Online biology degree program broadens access for women, first-generation to college, and low-income students, but grade disparities remain.
Online education has grown rapidly in recent years with many universities now offering fully online degree programs even in STEM disciplines. These programs have the potential to broaden access to STEM degrees for people with social identities currently underrepresented in STEM. Here, we ask to what extent is that potential realized in terms of student enrollment and grades for a fully online degree program. Our analysis of data from more than 10,000 course-enrollments compares student demographics and course grades in a fully online biology degree program to demographics and grades in an equivalent in-person biology degree program at the same university. We find that women, first-generation to college students and students eligible for federal Pell grants constitute a larger proportion of students in the online program compared to the in-person mode. However, the online mode of instruction is associated with lower course grades relative to the in-person mode. Moreover, African American/Black, Hispanic/Latinx, Native American, and Pacific Islander students as well as federal Pell grant eligible students earned lower grades than white students and non-Pell grant eligible students, respectively, but the grade disparities were similar among both in-person and online student groups. Finally, we find that grade disparities between men and women are larger online compared to in-person, but that for first-generation to college women, the online mode of instruction is associated with little to no grade gap compared to continuing generation women. Our findings indicate that although this online degree program broadens access for some student populations, inequities in the experience remain and need to be addressed in order for online education to achieve its inclusive mission.


Bio-Integrated Wearable Systems: A Comprehensive Review.
Bio-integrated wearable systems can measure a broad range of biophysical, biochemical, and environmental signals to provide critical insights into overall health status and to quantify human performance. Recent advances in material science, chemical analysis techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technology, characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of "bio-integrated" technologies in a comprehensive manner that connects fundamental developments in chemistry, material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and associated platforms that appear in following sections. The subsequent content highlights the most advanced biosensors, classified according to their ability to capture biophysical, biochemical, and environmental information. Additional sections feature schemes for electrically powering these sensors and strategies for achieving fully integrated, wireless systems. The review concludes with an overview of key remaining challenges and a summary of opportunities where advances in materials chemistry will be critically important for continued progress.


Risk factors for stuttering: a secondary analysis of a large data base.
The spectrum of risk and concomitant factors in stuttering is generally thought to be wide and heterogeneous. However, only a few studies have examined these factors using information from large databases. We examined the data on 11,905 Swiss conscripts from 2003. All cases with high psychiatric screening scores indicating "caseness" for a psychiatric disorder were excluded, among them potential malingerers, so that 9,814 records remained. The analyses rely on self-reported information about stuttering in childhood, problems at birth, problems in school, mental disorders of parents and relatives, childhood adversity and socio-demographic information. Statistical modelling was done using logistic regression and path analysis models. Risk factors determined in the logistic regression include premature birth, probable attention deficit hyperactive disorder, alcohol abuse of the parents, obsessive-compulsive disorder in parents and relatives, having a disabled mother and having a parent from a foreign country. There is no overwhelmingly strong risk factor; all odds ratios are about 2 or below. In conclusion, large databases are helpful in revealing less obvious and less frequent risk factors for heterogeneous disorders such as stuttering. Obviously, not only secondary analyses, but also systematical large scale studies would be required to complete the complex epidemiological puzzle in stuttering. An extensive examination of young adults who were initially assessed in childhood might provide the most promising design.


Eicosapentaenoic and Arachidonic Acids from Phytophthora infestans Elicit Fungitoxic Sesquiterpenes in the Potato.
Mycelial extracts from Phytophthora infestans caused necrosis and elicited the accumulation of antimicrobial stress metabolites in potato tubers. A portion of the material with elicitor activity could be extracted from the mycelium by a mixture of chloroform and methanol. The most active elicitors of stress metabolites in these extracts were eicosapentaenoic and arachidonic acids. These fatty acids were found in either free or esterified form in all active fractions of the mycelial extracts.


EEG anomalies in adult ADHD subjects performing a working memory task.
Functional imaging studies have revealed differential brain activation patterns in attention deficit hyperactivity disorder (ADHD) adult patients performing working memory (WM) tasks. The existence of alterations in WM-related cortical circuits during childhood may precede executive dysfunctions in this disorder in adults. To date, there is no study exploring the electrophysiological activation of WM-related neural networks in ADHD. To address this issue, we carried out an electroencephalographic (EEG) activation study associated with time-frequency (TF) analysis in 15 adults with ADHD and 15 controls performing two visual N-back WM tasks, as well as oddball detection and passive fixation tasks. Frontal transient (phasic) theta event-related synchronization (ERS, 0-500 msec) was significantly reduced in ADHD as compared to control subjects. Such reduction was equally present in a task-independent manner. In contrast, the power of the later sustained (∼500-1200 msec) theta ERS for all tasks was comparable in ADHD and control groups. In active WM tasks, ADHD patients displayed lower alpha event-related desynchronization (ERD, ∼200-900 msec) and higher subsequent alpha ERS (∼900-2400 msec) compared to controls. The time course of alpha ERD/ERS cycle was modified in ADHD patients compared to controls, suggesting that they are able to use late compensatory mechanisms in order to perform this WM task. These findings support the idea of an ADHD-related dysfunction of neural generators sub-serving attention directed to the incoming visual information. ADHD cases may successfully face WM needs depending on the preservation of sustained theta ERS and prolonged increase of alpha ERS at later post-stimulus time points.


How do we safely treat depression in children, adolescents and young adults?
Increasing concerns about the safety and efficacy of antidepressant drugs for children, adolescents and young adults have been countered by claims that reduced prescribing of antidepressants may have dangerous consequences. This leaves clinicians unsure as to how to weigh up the evidence and apply it to their patients. This paper promotes an approach of evaluating the evidence in each study according to the importance of the outcomes being measured in that study. It finds that on important measures such as mortality, hospitalization and quality of life, the evidence is unfavourable for antidepressants in this population. Here, an approach is suggested that primary care physicians might adopt with their depressed young patients. Through a combination of 'watchful waiting' and physical and emotional rehabilitation, physicians can actively intervene without reliance on medication or psychotherapy.


Measuring vision using innate behaviours in mice with intact and impaired retina function.
Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that don't require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.


Management of urolithiasis in patients with chronic kidney disease.
Management of urolithiasis in patients with chronic kidney disease. To ascertain the best method surgical or noninvasive. This was a single-institute study. A total of 50 patients of CKD with urolithiasis were enrolled in this comparative study. Clinical evaluation, biochemical evaluation, and radiological imaging were done. The management strategies were individualized to patient need. Following procedure, imaging and biochemical assessment were done to assess the stone clearance and improvement in the renal parameters. Intraoperative and postoperative complications are also noted. The patients were followed up to 6 months. Statistical Package for the Social Sciences version 21.0 software was used for statistical analysis. The mean age of the patients was 55.22 ± 10.76 years (range 28-76). Majority were male (76%) and had unilateral involvement. The mean preoperative hemoglobin (Hb), urea, creatinine, and total leukocyte count (TLC) were 9.49 ± 0.84 g%, 71.13 ± 24.09 mg/dl, 4.71 ± 2.45 mg/dl, and 8.67 ± 1.81 thousands/cumm, respectively. Percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URSL) were the most common procedures performed in 23 (46%) and 12 (24%) patients, respectively. In 5 (10%) patients, PCNL with URSL was used. The clearance rate for different techniques ranged from 40% (PCNL with URSL) to 91.7% (URSL alone). The overall clearance rate was 78.3%. Fever (40%) and deranged renal function test requiring hemodialysis (16%) were the most common postoperative complications. Postoperatively, a significant decline in the mean Hb, serum (S.) urea, and S. creatinine was observed. The mean TLC levels showed a significant increase. During follow-up, S. creatinine levels showed consistent decline. Auxiliary procedures were needed in six (12%) cases. There were two (4%) mortalities. The management of urolithiasis among CKD patients requires individualized approaches. The selection of appropriate strategy results in good outcome and minimum complications.


Increased resting state connectivity between ipsilesional motor cortex and contralesional premotor cortex after transcranial direct current stimulation with physical therapy.
Non-invasive stimulation of the brain using transcranial direct current stimulation (tDCS) during motor rehabilitation can improve the recovery of movements in individuals with stroke. However, the neural substrates that underlie the clinical improvements are not well understood. In this proof-of-principle open-label pilot study, five individuals with stroke received 10 sessions of tDCS while undergoing usual care physical/occupational therapy for the arm and hand. Motor impairment as indexed by the Upper Extremity Fugl Meyer assessment was significantly reduced after the intervention. Resting state fMRI connectivity increased between ipsilesional motor cortex and contralesional premotor cortex after the intervention. These findings provide preliminary evidence that the neural underpinnings of tDCS coupled with rehabilitation exercises, may be mediated by interactions between motor and premotor cortex. The latter, of which has been shown to play an important role in the recovery of movements post-stroke. Our data suggest premotor cortex could be tested as a target region for non-invasive brain-stimulation to enhance connectivity between regions that might be beneficial for stroke motor recovery.


StO₂ guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial.
The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO₂) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO₂. StO₂ was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO₂ above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO₂ over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO₂ as a treatment goal. However, the protocol showed no clear trend for or against targeting StO₂.


How to improve outbreak response: a case study of integrated outbreak analytics from Ebola in Eastern Democratic Republic of the Congo.
The emerging field of outbreak analytics calls attention to the need for data from multiple sources to inform evidence-based decision making in managing infectious diseases outbreaks. To date, these approaches have not systematically integrated evidence from social and behavioural sciences. During the 2018-2020 Ebola outbreak in Eastern Democratic Republic of the Congo, an innovative solution to systematic and timely generation of integrated and actionable social science evidence emerged in the form of the Cellulle d'Analyse en Sciences Sociales (Social Sciences Analytics Cell) (CASS), a social science analytical cell. CASS worked closely with data scientists and epidemiologists operating under the Epidemiological Cell to produce integrated outbreak analytics (IOA), where quantitative epidemiological analyses were complemented by behavioural field studies and social science analyses to help better explain and understand drivers and barriers to outbreak dynamics. The primary activity of the CASS was to conduct operational social science analyses that were useful to decision makers. This included ensuring that research questions were relevant, driven by epidemiological data from the field, that research could be conducted rapidly (ie, often within days), that findings were regularly and systematically presented to partners and that recommendations were co-developed with response actors. The implementation of the recommendations based on CASS analytics was also monitored over time, to measure their impact on response operations. This practice paper presents the CASS logic model, developed through a field-based externally led consultation, and documents key factors contributing to the usefulness and adaption of CASS and IOA to guide replication for future outbreaks.


RNA polymerase II-TFIIB structure and mechanism of transcription initiation.
To initiate gene transcription, RNA polymerase II (Pol II) requires the transcription factor IIB (B). Here we present the crystal structure of the complete Pol II-B complex at 4.3 A resolution, and complementary functional data. The results indicate the mechanism of transcription initiation, including the transition to RNA elongation. Promoter DNA is positioned over the Pol II active centre cleft with the 'B-core' domain that binds the wall at the end of the cleft. DNA is then opened with the help of the 'B-linker' that binds the Pol II rudder and clamp coiled-coil at the edge of the cleft. The DNA template strand slips into the cleft and is scanned for the transcription start site with the help of the 'B-reader' that approaches the active site. Synthesis of the RNA chain and rewinding of upstream DNA displace the B-reader and B-linker, respectively, to trigger B release and elongation complex formation.


Dissociable prefrontal brain systems for attention and emotion.
The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders.


Cognitive impairment and associated loss in brain white microstructure in aircrew members exposed to engine oil fumes.
Cabin air in airplanes can be contaminated with engine oil contaminants. These contaminations may contain organophosphates (OPs) which are known neurotoxins to brain white matter. However, it is currently unknown if brain white matter in aircrew is affected. We investigated whether we could objectify cognitive complaints in aircrew and whether we could find a neurobiological substrate for their complaints. After medical ethical approval from the local institutional review board, informed consent was obtained from 12 aircrew (2 females, on average aged 44.4 years, 8,130 flying hours) with cognitive complaints and 11 well matched control subjects (2 females, 43.4 years, 233 flying hours). Depressive symptoms and self-reported cognitive symptoms were assessed, in addition to a neuropsychological test battery. State of the art Magnetic Resonance Imaging (MRI) techniques were administered that assess structural and functional changes, with a focus on white matter integrity. In aircrew we found significantly more self-reported cognitive complaints and depressive symptoms, and a higher number of tests scored in the impaired range compared to the control group. We observed small clusters in the brain in which white matter microstructure was affected. Also, we observed higher cerebral perfusion values in the left occipital cortex, and reduced brain activation on a functional MRI executive function task. The extent of cognitive impairment was strongly associated with white matter integrity, but extent of estimated number of flight hours was not associated with cognitive impairment nor with reductions in white matter microstructure. Defects in brain white matter microstructure and cerebral perfusion are potential neurobiological substrates for cognitive impairments and mood deficits reported in aircrew.


A virtual instrument to standardise the calibration of atomic force microscope cantilevers.
Atomic force microscope (AFM) users often calibrate the spring constants of cantilevers using functionality built into individual instruments. This calibration is performed without reference to a global standard, hindering the robust comparison of force measurements reported by different laboratories. Here, we describe a virtual instrument (an internet-based initiative) whereby users from all laboratories can instantly and quantitatively compare their calibration measurements to those of others-standardising AFM force measurements-and simultaneously enabling non-invasive calibration of AFM cantilevers of any geometry. This global calibration initiative requires no additional instrumentation or data processing on the part of the user. It utilises a single website where users upload currently available data. A proof-of-principle demonstration of this initiative is presented using measured data from five independent laboratories across three countries, which also allows for an assessment of current calibration.


CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies.
The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin's lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This commentary summarizes the current state of knowledge on CAR T cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.


The Control of Stress Induced Type I Diabetes Mellitus in Humans through the Hepatic Synthesis of Insulin by the Stimulation of Nitric Oxide Production.
The role of stress induced development of Type-1 diabetes mellitus (T1DM) as opposed to autoimmunity remains obscure. It has been reported that a stress induced protein, identified to be dermcidin isoform 2 (dermcidin) inhibited insulin synthesis in both the pancreatic β cells and the hepatic cells. As dermcidin effect could be neutralized by the increased production of systemic nitric oxide (NO), investigations were carried out to determine the feasibility of controlling stress induced T1DM through the neutralization of dermcidin by systemic increase of NO. To determine the role of plasma dermcidin level in T1DM subjects (n=45), if any, when the plasma dermcidin level were determined, it was found that the protein level was increased in 65% of the participating volunteers. Efforts were made to normalize the plasma glucose level (median=175 mg/dL) in these T1DM subjects by systemic increase of NO by applying a cotton pad containing 0.28mmol sodium nitroprusside on the abdominal skin. It was found that the systemic increase of NO level decreased the blood glucose level of 275 mg/dL (median) to 115 mg/dL (median) in these volunteers within 24 h with concomitant increase of plasma insulin level from 7.5 μunits/dL to 101 μunits/dL at the same time. The increase of plasma insulin level was accompanied by the decrease of dermcidin level of 124.5 nM to 18 nM with increase of NO from 0.43 ± 0.19 nM to 4.1 ± 1.56 nM. The results suggested that the stress induced T1DM by dermcidin could be controlled by the systemic increase of NO which in consequence led to increased synthesis of insulin.


Emerging evidence of the role of gut microbiota in the development of allergic diseases.
The purpose is to review recent studies examining the role of gut microbiota in allergic diseases and asthma. Work in experimental models gives further evidence that a disturbed gut microbiota influences the propensity to develop allergic manifestations, and that changing the gut microbiota by dietary means (high fiber/acetate or prebiotics) in pregnancy may reduce the risk of allergic airways disease and food allergy in the offspring, respectively. The gut microbiome in established allergic disease and prior to disease onset has also been assessed in clinical trials. One study demonstrated a strong association between high abundance of Faecalibacterium prausnitzii and decreased levels of butyrate and propionate, and established eczema. Lower relative abundance of Ruminococcaceae appears to be implicated in food sensitization and to precede the development of atopic eczema. Decreased relative abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia in early infancy was reported to be associated with increased asthma risk. Inoculation of germ-free mice with these genera decreased airway inflammation in their offspring thereby proposing a causal role of bacteria in preventing allergic airways disease. Gut microbiome research is an actively developing field. Although candidate bacterial taxa have been reported it still remains unclear which bacteria (or other microbes), in which numbers and combinations, and when during the gut colonization process may prevent allergic diseases and asthma. There is still a call for standardized approaches that will enable direct comparison of different studies.


Iron-induced fluorescence in the retina: dependence on vitamin A.
Intravitreal iron injection induces fluorophore formation in the photoreceptor outer segments, followed by an accumulation of inclusions with lipofuscin-like fluorescence in the retinal pigment epithelium (RPE). The accumulation of RPE lipofuscin during aging is dependent on vitamin A availability. Experiments were conducted to determine whether iron-induced fluorophore formation in the outer segments and in RPE is also dependent on vitamin A, and thus whether oxidation promotes the participation of vitamin A in lipofuscin formation. For 23 weeks, beginning at weaning, albino Fischer rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After 23 weeks, when rhodopsin levels had decreased more than 90% in the -A rats, some animals in this group were given an intramuscular injection of all-trans retinol and were allowed to recover from retinoid deficiency for 7 days (-A+A). Animals in all three treatment groups were then given an intravitreal injection of ferrous sulfate. Both 1 day and 7 days after the iron injections, the retinas and RPEs were examined for fluorophores with excitation and emission properties similar to those of RPE lipofuscin fluorophores. In retina sections examined with fluorescence microscopy 24 hours after the ferrous sulfate treatment, the photoreceptor outer segments of rats in all of the treatment groups displayed a fluorescence with a blue emission maximum. This outer-segment fluorescence was not present in untreated eyes. The in situ outer-segment fluorescence was correlated with the appearance of blue-emitting fluorophores in organic solvent extracts of the retinas. One week after the iron injections, the RPE cells of the +A animals became filled with inclusions that displayed a golden-yellow fluorescence emission when excited by blue light. Very little of this lipofuscin-like fluorescence was observed in the RPE of the -A rats 1 week after iron treatment. However, in the -A rats that had been repleted with vitamin A, the ability of iron to induce the RPE fluorescence was restored. Several orange-emitting fluorophores were present in organic solvent extracts of the RPE-choroids of the +A rats. The amounts of these fluorophores were not appreciably affected by the iron treatment. These orange-emitting compounds were not observed in extracts of any eyes in the -A or -A+A groups. The results of this study suggest that oxidation of the photoreceptor outer-segment lipids generates blue-emitting fluorophores that are not directly involved in RPE lipofuscin fluorophore formation. The findings also indicate that retinoids are direct precursors of RPE lipofuscin fluorophores, and that oxidative stress to the retina promotes participation of vitamin A in the formation of some of the compounds responsible for RPE lipofuscin fluorescence.


Clinical Performance of Aspergillus PCR for Testing Serum and Plasma: a Study by the European Aspergillus PCR Initiative.
Aspergillus PCR testing of serum provides technical simplicity but with potentially reduced sensitivity compared to whole-blood testing. With diseases for which screening to exclude disease represents an optimal strategy, sensitivity is paramount. The associated analytical study confirmed that DNA concentrations were greater in plasma than those in serum. The aim of the current investigation was to confirm analytical findings by comparing the performance of Aspergillus PCR testing of plasma and serum in the clinical setting. Standardized Aspergillus PCR was performed on plasma and serum samples concurrently obtained from hematology patients in a multicenter retrospective anonymous case-control study, with cases diagnosed according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (19 proven/probable cases and 42 controls). Clinical performance and clinical utility (time to positivity) were calculated for both kinds of samples. The sensitivity and specificity for Aspergillus PCR when testing serum were 68.4% and 76.2%, respectively, and for plasma, they were 94.7% and 83.3%, respectively. Eighty-five percent of serum and plasma PCR results were concordant. On average, plasma PCR was positive 16.8 days before diagnosis and was the earliest indicator of infection in 13 cases, combined with other biomarkers in five cases. On average, serum PCR was positive 10.8 days before diagnosis and was the earliest indicator of infection in six cases, combined with other biomarkers in three cases. These results confirm the analytical finding that the sensitivity of Aspergillus PCR using plasma is superior to that using serum. PCR positivity occurs earlier when testing plasma and provides sufficient sensitivity for the screening of invasive aspergillosis while maintaining methodological simplicity.


Cue utilization and encoding specificity in picture recognition by older adults.
According to the encoding specificity principle, memory is best when encoding and retrieval conditions are compatible. Some researchers have suggested that older adults encode information in a general fashion and are less sensitive to the specific contextual aspects of a memory situation due to limited processing resources. We investigated the hypothesis that age interacts with encoding specificity. Young and old adults studied target pictures in the presence or absence of pictorial cues factorially varied at encoding and retrieval. If the older adults used the specific cuing information differently from the younger adults, age should have interacted with the encoding and retrieval variables. The results provided no evidence for such an interaction and indicated that both ages showed evidence of encoding specificity. To investigate the role of processing resources in encoding specificity, old and young adults also studied the pictures while simultaneously performing a digit-monitoring task. The divided-attention manipulation also did not interact with age, as both young and old adults showed encoding specificity effects of comparable magnitude in both control and divided-attention conditions.


Prediction of Mortality After ALPPS Stage-1: An Analysis of 320 Patients From the International ALPPS Registry.
The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2. ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown. Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality. Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive. This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.


Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina.
We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies.


Non-Hodgkin's lymphomas and occupation in Sweden.
To investigate whether there is a risk excess of non-Hodgkin's lymphoma among Swedish workers associated with particular occupations. The base population was made up of Swedish men (1,779,646) and women (1,101,669) who were gainfully employed at the time of the 1970 census, had also been present in the 1960 census and were still alive and older than 24 years as of 1 January, 1971. They were followed up for 19 years until the end of 1989. Age-period standardised incidence ratios were computed in a dataset linking cancer diagnoses from the Swedish national cancer register to occupational and demographic data obtained in the census of 1970. Log-linear Poisson models were fitted, allowing for geographical area. Risk estimators per occupation were also computed for workers reporting the same occupation in 1960 and 1970, a more specifically exposed group. There were 7,610 non-Hodgkin's lymphomas reported in the study cohort, 5,391 cases in men and 2,219 in women. A relative risk of over 1.20 and statistically significant was observed in men among accountants and auditors, secretaries and typists, auctionists, non-specified rail and road transport workers, telecommunications traffic officers, telegraph and radio operators, photographic-laboratory workers and other production and related work. The risk excess was confirmed in men with the same occupation in both censuses. In women, only three occupations achieved statistical significance: metal platers and coaters, truck and conveyor operators and store and warehouse workers. The risk excess observed in telecommunication and transport workers could be explained by electromagnetic radiation exposure. We did not find a risk excess in agricultural occupations, that has been largely documented by other study groups.


Outcome measures for pediatric laryngotracheal reconstruction: International consensus statement.
Develop multidisciplinary and international consensus on patient, disease, procedural, and perioperative factors, as well as key outcome measures and complications, to be reported for pediatric airway reconstruction studies. Standard Delphi methods were applied. Participants proposed items in three categories: 1) patient/disease characteristics, 2) procedural/intraoperative/perioperative factors, and 3) outcome measures and complications. Both general and anatomic site-specific measures were elicited. Participants also suggested specific operations to be encompassed by this project. We then used iterative ranking and review to develop consensus lists via a priori Delphi consensus criteria. Thirty-three pediatric airway experts from eight countries in North and South America, Europe, and Australia participated, representing otolaryngology (including International Pediatric Otolaryngology Group members), pulmonology, general surgery, and cardiothoracic surgery. Consensus led to inclusion of 19 operations comprising open expansion, resection, and slide procedures of the larynx, trachea, and bronchi as well as three endoscopic procedures. Consensus was achieved on multiple patient/comorbidity (10), disease/stenosis (7), perioperative-/intraoperative-/procedure-related (16) factors. Consensus was reached on multiple outcome and complication measures, both general and site-specific (8 general, 13 supraglottic, 15 glottic, 17 subglottic, 8 cervical tracheal, 12 thoracic tracheal). The group was able to clarify how each outcome should be measured, with specific instruments defined where applicable. This consensus statement provides a framework to communicate results consistently and reproducibly, facilitating meta-analyses, quality improvement, transfer of information, and surgeon self-assessment. It also clarifies expert opinion on which patient, disease, procedural, and outcome measures may be important to consider in any pediatric airway reconstruction patient. 5 Laryngoscope, 129:244-255, 2019.


Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common therapeutic products used for the management of inflammation and pain. However, their use is associated with gastrointestinal (GI), cardiovascular and renal complications. Although prevalence data regarding NSAID-induced complications are available worldwide, but none of the study has assessed the prevalence of GI, cardiac and renal complications in India. This study aimed to assess the point prevalence of GI, cardiac and renal complications associated with the use of NSAIDs in India. The study also aimed to evaluate the association between the risk factors and GI, renal and cardiac complications in patients using NSAIDs. This prospective, cross-sectional, multi-centric study was conducted in eight medical colleges across India (North, East, West, South and Central India). Data related to GI complications including gastric, duodenal and gastroduodenal erosions/ulcers/gastritis, renal complications including acute and chronic renal failure or cardiac complications including acute coronary syndrome (ACS), acute myocardial infarction (AMI) and cardiac failure, were collected from patients. The cut-off date for interim data analysis was July 7, 2014. A total of 2,140 patients out of 3,600 were enrolled from eight centers at the time of interim analysis. The NSAID-associated point prevalence of GI complications was 30.08%; cardiac complication was 42.77%; and renal complication was 27.88%. Results of the present interim analysis show that the prevalence of GI, cardiac and renal complications among patients is high due to exaggerated usage; however, the final analysis would provide the overall prevalence of these complications.


Innovating within the ACGME regulatory environment is not an oxymoron.
The aim of this study was to describe the analysis of program citations and cycle length for reaccreditation in the 14 family medicine residencies participating in the P4 project. An exploratory narrative analysis was conducted on all actions taken by the Review Committee for Family Medicine (RC-FM) between 2003 and 2012. The analysis included cycle length and types of citations associated with accreditation actions. Several validation steps were undertaken to confirm findings reported. Mean cycle length for all P4 programs was 4.0 before P4 (2007) and did not change significantly during P4. The average number of citations per program before P4 was 6.2, and during P4 the average was 6.8. The P4 averages were similar to national norms during the project period. The citations that most commonly decreased during the P4 project were: Continuity of Patient Care/Inpatient, FMC Patient Population/Patient Volume, Orthopedics or Sports Medicine Curriculum, Resident Final Evaluation, Resident Workload/Duty Hours, and Resident Attrition. The citations that most commonly increased during the P4 project were FMC Patient Population/Demographics, Certifying Exam Scores, and Management of Health Systems Curriculum. Innovation and redesign of residency training in the P4 programs appears not to have affected the average cycle length or number of citations per program. The current regulatory environment in family medicine residency education appears to allow for innovation and experimentation.


ISRIA statement: ten-point guidelines for an effective process of research impact assessment.
As governments, funding agencies and research organisations worldwide seek to maximise both the financial and non-financial returns on investment in research, the way the research process is organised and funded is becoming increasingly under scrutiny. There are growing demands and aspirations to measure research impact (beyond academic publications), to understand how science works, and to optimise its societal and economic impact. In response, a multidisciplinary practice called research impact assessment is rapidly developing. Given that the practice is still in its formative stage, systematised recommendations or accepted standards for practitioners (such as funders and those responsible for managing research projects) across countries or disciplines to guide research impact assessment are not yet available.In this statement, we propose initial guidelines for a rigorous and effective process of research impact assessment applicable to all research disciplines and oriented towards practice. This statement systematises expert knowledge and practitioner experience from designing and delivering the International School on Research Impact Assessment (ISRIA). It brings together insights from over 450 experts and practitioners from 34 countries, who participated in the school during its 5-year run (from 2013 to 2017) and shares a set of core values from the school's learning programme. These insights are distilled into ten-point guidelines, which relate to (1) context, (2) purpose, (3) stakeholders' needs, (4) stakeholder engagement, (5) conceptual frameworks, (6) methods and data sources, (7) indicators and metrics, (8) ethics and conflicts of interest, (9) communication, and (10) community of practice.The guidelines can help practitioners improve and standardise the process of research impact assessment, but they are by no means exhaustive and require evaluation and continuous improvement. The prima facie effectiveness of the guidelines is based on the systematised expert and practitioner knowledge of the school's faculty and participants derived from their practical experience and research evidence. The current knowledge base has gaps in terms of the geographical and scientific discipline as well as stakeholder coverage and representation. The guidelines can be further strengthened through evaluation and continuous improvement by the global research impact assessment community.


Architectural properties of distal forelimb muscles in horses, Equus caballus.
Articular injuries in athletic horses are associated with large forces from ground impact and from muscular contraction. To accurately and noninvasively predict muscle and joint contact forces, a detailed model of musculoskeletal geometry and muscle architecture is required. Moreover, muscle architectural data can increase our understanding of the relationship between muscle structure and function in the equine distal forelimb. Muscle architectural data were collected from seven limbs obtained from five thoroughbred and thoroughbred-cross horses. Muscle belly rest length, tendon rest length, muscle volume, muscle fiber length, and pennation angle were measured for nine distal forelimb muscles. Physiological cross-sectional area (PCSA) was determined from muscle volume and muscle fiber length. The superficial and deep digital flexor muscles displayed markedly different muscle volumes (227 and 656 cm3, respectively), but their PCSAs were very similar due to a significant difference in muscle fiber length (i.e., the superficial digital flexor muscle had very short fibers, while those of the deep digital flexor muscle were relatively long). The ulnaris lateralis and flexor carpi ulnaris muscles had short fibers (17.4 and 18.3 mm, respectively). These actuators were strong (peak isometric force, Fmax=5,814 and 4,017 N, respectively) and stiff (tendon rest length to muscle fiber length, LT:LMF=5.3 and 2.1, respectively), and are probably well adapted to stabilizing the carpus during the stance phase of gait. In contrast, the flexor carpi radialis muscle displayed long fibers (89.7 mm), low peak isometric force (Fmax=555 N), and high stiffness (LT:LMF=1.6). Due to its long fibers and low Fmax, flexor carpi radialis appears to be better adapted to flexion and extension of the limb during the swing phase of gait than to stabilization of the carpus during stance. Including muscle architectural parameters in a musculoskeletal model of the equine distal forelimb may lead to more realistic estimates not only of the magnitudes of muscle forces, but also of the distribution of forces among the muscles crossing any given joint.


Noninvasive diagnosis of coronary artery disease: the cardiokymographic stress test.
Stress-induced abnormalities of regional left ventricular wall motion were assessed by cardiokymography (CKG) during the course of maximal treadmill exercise tests in 157 patients, of whom 122 subsequently underwent coronary angiography. Seventy patients had significant angiographic coronary artery disease and 52 were normal. Forty-one of the 70 patients developed greater than 0.1 mV ST-segment depression (ECG sensitivity 59%) and 52 of 70 patients developed abnormal systolic outward motion by CKG (CKG sensitivity 74%). Among the 52 normals, 36 had negative ECG stress tests (ECG specificity 69%) and 49 had normally sustained systolic inward motion by CKG (CKG specificity 94%). The stress CKG was normal in 15 of the 16 false-positive stress ECGs; the stress ECG was correctly normal in two of the three false-positive stress CKG tests. Only one normal patient had concordantly false-positive ECG and CKG tests. The predictive accuracy of concordant ECG and CKG interpretations was, therefore, higher than either test alone. These data suggest that regional wall motion abnormalities, which are sensitive and specific markers of myocardial ischemia, may be detected noninvasively by CKG. We concluded that CKG helps identify false-positive and false-negative ECG stress tests and improves the diagnostic accuracy of stress testing for detection of coronary artery disease.


Association of prediabetes and diabetes with stroke symptoms: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms. This study included 25,696 individuals aged ≥ 45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003-2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire. The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18-1.39]) and two or more stroke symptoms (1.26 [1.12-1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03-1.29]), vision loss (1.52 [1.31-1.76]), half-vision loss (1.54 [1.30-1.84]), and lost ability to understand people (1.34 [1.12-1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms. In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.


Effect of Hospital Readmission Reduction on Patients at Low, Medium, and High Risk of Readmission in the Medicare Population.
Hospitalization and readmission rates have decreased in recent years, with the possible consequence that hospitals are increasingly filled with high-risk patients. We studied whether readmission reduction has affected the risk profile of hospitalized patients and whether readmission reduction was similarly realized among hospitalizations with low, medium, and high risk of readmissions. Retrospective study of hospitalizations between January 2009 and June 2015. Hospitalized fee-for-service Medicare beneficiaries, categorized into 1 of 5 specialty cohorts used for the publicly reported hospital-wide readmission measure. Each hospitalization was assigned a predicted risk of 30-day, unplanned readmission using a risk-adjusted model similar to publicly reported measures. Trends in monthly mean predicted risk for each cohort and trends in monthly observed to expected readmission for hospitalizations in the lowest 20%, middle 60%, and highest 20% of risk of readmission were assessed using time series models. Of 47,288,961 hospitalizations, 16.2% (n = 7,642,161) were followed by an unplanned readmission within 30 days. We found that predicted risk of readmission increased by 0.24% (P = .03) and 0.13% (P = .004) per year for hospitalizations in the surgery/ gynecology and neurology cohorts, respectively. We found no significant increase in predicted risk for hospitalizations in the medicine (0.12%, P = .12), cardiovascular (0.32%, P = .07), or cardiorespiratory (0.03%, P = .55) cohorts. In each cohort, observed to expected readmission rates steadily declined, and at similar rates for patients at low, medium, and high risk of readmission. Hospitals have been effective at reducing readmissions across a range of patient risk strata and clinical conditions. The risk of readmission for hospitalized patients has increased for 2 of 5 clinical cohorts.


Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight-loss diets in a 2-year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
Common genetic variants in the insulin receptor substrate 1 (IRS1) gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to 1 of 4 diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin (P=0.009), HOMA-IR (P=0.015), and weight loss (P=0.018) than those without this genotype in the highest-carbohydrate diet group whereas an opposite genotype effect on changes in insulin and HOMA-IR (P≤0.05) was observed in participants assigned to the lowest-carbohydrate diet group. No significant differences were observed across genotypes in the other 2 diet groups. The tests for genotype by intervention interactions were all significant (P<0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest-carbohydrate diet group (P<0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR (P for genotype-time interaction ≤0.009) in participants with the CC genotype than those without this genotype across 2-year intervention. Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet. http:www.clinicaltrials.gov. Unique identifier: NCT00072995.


Differences in perinatal and infant mortality in high-income countries: artifacts of birth registration or evidence of true differences?
Variation in birth registration criteria may compromise international comparisons of fetal and infant mortality. We examined the effect of birth registration practices on fetal and infant mortality rates to determine whether observed differences in perinatal and infant mortality rates were artifacts of birth registration or reflected true differences in health status. A retrospective population-based cohort study was done using data from Canada, United States, Denmark, Finland, Iceland, Norway, and Sweden from 1995-2005. Main outcome measures included live births by gestational age and birth weight; gestational age-and birth weight-specific stillbirth rates; neonatal, post-neonatal, and cause-specific infant mortality. Proportion of live births <22 weeks varied substantially: Sweden (not reported), Iceland (0.00%), Finland (0.001%), Denmark (0.01%), Norway (0.02%), Canada (0.07%) and United States (0.08%). At 22-23 weeks, neonatal mortality rates were highest in Canada (892.2 per 1000 live births), Denmark (879.3) and Iceland (1000.0), moderately high in the United States (724.1), Finland (794.3) and Norway (739.0) and low in Sweden (561.2). Stillbirth:live birth ratios at 22-23 weeks were significantly lower in the United States (79.2 stillbirths per 100 live births) and Finland (90.8) than in Canada (112.1), Iceland (176.2) and Norway (173.9). Crude neonatal mortality rates were 83% higher in Canada and 96% higher in the United States than Finland. Neonatal mortality rates among live births ≥ 28 weeks were lower in Canada and United States compared with Finland. Post-neonatal mortality rates were higher in Canada and United States than in Nordic countries. Live birth frequencies and stillbirth and neonatal mortality patterns at the borderline of viability are likely due to differences in birth registration practices, although true differences in maternal, fetal and infant health cannot be ruled out. This study emphasises the need for further standardisations, in order to enhance the relevance of international comparisons of infant mortality.


Source of endogenous arachidonate and 5-lipoxygenase products in human neutrophils stimulated by bradykinin and A23187.
The lipoxygenase products of arachidonic acid (AA) metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and leucotriene B4 (LTB4), are considered to have an important pathophysiological role in inflammatory bowel disease by stimulating the inflammatory response and by contributing to the diarrhoea. The present studies were designed to investigate the effect of the physiological stimulants bradykinin (BK) and 5-hydroxytryptamine (5-HT), in addition to the influence of the calcium ionophore A23187, on the source of AA release and 5-lipoxygenation in human neutrophils (PMNs) in vitro. This was done to elucidate the specificity of the mechanism by which PMNs respond to physiological, extracellular Ca2+ dependent agonists. The results of the study indicate that stimulation of 1-14C-AA-prelabelled PMNs with BK liberates AA mainly from phosphatidylinositol, while A23187 causes release of AA from phosphatidylcholine, phosphatidylethanolamine, and possibly phosphatidylserine. Furthermore BK (10(-9)-10(-6)M) dose-dependently stimulated the formation of 5-HETE and LTB4, reaching a maximum at 10(-7)M, while 5-HT (10(-8)-10(-4)M) released only negligible amounts of eicosanoids, similar to those observed in control experiments. Stimulation with A23187 (10(-5)M) caused a high release of both 5-HETE and LTB4. These results offer evidence that BK, but not 5-HT, initiates formation of lipoxygenase products by binding to specific receptors on the external surface of PMNs, whereas A23187 accelerates 5-lipoxygenation through mechanisms which do not involve a cell surface receptor.


Military body fat standards and equations applied to middle-aged women.
Military circumference equations are used to assess compliance of military personnel with body fat (BF) standards. The purpose of the present study was to determine the ability of military equations to correctly classify 62 women aged 40-60 yr (50.9 +/- 6.2, mean +/- SD) as overfat or underfat using underwater weighing (UWW) as the reference method and military BF standards as diagnostic cutoffs. Values for the mean +/- SD percent BF from UWW, Army, Marine Corps, and Navy equations were 29.5 +/- 7.1, 27.3 +/- 4.7, 25.7 +/- 5.8, and 30.3 +/- 5.1, respectively. The Army and Marine Corps equations underpredicted percent BF compared to UWW, P < 0.05. Bland-Altman plots showed a lack of agreement in predicting percent BF in women 40-60 yr between equation and UWW-derived percent BF. This finding was supported by the low agreement in correctly classifying an individual as meeting or exceeding the BF standards, range 25%-57%, Cohen's kappa. The low sensitivities (range 20%-74%) and higher specificities (range 80%-98%) of the equations indicated they identified individuals who met the BF standards better than those who exceeded them. Caution must be exercised when using military prediction equations to assess compliance with military BF standards in healthy middle-aged women.


An ensemble model of the male gonadal axis: illustrative application in aging men.
Testosterone (Te) production declines in the aging male, albeit for unknown reasons. Plausible mechanisms include reduced secretion of GnRH, less feedforward by LH, and/or altered feedback by systemic Te. The present study tests all three postulates in a cohort of 10 young (20-35 yr old) and eight older (50-72 yr old) men. The experimental paradigm comprised graded blockade of the GnRH receptor to create four distinct strata of LH and Te pulsatility in each subject. A novel analytical formalism was developed to reconstruct implicit dose-response functions linking 1) virtual GnRH outflow positively to LH secretion, 2) LH pulses positively to Te secretion, and 3) Te concentrations negatively to the size and number of LH secretory bursts. Validation was by direct pituitary sampling in the horse and sheep. Statistical comparisons disclosed that age decreased the efficacy of each of 1) virtual GnRH outflow (P < 0.01), 2) LH drive of Te secretion (P < 0.01), and 3) total, bioavailable and free Te feedback on GnRH-driven LH secretion (P = 0.015). In contrast, age increased the potency of virtual GnRH feedforward (P = 0.013) and did not affect Te's inhibition of LH pulse frequency. Unexplained variance was less than 10%. Robustness was shown by resampling techniques. Accordingly, competitive silencing of one locus of control and ensemble-based analyses identified triple regulatory deficits in the aging male gonadal axis. The generality of the present integrative model suggests utility in parsing interlinked adaptations in other physiological networks.


Issues relating to long-term follow-up in hip arthroplasty surgery: a review of 598 cases at 7 years comparing 2 prostheses using revision rates, survival analysis, and patient-based measures.
We reviewed 598 cemented Charnley and Hi-nek total hip arthroplasties at 7 years. Data were obtained from general practitioners, hospital medical notes, microfilm, and patient questionnaires. Outcome measures were revision rates, survival analysis, 12-item Oxford Hip Score, and satisfaction ratings. There were 471 Charnley (79%) and 127 Hi-nek (21%) total hip arthroplasties; 139 deaths (23%) occurred, and 5 (<1%) were lost to follow-up. Characteristics of the Charnley and Hi-nek patient groups were similar, with more information missing for Charnley cases. Revision rates were Charnley, 37 (8%), and Hi-nek, 6 (5%) (not significant). Survival analysis revealed no difference between the 2 groups (P = .23). The patients' median Oxford Hip Score was low/good (19), slightly worse for the Hi-nek group (not significant). Taking all evidence together, neither implant was outperforming the other at 7 years.


Efficacy and safety of low-carbohydrate diets: a systematic review.
Low-carbohydrate diets have been popularized without detailed evidence of their efficacy or safety. The literature has no clear consensus as to what amount of carbohydrates per day constitutes a low-carbohydrate diet. To evaluate changes in weight, serum lipids, fasting serum glucose, and fasting serum insulin levels, and blood pressure among adults using low-carbohydrate diets in the outpatient setting. We performed MEDLINE and bibliographic searches for English-language studies published between January 1, 1966, and February 15, 2003, with key words such as low carbohydrate, ketogenic, and diet. We included articles describing adult, outpatient recipients of low-carbohydrate diets of 4 days or more in duration and 500 kcal/d or more, and which reported both carbohydrate content and total calories consumed. Literature searches identified 2609 potentially relevant articles of low-carbohydrate diets. We included 107 articles describing 94 dietary interventions reporting data for 3268 participants; 663 participants received diets of 60 g/d or less of carbohydrates--of whom only 71 received 20 g/d or less of carbohydrates. Study variables (eg, number of participants, design of dietary evaluation), participant variables (eg, age, sex, baseline weight, fasting serum glucose level), diet variables (eg, carbohydrate content, caloric content, duration) were abstracted from each study. Two authors independently reviewed articles meeting inclusion criteria and abstracted data onto pretested abstraction forms. The included studies were highly heterogeneous with respect to design, carbohydrate content (range, 0-901 g/d), total caloric content (range, 525-4629 kcal/d), diet duration (range, 4-365 days), and participant characteristics (eg, baseline weight range, 57-217 kg). No study evaluated diets of 60 g/d or less of carbohydrates in participants with a mean age older than 53.1 years. Only 5 studies (nonrandomized and no comparison groups) evaluated these diets for more than 90 days. Among obese patients, weight loss was associated with longer diet duration (P =.002), restriction of calorie intake (P =.03), but not with reduced carbohydrate content (P =.90). Low-carbohydrate diets had no significant adverse effect on serum lipid, fasting serum glucose, and fasting serum insulin levels, or blood pressure. There is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.


Prenatal marijuana exposure and neonatal outcomes in Jamaica: an ethnographic study.
To identify neurobehavioral effects of prenatal marijuana exposure on neonates in rural Jamaica. Ethnographic field studies and standardized neuro-behavior assessments during the neonatal period. Rural Jamaica in heavy-marijuana-using population. Twenty-four Jamaican neonates exposed to marijuana prenatally and 20 nonexposed neonates. Exposed and nonexposed neonates were compared at 3 days and 1 month old, using the Brazelton Neonatal Assessment Scale, including supplementary items to capture possible subtle effects. There were no significant differences between exposed and nonexposed neonates on day 3. At 1 month, the exposed neonates showed better physiological stability and required less examiner facilitation to reach organized states. The neonates of heavy-marijuana-using mothers had better scores on autonomic stability, quality of alertness, irritability, and self-regulation and were judged to be more rewarding for caregivers. The absence of any differences between the exposed on nonexposed groups in the early neonatal period suggest that the better scores of exposed neonates at 1 month are traceable to the cultural positioning and social and economic characteristics of mothers using marijuana that select for the use of marijuana but also promote neonatal development.


Somatic Cell Count: A Human Breast Wellbeing Indicator.
Human milk is universally accounted as the preeminent source of nutrition for infants. Surprisingly, no approved diagnostic tests are available for the diagnosis of physical condition of the breast. Somatic cell count (SCC) is a key tool commonly used in the dairy industry to provide evidence of udder health, which in turn determines the quality of bovine and cattle milk. Elevated levels of somatic cells in milk are observed during intra-mammary infectious state in bovine animals, which is due to active participation of the immune system. This constraint in humans can principally be used to study breast health. In the present study, 176 breast milk samples in total were randomly collected from four different regions of Gujarat, India. All the samples were subjected to somatic cell count and total bacterial count tests. The effect of geographical region and maternal health was studied on the basis of milk SCC and total bacterial load. Statistical interpretation of the results was done using PRISM 6.07. Breast showing clinical symptoms of mastitis yielded a high SCC (>104 cells/microliter (μL)) and bacterial count (between 105 to 1011 Colony Forming Unit (CFU)/milliliter (mL)) in comparison to milk collected from healthy breast (<104 cells/μL and 103 to 104 CFU/mL). Statistical analysis reveals existence of significant correlation between the geographical region and SCC count of milk collected from healthy breast whereas no correlation was observed in infected breast milk. The study has also demonstrated that a lineer correlation exists between SCC and abundance of bacteria present in breast milk. The present study could be employed to predict lactating breast health.


The neutrophil-to-lymphocyte ratio as a marker of systemic endothelial dysfunction in asymptomatic subjects.
The neutrophil-to-lymphocyte ratio has demonstrated to be a prognostic inflammatory marker in cardiovascular disease. The objective of this study is to evaluate the association between neutrophil-to-lymphocyte ratio and pathologic urinary albumin/creatinine ratio as an early marker of cardiovascular risk and systemic endothelial dysfunction, associated with microvascular disease, in asymptomatic subjects. A unicenter cross-sectional study was conducted, including 1816 asymptomatic subjects. Patients with previous cardiovascular disease, those who were treated with ACE inhibitors and/or angiotensin II receptor blockers and patients with albumin/creatinine ratio over 300mg/g were excluded. The outcome of the study was the presence of a pathologic urinary albumin/creatinine ratio. The neutrophil-to-lymphocyte ratio was significantly associated with altered urinary albumin/creatinine ratio in the univariate analysis and after adjustment for other known endothelial and cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes or altered glomerular filtration rate). Based on the sensitivity and specificity of different neutrophil-to-lymphocyte ratio thresholds, 3 risk groups were created for altered urinary albumin/creatinine ratio: low risk in those with neutrophil-to-lymphocyte ratio < 1.5, intermediate risk in patients between 1.5 and 3, and high risk in those with neutrophil-to-lymphocyte ratio > 3. These groups were found to have a statistically significant and independent prognostic power for altered urinary albumin/creatinine ratio in asymptomatic patients. The neutrophil-to-lymphocyte ratio appears to be a cost-efficient, non-invasive and independent potential marker of systemic endothelial dysfunction in asymptomatic subjects.


Racial/ethnic disparities in survival among men diagnosed with prostate cancer in Texas.
To the authors' knowledge, few studies to date have examined racial differences in prostate cancer survival while controlling for socioeconomic status (SES). No such studies have examined this association in Texas, a large state with significant ethnic and racial diversity. The objective of this analysis was to determine whether racial disparities in survival for men diagnosed with prostate cancer in Texas from 1995 through 2002 remained after adjusting for SES, rural residence, and stage of disease. A cohort of 87,449 men who were diagnosed with prostate cancer was identified from the Texas Cancer Registry. The SES measure was based on census tract data reflecting median household income, median home value, and percentages of men living below poverty, with a college education, and with a management or professional occupation. The 5-year survival rates were calculated using the Kaplan-Meier method and Cox proportional hazard modeling was used to estimate hazard ratios (HRs) for race and all-cause and disease-specific mortality. After adjusting for SES, age, stage of disease, tumor grade, year of diagnosis, and rural residence, both black and Hispanic men were more likely (adjusted HR [aHR], 1.70 [95% confidence interval (95% CI), 1.58-1.83] and aHR, 1.11 [95% CI, 1.02-1.20], respectively) to die of prostate cancer compared with white men. The pattern of survival disadvantage for black men held for those diagnosed with localized disease and advanced disease, and for those with an unknown stage of disease at diagnosis. Substantial racial disparities in prostate cancer survival were found for men in Texas. Future studies should incorporate treatment data as well as comorbid conditions because this information may explain noted survival disparities.


The nanoscale phase distinguishing of PCL-PB-PCL blended in epoxy resin by tapping mode atomic force microscopy.
In this work, we investigated the bulk phase distinguishing of the poly(ε-caprolactone)-polybutadiene-poly(ε-caprolactone) (PCL-PB-PCL) triblock copolymer blended in epoxy resin by tapping mode atomic force microscopy (TM-AFM). We found that at a set-point amplitude ratio (rsp) less than or equal to 0.85, a clear phase contrast could be obtained using a probe with a force constant of 40 N/m. When rsp was decreased to 0.1 or less, the measured size of the PB-rich domain relatively shrank; however, the height images of the PB-rich domain would take reverse (translating from the original light to dark) at rsp = 0.85. Force-probe measurements were carried out on the phase-separated regions by TM-AFM. According to the phase shift angle vs. rsp curve, it could be concluded that the different force exerting on the epoxy matrix or on the PB-rich domain might result in the height and phase image reversion. Furthermore, the indentation depth vs. rsp plot showed that with large tapping force (lower rsp), the indentation depth for the PB-rich domain was nearly identical for the epoxy resin matrix.


A primal-dual active-set method for non-negativity constrained total variation deblurring problems.
This paper studies image deblurring problems using a total variation-based model, with a non-negativity constraint. The addition of the non-negativity constraint improves the quality of the solutions, but makes the solution process a difficult one. The contribution of our work is a fast and robust numerical algorithm to solve the non-negatively constrained problem. To overcome the nondifferentiability of the total variation norm, we formulate the constrained deblurring problem as a primal-dual program which is a variant of the formulation proposed by Chan, Golub, and Mulet for unconstrained problems. Here, dual refers to a combination of the Lagrangian and Fenchel duals. To solve the constrained primal-dual program, we use a semi-smooth Newton's method. We exploit the relationship between the semi-smooth Newton's method and the primal-dual active set method to achieve considerable simplification of the computations. The main advantages of our proposed scheme are: no parameters need significant adjustment, a standard inverse preconditioner works very well, quadratic rate of local convergence (theoretical and numerical), numerical evidence of global convergence, and high accuracy of solving the optimality system. The scheme shows robustness of performance over a wide range of parameters. A comprehensive set of numerical comparisons are provided against other methods to solve the same problem which show the speed and accuracy advantages of our scheme.


Preparation and characterization of bovine serum albumin surface-imprinted thermosensitive magnetic polymer microsphere and its application for protein recognition.
A novel bovine serum albumin surface-imprinted thermosensitive magnetic composite microsphere was successfully prepared by the surface grafting copolymerization method in the presence of temperature-sensitive monomer N-isopropylacrylamide (NIPAM), functional monomer methacrylic acid (MAA) and cross-linking agent N,N'-methylenebisacrylamide (MBA). The structure and component of the thermosensitive magnetic molecularly imprinted microsphere were investigated by transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The results of thermosensitivity, adsorption capacity, selectivity and reusability showed the formation of a thermosensitivity grafting polymer layer P(NIPAM-MAA-MBA) on the surface of Fe3O4@SiO2 and the good adsorption capacity and specific recognition for template protein. When the adsorption temperature was higher than the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM), shape memory effect of imprinted cavities would be more effective. In other words, it was more conducive to capture template molecules under this condition and the imprinting factor would be higher. On the other hand, when the desorption temperature was lower than LCST of PNIPAM, the decrease of shape memory effect between imprinted cavities and template molecules would facilitate the release of template molecules from the imprinted cavities. Based on this property, the adsorption and desorption of template molecules could be regulated by system temperature indirectly which benefited from the existence of thermosensitivity imprinting layer.


Exploring the Link between Nucleosome Occupancy and DNA Methylation.
Near promoters, both nucleosomes and CpG sites form characteristic spatial patterns. Previously, nucleosome depleted regions were observed upstream of transcription start sites and nucleosome occupancy was reported to correlate both with CpG density and the level of CpG methylation. Several studies imply a causal link where CpG methylation might induce nucleosome formation, whereas others argue the opposite, i.e., that nucleosome occupancy might influence CpG methylation. Correlations are indeed evident between nucleosomes, CpG density and CpG methylation-at least near promoter sites. It is however less established whether there is an immediate causal relation between nucleosome occupancy and the presence of CpG sites-or if nucleosome occupancy could be influenced by other factors. In this work, we test for such causality in human genomes by analyzing the three quantities both near and away from promoter sites. For data from the human genome we compare promoter regions with given CpG densities with genomic regions without promoters but of similar CpG densities. We find the observed correlation between nucleosome occupancy and CpG density, respectively CpG methylation, to be specific to promoter regions. In other regions along the genome nucleosome occupancy is statistically independent of the positioning of CpGs or their methylation levels. Anti-correlation between CpG density and methylation level is however similarly strong in both regions. On promoters, nucleosome occupancy is more strongly affected by the level of gene expression than CpG density or CpG methylation-calling into question any direct causal relation between nucleosome occupancy and CpG organization. Rather, our results suggest that for organisms with cytosine methylation nucleosome occupancy might be primarily linked to gene expression, with no strong impact on methylation.


PC1/3 Deficiency Impacts Pro-opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons.
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. The increased levels of unprocessed POMC and the decreased ratios (relative to POMC) of processed POMC-derived peptides in both PCSK1 knockdown and knockout hESC-derived neurons phenocopied POMC processing reported in PC1/3-null mice and PC1/3-deficient patients. PC1/3 deficiency was associated with increased expression of melanocortin receptors and PRCP (prolylcarboxypeptidase, a catabolic enzyme for α-melanocyte stimulating hormone (αMSH)), and reduced adrenocorticotropic hormone secretion. We conclude that the obesity accompanying PCSK1 deficiency may not be primarily due to αMSH deficiency.


The next generation of transcription factor binding site prediction.
Finding where transcription factors (TFs) bind to the DNA is of key importance to decipher gene regulation at a transcriptional level. Classically, computational prediction of TF binding sites (TFBSs) is based on basic position weight matrices (PWMs) which quantitatively score binding motifs based on the observed nucleotide patterns in a set of TFBSs for the corresponding TF. Such models make the strong assumption that each nucleotide participates independently in the corresponding DNA-protein interaction and do not account for flexible length motifs. We introduce transcription factor flexible models (TFFMs) to represent TF binding properties. Based on hidden Markov models, TFFMs are flexible, and can model both position interdependence within TFBSs and variable length motifs within a single dedicated framework. The availability of thousands of experimentally validated DNA-TF interaction sequences from ChIP-seq allows for the generation of models that perform as well as PWMs for stereotypical TFs and can improve performance for TFs with flexible binding characteristics. We present a new graphical representation of the motifs that convey properties of position interdependence. TFFMs have been assessed on ChIP-seq data sets coming from the ENCODE project, revealing that they can perform better than both PWMs and the dinucleotide weight matrix extension in discriminating ChIP-seq from background sequences. Under the assumption that ChIP-seq signal values are correlated with the affinity of the TF-DNA binding, we find that TFFM scores correlate with ChIP-seq peak signals. Moreover, using available TF-DNA affinity measurements for the Max TF, we demonstrate that TFFMs constructed from ChIP-seq data correlate with published experimentally measured DNA-binding affinities. Finally, TFFMs allow for the straightforward computation of an integrated TF occupancy score across a sequence. These results demonstrate the capacity of TFFMs to accurately model DNA-protein interactions, while providing a single unified framework suitable for the next generation of TFBS prediction.


Theory and computation of photopolymerization-induced phase transition and morphology development in blends of crystalline polymer and photoreactive monomer.
A hypothetical phase diagram of a crystalline polymer/photoreactive monomer mixture has been calculated on the basis of phase field (PF) free energy of crystal solidification in conjunction with Flory-Huggins (FH) free energy of liquid-liquid demixing to guide the morphology development during photopolymerization of poly(ethylene oxide)/triacrylate blend. The self-consistent solution of the combined PF-FH theory exhibits a crystalline-amorphous phase diagram showing the coexistence of solid+liquid gap bound by the liquidus and solidus lines, followed by an upper critical solution temperature at a lower temperature. When photopolymerization was triggered in the isotropic region, i.e., slightly above the crystal melting transition temperatures, the depressed melting transition line moves upward. When it surpasses the reaction temperature, both crystallization and phase separation occur. The temporal evolution of phase morphology is examined in the context of time-dependent Ginzburg-Landau equations coupled with the energy balance (heat conduction) equation using the aforementioned PF-FH free-energy densities. Of particular interest is that the emerged morphology in the crystalline blends depends on the competition between dynamics of liquid-liquid phase separation and/or liquid-solid phase transition (i.e., crystallization) and photopolymerization rates.


Measurement of the Soft-Drop Jet Mass in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.
Jet substructure observables have significantly extended the search program for physics beyond the standard model at the Large Hadron Collider. The state-of-the-art tools have been motivated by theoretical calculations, but there has never been a direct comparison between data and calculations of jet substructure observables that are accurate beyond leading-logarithm approximation. Such observables are significant not only for probing the collinear regime of QCD that is largely unexplored at a hadron collider, but also for improving the understanding of jet substructure properties that are used in many studies at the Large Hadron Collider. This Letter documents a measurement of the first jet substructure quantity at a hadron collider to be calculated at next-to-next-to-leading-logarithm accuracy. The normalized, differential cross section is measured as a function of log_{10}ρ^{2}, where ρ is the ratio of the soft-drop mass to the ungroomed jet transverse momentum. This quantity is measured in dijet events from 32.9 fb^{-1} of sqrt[s]=13 TeV proton-proton collisions recorded by the ATLAS detector. The data are unfolded to correct for detector effects and compared to precise QCD calculations and leading-logarithm particle-level Monte Carlo simulations.


Progress towards eliminating lymphatic filariasis in Zanzibar: a model programme.
Programmes to eliminate lymphatic filariasis are underway in ten countries of sub-Saharan Africa, and in several programmes outside Africa five rounds of mass drug administration (MDA) are being completed. In Africa, Egypt and Zanzibar have completed five rounds of MDA. Zanzibar was the first country to complete five rounds of treatment using a combination of albendazole and ivermectin, reducing both the prevalence and intensity of Wuchereria bancrofti. Characteristics of the Zanzibar programme serve as a model for other countries: factors crucial to its success include high-level political commitment, the development of appropriate social mobilization strategies, the involvement of communities in drug distribution, and the introduction of morbidity management for individuals with lymphoedema.


Observation of Weyl fermions in a magnetic non-centrosymmetric crystal.
The absence of inversion symmetry in non-centrosymmetric materials has a fundamental role in the emergence of a vast number of fascinating phenomena, like ferroelectricity, second harmonic generation, and Weyl fermions. The removal of time-reversal symmetry in such systems further extends the variety of observable magneto-electric and topological effects. Here we report the striking topological properties in the non-centrosymmetric spin-orbit magnet PrAlGe by combining spectroscopy and transport measurements. By photoemission spectroscopy below the Curie temperature, we observe topological Fermi arcs that correspond to projected topological charges of ±1 in the surface Brillouin zone. In the bulk, we observe the linear energy-dispersion of the Weyl fermions. We further observe a large anomalous Hall response in our magneto-transport measurements, which is understood to arise from diverging bulk Berry curvature fields associated with the Weyl band structure. These results establish a novel Weyl semimetal phase in magnetic non-centrosymmetric PrAlGe.


Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection.
The inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. Using recently described "depletion of regulatory T cell" (DEREG) mice, we found that selective depletion of regulatory T cells (Tregs) during acute respiratory syncytial virus (RSV) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, and T-cell activation and cellular influx into the lungs. Conversely, inflammation was decreased when Treg numbers and activity were boosted using interleukin-2 immune complexes. Unexpectedly, lung (but not draining lymph node) Tregs from RSV-infected mice expressed granzyme B (GzmB), and bone marrow chimeric mice with selective loss of GzmB in the Treg compartment displayed markedly enhanced cellular infiltration into the lung after infection. A crucial role for GzmB-expressing Tregs has not hitherto been described in the lung or during acute infections, but may explain the inability of children with perforin/GzmB defects to regulate immune responses to infection. The effects of RSV infection in mice with defective immune regulation closely parallel the observed effects of RSV in children with bronchiolitis, suggesting that the pathogenesis of bronchiolitis may involve an inability to regulate virus-induced inflammation.


Observations on the water distribution and extractable sugar content in carrot slices after pulsed electric field treatment.
The impact of pulsed electric field (PEF) processing conditions on the distribution of water in carrot tissue and extractability of soluble sugars from carrot slices was studied. Time domain NMR relaxometry was used to investigate the water proton mobility in PEF-treated carrot samples. Three distinct transverse relaxation peaks were observed in untreated carrots. After PEF treatment only two slightly-overlapping peaks were found; these were attributed to water present in the cytoplasm and vacuole of carrot xylem and phloem tissues. This post-treatment observation indicated an increase in water permeability of tissues and/or a loss of integrity in the tonoplast. In general, the stronger the electric field applied, the lower the area representing transverse relaxation (T2) values irrespective of treatment duration. Moreover an increase in sucrose, β- and α-glucose and fructose concentrations of carrot slice extracts after PEF treatment suggested increases in both cell wall and vacuole permeability as a result of exposure to pulsed electric fields.


The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study.
There is a growing body of evidence indicating that chronic alcohol consumption induces morphological changes in the central nervous system (CNS) similar to those observed during brain senescence, including an increased formation of lipofuscin. In addition, it was also found that alcohol withdrawal does not reverse these changes. On the contrary, most of the alterations observed during alcohol consumption worsen as happens with the increased lipofuscin formation. Thus, using our model of alcohol feeding and withdrawal, we decided to examine the effects of different drugs said to offer neuronal protection during CNS degenerative processes. The action of piracetam, a cyclic derivate of GABA and commonly used as a nootropic agent, was tested by studying the lipofuscin accumulation on the cerebellar Purkinje and hippocampal CA3 pyramidal cells in alcohol-treated and withdrawn rats. Piracetam was found to markedly decrease the formation of neuronal lipofuscin. Whatever the functional implications of this pigment, its reduction in piracetam-treated animals might be related either to a protective effect on the intraneuronal membranous system or to an antioxidant property of this molecule.


Role of injectable collagen in the treatment of glottic insufficiency: a study of 119 patients.
Injectable bovine collagen has been used for treatment of glottic insufficiency at the University of Wisconsin Clinical Science Center since 1983. This report reviews our experience in treating 119 patients with a variety of vocal fold disorders manifested by glottic insufficiency. Many of the patients were referred because of prior treatment failures or problems that were impossible to treat with other modalities. Results were assessed by comprehensive voice evaluations using subjective patient self-assessments, perceptual judgments made by a panel of experts who had no prior knowledge of the study, objective assessments, and videostroboscopy. Objective assessment included vocal function measures and acoustic analysis. Results indicate that collagen not only is comparable to other injection filler substances but also has unique advantages as a bioimplant. Collagen injection seems uniquely suited for treatment of several problems, including vocal fold atrophy, focal defects, minimal glottic insufficiency, and scarred vocal folds that are not managed optimally with Teflon injection. Overall there were no serious complications and treatment was effective for a broad spectrum of problems. In most instances the correction persisted, and in those instances in which injected collagen seemed improperly distributed, the vocal fold was recontoured or the implant removed without appreciable damage to the surrounding tissues. Injectable collagen has been extensively studied and deserves to be included in the armamentarium of the laryngeal surgeon.


Deprotecting thioacetyl-terminated terphenyldithiol for assembly on gallium arsenide.
We characterize the assembly of terphenyldithiol (TPDT) on gallium arsenide (GaAs) from ethanol (EtOH) and tetrahydrofuran (THF) as a function of ammonium hydroxide (NH4OH) concentration. NH4OH facilitates the conversion of thioacetyl end groups of the TPDT precursor to thiolates in the assembly solution. The final structure of TPDT assembled on GaAs is sensitive not only to the assembly solvent but also to NH4OH concentration. In the presence of low concentrations of NH4OH (1 mM), TPDT assemblies from EtOH are oriented upright. The same assemblies are less upright when adsorption is carried out at higher NH4OH concentrations. In THF, TPDT does not adsorb significantly on GaAs at low NH4OH concentrations. The surface coverage and structural organization of these assemblies improve with increasing NH4OH concentrations, although these assemblies are never as organized as those from EtOH. The difference in the final structure of TPDT assemblies is attributed to differences in the thiolate fraction in the assembly solution at the point of substrate immersion.


Retinal Vein Occlusion in Benin City, Nigeria.
Retinal vein occlusion (RVO) is the most common occlusive retinal vascular disorder and results in varying degrees of visual loss. To determine the pattern of presentation, risk factors, and treatment outcomes in a group of patients with RVO seen in a tertiary hospital in Nigeria. Medical records of patients who presented to the University of Benin Teaching Hospital, Benin City, Nigeria in whom a diagnosis of RVO was made over a 5 years period were reviewed. Data obtained were analyzed with the GraphPad Instat Software, Inc. version V2.05a program, San Diego, Califonia and a P < 0.05 considered significant. There were 20 patients made of 14 (70.0%) males and 6 (30.0%) females with a mean age of 62.7 ± 10.4 years. There were 15 (68.2%) eyes with central RVO, 3 (13.6%) eyes with branch RVO, and 4 (18.2%) eyes with hemi RVO. Bilateral involvement occurred in 2 (10.0%) patients. Risk factors included hypertension 14 (70.0%), diabetes mellitus 9 (45.0%), and glaucoma 5 (22.7%). Multiple risk factors were present in 14 (70.0%) patients. Complications included macula edema 15 (68.2%), retinal neovascularization 5 (22.7%), neovascular glaucoma 3 (13.6%), and vitreous hemorrhage 2 (9.1%). Eyes which had definitive treatment with intravitreal antivascular endothelial growth factors and laser photocoagulation for macula edema and retinal neovascularization, respectively, had better visual acuity compared to eyes which did not receive these treatment, P = 0.002. The incidence and visual loss that occurs from RVO can be reduced by modifying known risk factors and early institution of appropriate therapy for complications that occur.


Integrative modelling of cellular assemblies.
A wide variety of experimental techniques can be used for understanding the precise molecular mechanisms underlying the activities of cellular assemblies. The inherent limitations of a single experimental technique often requires integration of data from complementary approaches to gain sufficient insights into the assembly structure and function. Here, we review popular computational approaches for integrative modelling of cellular assemblies, including protein complexes and genomic assemblies. We provide recent examples of integrative models generated for such assemblies by different experimental techniques, especially including data from 3D electron microscopy (3D-EM) and chromosome conformation capture experiments, respectively. We highlight general concepts in integrative modelling and discuss the need for careful formulation and merging of different types of information.