The role of low-cost robots in the future of spaceflight.

Lessons from the CubeSat and Mars Exploration programs may guide the infusion of robotics for planetary science and exploration.

Simultaneous automated ascertainment of prevalent vertebral fracture and abdominal aortic calcification in clinical practice: role in fracture risk assessment.

Whether simultaneous automated ascertainments of prevalent vertebral fracture (auto-PVFx) and abdominal aortic calcification (auto-AAC) on vertebral fracture assessment (VFA) lateral spine bone density (BMD) images jointly predict incident fractures in routine clinical practice is unclear. We estimated the independent associations of auto-PVFx and auto-AAC primarily with incident major osteoporotic and secondarily with incident hip and any clinical fractures in 11 013 individuals (mean [SD] age 75.8 [6.8] years, 93.3% female) who had a BMD test combined with VFA between March 2010 and December 2017. Auto-PVFx and auto-AAC were ascertained using convolutional neural networks (CNNs). Proportional hazards models were used to estimate the associations of auto-PVFx and auto-AAC with incident fractures over a mean (SD) follow-up of 3.7 (2.2) years, adjusted for each other and other risk factors. At baseline, 17% (n = 1881) had auto-PVFx and 27% (n = 2974) had a high level of auto-AAC (≥ 6 on scale of 0 to 24). Multivariable-adjusted hazard ratios (HR) for incident major osteoporotic fracture (95% C.I.) were 1.85 (1.59, 2.15) for those with compared to those without auto-PVFx, and 1.36 (1.14, 1.62) for those with high compared to low auto-AAC. The multivariable-adjusted HRs for incident hip fracture were 1.62 (95% C.I. 1.26 to 2.07) for those with compared to those without auto-PVFx, and 1.55 (95% C.I. 1.15 to 2.09) for those high auto-AAC compared to low auto-AAC. The 5-year cumulative incidence of major osteoporotic fracture was 7.1% in those with no auto-PVFx and low auto-AAC, 10.1% in those with no auto-PVFx and high auto-AAC, 13.4% in those with auto-PVFx and low auto-AAC, and 18.0% in those with auto-PVFx and high auto-AAC. While physician manual review of images in clinical practice will still be needed to confirm image quality and provide clinical context for interpretation, simultaneous automated ascertainment of auto-PVFx and auto-AAC can aid fracture risk assessment.

Individuals with calcification of their abdominal aorta (AAC) and vertebral fractures seen on lateral spine bone density images (easily obtained as part of a bone density test) are much more likely to have subsequent fractures. Prior studies have not shown if both AAC and prior vertebral fracture both contribute to fracture prediction in routine clinical practice. Additionally, a barrier to using these images to aid fracture risk assessment at the time of bone density testing has been the need for expert readers to be able to accurately detect both AAC and vertebral fractures. We have developed automated computer methods (using artificial intelligence) to accurately detect vertebral fracture (auto-PVFx) and auto-AAC on lateral spine bone density images for 11 013 older individuals having a bone density test in routine clinical practice. Over a 5-year follow-up period, 7.1% of those with no auto-PVFx and low auto-AAC, 10.1% of those with no auto-PVFx and high auto-AAC, 13.4% of those with auto-PVFx and low auto-AAC, and 18.0% of those with auto-PVFx and high auto-AAC had a major osteoporotic fracture. Auto-PVFx and auto-AAC, ascertained simultaneously on lateral spine bone density images, both contribute to the risk of subsequent major osteoporotic fractures in routine clinical practice settings.

Toxicological safety assessment of HempChoice® hemp oil extract; a proprietary extract consisting of a high concentration of cannabidiol (CBD) in addition to other phytocannabinoids and terpenes derived from CannabissativaL.

HempChoice® Hemp Oil Extract (Geocann, LLC) is an extract of the aerial parts of hemp (Cannabis sativa L.) primarily comprised of 55-75% cannabidiol (CBD), 1-15% other phytocannabinoids and 1-15% terpenes. The results of multiple safety studies demonstrated that it was non-mutagenic in an Ames and mammalian cell micronucleus. test and was well tolerated in a 14-day range-finding study at dose levels up to 96.03. mg/kg BW/day. In the 90-day study, no HempChoice® Hemp Oil Extract-related significant changes were noted in weekly BW, daily BW gain, food consumption, functional observational battery or motor activity assessment. In addition, no HempChoice® Hemp Oil Extract related mortalities, abnormal clinical observations and ophthalmological changes were reported. Some HempChoice® Hemp Oil Extract-related changes were reported in the hematology and clinical chemistry parameters evaluated. These changes were not outside the normal range and were considered reversible during the 28-day recovery period. No macroscopic findings were reported, and histopathological changes related to HempChoice® Hemp Oil Extract exposure were limited to adaptive changes in the liver which were not observed in the recovery group animals. The no observed adverse effect level (NOAEL) for HempChoice® Hemp Oil Extract was determined to be 185.90 mg/kg BW/day in male and female Sprague-Dawley rats.

Quantifying the cost savings of global solar photovoltaic supply chains.

Achieving carbon neutrality requires deploying renewable energy at unprecedented speed and scale1,2, yet countries sometimes implement policies that increase costs by restricting the free flow of capital, talent and innovation in favour of localizing benefits such as economic growth, employment and trade surpluses3,4. Here we assess the cost savings from a globalized solar photovoltaic (PV) module supply chain. We develop a two-factor learning model using historical capacity, component and input material price data of solar PV deployment in the United States, Germany and China. We estimate that the globalized PV module market has saved PV installers US$24 (19-31) billion in the United States, US$7 (5-9) billion in Germany and US$36 (26-45) billion in China from 2008 to 2020 compared with a counterfactual scenario in which domestic manufacturers supply an increasing proportion of installed capacities over a ten-year period. Projecting the same scenario forwards from 2020 results in estimated solar module prices that are approximately 20-25 per cent higher in 2030 compared with a future with globalized supply chains. International climate policy benefits from a globalized low-carbon value chain4, and these results point to the need for complementary policies to mitigate welfare distribution effects and potential impacts on technological crowding out.

Development of a manufacturer-independent convolutional neural network for the automated identification of vertebral compression fractures in vertebral fracture assessment images using active learning.

BACKGROUND: Convolutional neural networks (CNNs) can identify vertebral compression fractures in GE vertebral fracture assessment (VFA) images with high balanced accuracy, but performance against Hologic VFAs is unknown. To obtain good classification performance, supervised machine learning requires balanced and labeled training data. Active learning is an iterative data annotation process with the ability to reduce the cost of labeling medical image data and reduce class imbalance. PURPOSE: To train CNNs to identify vertebral fractures in Hologic VFAs using an active learning approach, and evaluate the ability of CNNs to generalize to both Hologic and GE VFA images. METHODS: VFAs were obtained from the OsteoLaus Study (labeled Hologic Discovery A, n = 2726), the Manitoba Bone Mineral Density Program (labeled GE Prodigy and iDXA, n = 12,742), and the Canadian Longitudinal Study on Aging (CLSA, unlabeled Hologic Discovery A, n = 17,190). Unlabeled CLSA VFAs were split into five equal-sized partitions (n = 3438) and reviewed sequentially using active learning. Based on predicted fracture probability, 17.6% (n = 3032) of the unlabeled VFAs were selected for expert review using the modified algorithm-based qualitative (mABQ) method. CNNs were simultaneously trained on Hologic, GE dual-energy and GE single-energy VFAs. Two ensemble CNNs were constructed using the maximum and mean predicted probability from six separately trained CNNs that differed due to stochastic variation. CNNs were evaluated against the OsteoLaus validation set (n = 408) during the active learning process; ensemble performance was measured against the OsteoLaus test set (n = 819). RESULTS: The baseline CNN, prior to active learning, achieved 55.0% sensitivity, 97.9% specificity, 57.9% positive predictive value (PPV), F1-score 56.4%. Through active learning, 2942 CLSA Hologic VFAs (492 fractures) were added to the training data-increasing the proportion of Hologic VFAs with fractures from 4.2% to 12.5%. With active learning, CNN performance improved to 80.0% sensitivity, 99.7% specificity, 94.1% PPV, F1-score 86.5%. The CNN maximum ensemble achieved 91.9% sensitivity (100% for grade 3 and 95.5% for grade 2 fractures), 99.0% specificity, 81.0% PPV, F1-score 86.1%. CONCLUSION: Simultaneously training on a composite dataset consisting of both Hologic and GE VFAs allowed for the development of a single manufacturer-independent CNN that generalized to both scanner types with good classification performance. Active learning can reduce class imbalance and produce an effective medical image classifier while only labeling a subset of available unlabeled image data-thereby reducing the time and cost required to train a machine learning model.

Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications.

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3-2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days-19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.

How Genomics Is Personalizing the Management of Dyslipidemia and Cardiovascular Disease Prevention.

PURPOSE OF THE REVIEW: To summarize advances in genomic medicine and anticipated future directions to improve cardiovascular risk reduction. RECENT FINDINGS: Mendelian randomization and genome-wide association studies have given significant insights into the role of genetics in dyslipidemia and cardiovascular disease (CVD), with over 160 gene loci found to be associated with coronary artery disease to date. This has enabled the creation of genetic risk scores that have demonstrated improved risk prediction when added to clinical markers of CVD risk. Incorporation of genomic data into clinical patient care is on the horizon. Genomic medicine is expected to offer improved risk assessment, determination of targeted treatment strategies, and improved detection of lipid disorders causal to CVD development.

Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes.

Chronic metabolic diseases have been linked to molecular signatures of mitochondrial dysfunction. Nonetheless, molecular remodeling of the transcriptome, proteome, and/or metabolome does not necessarily translate to functional consequences that confer physiologic phenotypes. The work here aims to bridge the gap between molecular and functional phenomics by developing and validating a multiplexed assay platform for comprehensive assessment of mitochondrial energy transduction. The diagnostic power of the platform stems from a modified version of the creatine kinase energetic clamp technique, performed in parallel with multiplexed analyses of dehydrogenase activities and ATP synthesis rates. Together, these assays provide diagnostic coverage of the mitochondrial network at a level approaching that gained by molecular "-omics" technologies. Application of the platform to a comparison of skeletal muscle versus heart mitochondria reveals mechanistic insights into tissue-specific distinctions in energy transfer efficiency. This platform opens exciting opportunities to unravel the connection between mitochondrial bioenergetics and human disease.

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by a deficiency of lipoprotein lipase leading to extreme hypertriglyceridemia. Patients' burden of illness and quality of life have been poorly addressed in the literature. OBJECTIVE: To understand the ways in which FCS impacts patients' lives. METHODS: Investigation of Findings and Observations Captured in Burden of Illness Survey (IN-FOCUS) was a global web-based survey open to patients with FCS. Survey questions captured information on diagnostic experience, symptoms, comorbidities, disease management, and impact on multiple life dimensions. RESULTS: Of 166 patients in 10 countries, 62% were from the United States and 70% were male. Median age at the time of the survey was 33 years, and median age at diagnosis was 9 years. Patients saw a mean of 5 physicians from different specialties before their FCS diagnosis and experienced multiple physical, emotional, and cognitive symptoms on a daily to monthly basis; 40% were admitted to the hospital in the past year. A lifetime mean of 13 episodes occurred in the 40% of patients with FCS-related acute pancreatitis. Most patients (>90%) found managing fat intake to be difficult, and 53% experienced symptoms despite adherence to their diets. FCS impacted employment status (94%), emotional/mental well-being (58%-66%), and social relationships (68%-82%). CONCLUSIONS: Patients with FCS experience significant clinical and psychosocial burdens that reduce their quality of life and limit employment and social interactions. Increased awareness among healthcare professionals of the multifaceted nature of the FCS disease burden may help expedite diagnosis and timely institution of treatment and broaden management considerations.

Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy volunteers.

BACKGROUND: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. OM3-CA is often prescribed concomitantly with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). OBJECTIVE: The aim of the article was to assess the potential for pharmacokinetic interaction between OM3-CA and the statins rosuvastatin and simvastatin. METHODS: Data from 2 phase I studies (ECLIPSE III and OM-EPA-007 [NCT01486433]) were analyzed. In ECLIPSE III, 59 participants received OM3-CA 4 g once daily for 13 days, with rosuvastatin 40 mg (single dose) co-administered with the 11th dose. In OM-EPA-007, 52 participants received simvastatin 40 mg plus acetylsalicylic acid 81 mg daily for 14 days, with or without OM3-CA. Lack of a drug-drug interaction was declared if the 90% confidence interval (CI) of the geometric least-squares mean ratio of pharmacokinetic parameters was in the range 80% to 125%. RESULTS: For rosuvastatin, values for the geometric mean ratio (90% CI) with:without OM3-CA were 86.38% (80.68-92.48), 90.50% (85.99-95.25), and 89.01% (84.30-93.98), respectively, for maximum plasma concentration (Cmax), area under the concentration-time curve up to last measurable concentration (AUC0-t) and extrapolated to infinity (AUC0-inf). Co-administration with a single dose of rosuvastatin did not affect the multiple-dose pharmacokinetics of constituent OM3-CA fatty acids eicosapentaenoic acid and docosahexaenoic acid. For simvastatin, values for steady state geometric mean ratio (90% CI) with:without OM3-CA were 91.61% (82.82-101.33) and 87.47% (80.19-95.41), respectively, for Cmax and AUC0-t. No deaths or serious adverse events occurred in either trial. CONCLUSION: OM3-CA can be administered with either rosuvastatin or simvastatin without affecting the pharmacokinetics of these statins.

The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study.

BACKGROUND: Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder that is caused by a decrease or an absence of lipoprotein lipase activity. FCS is characterized by marked accumulation of chylomicrons and extreme hypertriglyceridemia, which have major effects on both physical and mental health. To date, there have been no systematic efforts to characterize the impact of chylomicronemia on FCS patients' lives. In particular, the impact of FCS on the burden of illness (BoI) and quality of life (QoL) has not been fully described in the literature. METHODS: IN-FOCUS was a comprehensive web-based research survey of patients with FCS focused on capturing the BoI and impact on QoL associated with FCS. Sixty patients from the US diagnosed with FCS participated. Patients described multiple symptoms spanning across physical, emotional and cognitive domains. RESULTS: Patients on average cycled through 5 physicians of varying specialty before being diagnosed with FCS, reflecting a lengthy journey to diagnosis Nearly all respondents indicated that FCS had a major impact on BoI and QoL and significantly influenced their career choice and employment status, and caused significant work loss due to their disease. CONCLUSION: FCS imparts a considerable burden across multiple domains with reported impairment on activities of daily living and QoL.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE - EXECUTIVE SUMMARYComplete Appendix to Guidelines available at http://journals.aace.com.

OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Each Recommendation is based on a diligent review of the clinical evidence with transparent incorporation of subjective factors. RESULTS: The Executive Summary of this document contains 87 Recommendations of which 45 are Grade A (51.7%), 18 are Grade B (20.7%), 15 are Grade C (17.2%), and 9 (10.3%) are Grade D. These detailed, evidence-based recommendations allow for nuance-based clinical decision making that addresses multiple aspects of real-world medical care. The evidence base presented in the subsequent Appendix provides relevant supporting information for Executive Summary Recommendations. This update contains 695 citations of which 202 (29.1 %) are evidence level (EL) 1 (strong), 137 (19.7%) are EL 2 (intermediate), 119 (17.1%) are EL 3 (weak), and 237 (34.1%) are EL 4 (no clinical evidence). CONCLUSION: This CPG is a practical tool that endocrinologists, other healthcare professionals, regulatory bodies and health-related organizations can use to reduce the risks and consequences of dyslipidemia. It provides guidance on screening, risk assessment, and treatment recommendations for a range of patients with various lipid disorders. These recommendations emphasize the importance of treating low-density lipoprotein cholesterol (LDL-C) in some individuals to lower goals than previously recommended and support the measurement of coronary artery calcium scores and inflammatory markers to help stratify risk. Special consideration is given to patients with diabetes, familial hypercholesterolemia, women, and pediatric patients with dyslipidemia. Both clinical and cost-effectiveness data are provided to support treatment decisions. ABBREVIATIONS: A1C = hemoglobin A1C ACE = American College of Endocrinology ACS = acute coronary syndrome AHA = American Heart Association ASCVD = atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo = apolipoprotein BEL = best evidence level CKD = chronic kidney disease CPG = clinical practice guidelines CVA = cerebrovascular accident EL = evidence level FH = familial hypercholesterolemia HDL-C = high-density lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HIV = human immunodeficiency virus HoFH = homozygous familial hypercholesterolemia hsCRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol Lp-PLA2 = lipoprotein-associated phospholipase A2 MESA = Multi-Ethnic Study of Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction NCEP = National Cholesterol Education Program PCOS = polycystic ovary syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerides VLDL-C = very low-density lipoprotein cholesterol.

Development and Content Validity of the Statin Experience Assessment Questionnaire (SEAQ)©.

INTRODUCTION: The National Lipid Association Statin Intolerance (SI) Panel recognized the need for better understanding of the patient SI experience. OBJECTIVE: The objective of this research was to develop a patient-reported outcome (PRO) questionnaire to assess a patient's experience with SI. METHODS: Questionnaire development was informed via a series of research activities: literature review, concept elicitation, item generation, and content evaluation. Following the literature review and concept elicitation, a draft questionnaire was constructed and subsequently modified based on feedback from therapeutic area experts and patients via cognitive debriefing interviews. RESULTS: Muscle-related symptoms were the most commonly reported symptoms associated with SI in the literature review (35 of 41 articles reviewed [85%]) and in semi-structured interviews with experts (n = 5 [100%]) and patients (n = 17 of 20 [85.0%]). Physical and other impacts of SI symptoms on daily activities were also frequently reported. A 17-item draft questionnaire was created, and cognitive debriefing with experts (n = 5) and patients (n = 15) was conducted. Overall, the items, response options, and instructions were comprehensible and positively reviewed; minor changes resulted in the 15-item Statin Experience Assessment Questionnaire (SEAQ)©. Using a 30-day recall period, the SEAQ© assesses the severity and impact of six SI symptoms (muscle ache, muscle pain, muscle cramps, muscle weakness, tiredness, and joint pain) on an 11-point numeric scale. Statin discontinuation and likelihood of discontinuation due to symptoms are assessed and scored on a yes/no and five-point verbal response scale, respectively. CONCLUSION: The SEAQ

The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of High-Intensity Statin Therapy: Does Statin Type Matter?

The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management have placed greater emphasis on high-intensity statin dosing for those with known cardiovascular disease or diabetes mellitus. Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis specifically between the high-intensity statins and the most common moderate-intensity statin, simvastatin, were not found to a significant degree in this review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear to be more important regarding the risk of these adverse effects. Pharmacogenetic differences in statin metabolism may explain individual susceptibility, however genetic testing is not felt to be cost effective at this time. More importantly, statin choice should consider concomitant use of the many prevalent CYP3A4 inhibitors or inducers, and when present, rosuvastatin selection is recommended to reduce DDIs and risk of statin-induced adverse effects.

Quantitative assessment of fluorescent proteins.

The advent of fluorescent proteins (FPs) for genetic labeling of molecules and cells has revolutionized fluorescence microscopy. Genetic manipulations have created a vast array of bright and stable FPs spanning blue to red spectral regions. Common to autofluorescent FPs is their tight ß-barrel structure, which provides the rigidity and chemical environment needed for effectual fluorescence. Despite the common structure, each FP has unique properties. Thus, there is no single 'best' FP for every circumstance, and each FP has advantages and disadvantages. To guide decisions about which FP is right for a given application, we have quantitatively characterized the brightness, photostability, pH stability and monomeric properties of more than 40 FPs to enable straightforward and direct comparison between them. We focus on popular and/or top-performing FPs in each spectral region.

A Nation-Wide Study on the Percentage of Schizophrenia and Bipolar Disorder Patients Who Earn Minimum Wage or Above.

OBJECTIVE: Although it is undisputable that patients with severe mental illness have impaired ability to work, the extent of this is unclear. This is a nation-wide, cross-sectional survey of patients who have been hospitalized with severe mental illness earning minimum wage or above. METHOD: Data from the Israeli Psychiatric Hospitalization Case Registry were linked with nation-wide data from the National Insurance Institute (the equivalent of US Social Security) on personal income. Hospitalization data were obtained on all consecutive admissions to any psychiatric hospital in the country between 1990-2008 with a diagnosis of schizophrenia, other nonaffective psychotic disorders, or bipolar disorder (N = 35 673). Earning minimum wage or more was defined as earning at least 1000 USD/month, which was equivalent to minimum wage in Israel in December 2010. RESULTS: The percentages of patients with only 1 admission who were earning minimum wage or above in December 2010 were as follows: 10.6% of patients with a diagnosis of schizophrenia; 21.6% of patients with a diagnosis of nonaffective psychotic disorders; and 24.2% of patients with bipolar disorder. The percentages of patients with multiple admissions who were earning minimum wage or above were as follows: 5.8% of patients with schizophrenia; 11.2% of patients with nonaffective psychotic disorders; and 19.9% of patients with bipolar disorder. CONCLUSIONS: Despite potential confounders, the results indicate that patients with schizophrenia, nonaffective psychotic disorders, or bipolar disorder have a poor employment outcome, even if they have only been admitted once. These results emphasize the importance of improving interventions to re-integrate these individuals into the work force.

Report on ISCTM Consensus Meeting on Clinical Assessment of Response to Treatment of Cognitive Impairment in Schizophrenia.

If treatments for cognitive impairment are to be utilized successfully, clinicians must be able to determine whether they are effective and which patients should receive them. In order to develop consensus on these issues, the International Society for CNS Clinical Trials and Methodology (ISCTM) held a meeting of experts on March 20, 2014, in Washington, DC. Consensus was reached on several important issues. Cognitive impairment and functional disability were viewed as equally important treatment targets. The group supported the notion that sufficient data are not available to exclude patients from available treatments on the basis of age, severity of cognitive impairment, severity of positive symptoms, or the potential to benefit functionally from treatment. The group reached consensus that cognitive remediation is likely to provide substantial benefits in combination with procognitive medications, although a substantial minority believed that medications can be administered without nonpharmacological therapy. There was little consensus on the best methods for assessing cognitive change in clinical practice. Some participants supported the view that performance-based measures are essential for measurement of cognitive change; others pointed to their cost and time requirements as evidence of impracticality. Interview-based measures of cognitive and functional change were viewed as more practical, but lacking validity without informant involvement or frequent contact from clinicians. The lack of consensus on assessment methods was viewed as attributable to differences in experience and education among key stakeholders and significant gaps in available empirical data. Research on the reliability, validity, sensitivity, and practicality of competing methods will facilitate consensus.

The cost of ipilimumab toxicity: a single-centre analysis.

There are no published data on the costs associated with investigating and managing toxicity from ipilimumab treatment in patients with metastatic melanoma. Patients treated with ipilimumab at The Royal Marsden Hospital between 1 September 2010 and 1 April 2013 were identified. Data on demographics, investigations and survival outcomes were collected. Patients with grade 3 or higher immune-related adverse events were identified, and costs of investigating and managing toxicities in them were calculated on the basis of standard National Health Service tariffs. Out of the 110 patients, 29 experienced grade 3/4 immune-related adverse events. The total cost of investigating and managing these patients was £140,680, or a median cost of £2860 per patient. Patients experiencing grade 3/4 toxicities had 1-, 2- and 3-year survival rates of 79, 59 and 46%, compared with 24, 17 and 15% in the group that did not experience significant toxicity (P<0.0005). The most common treatment-related toxicity identified was colitis. Two patients died from complications associated with ipilimumab colitis. The cost of ipilimumab toxicity is marginal in comparison with the total treatment cost. Patients treated with ipilimumab who develop significant toxicity have a higher than expected 1-, 2- and 3-year survival.