appears to confirm the hypothesis, even if the detailed origins of this strange structure remain a mystery.
- G. Algara-Siller, O. Lehtinen, F. C. Wang, R. R. Nair, U. Kaiser, H. A. Wu, A. K. Geim, I. V. Grigorieva. Square ice in graphene nanocapillaries. Nature, 2015; 519 (7544): 443 DOI: 10.1038/nature14295
Graphene Flagship. “New form of ice: Square ice filling for a graphene sandwich.” ScienceDaily. ScienceDaily, 25 March 2015. <www.sciencedaily.com/releases/2015/03/150325140221.htm>.