Birth rights and rituals in rural south India: care seeking in the intrapartum period.
Maternal morbidity and mortality are high in the Indian context, but the majority of maternal deaths could be avoided by prompt and effective access to intrapartum care (WHO, 1999). Understanding the care seeking responses to intrapartum morbidities is crucial if maternal health is to be effectively improved, and maternal mortality reduced. This paper presents the results of a prospective study of 388 women followed through delivery and traditional postpartum in rural Karnataka in southern India. In this setting, few women use the existing health facilities and most deliveries occur at home. The analysis uses quantitative data, collected via questionnaires administered to women both during pregnancy and immediately after delivery. By virtue of its prospective design, the study gives a unique insight into intentions for intrapartum care during pregnancy as well as events following morbidities during labour. Routine care in the intrapartum period, both within institutions and at home, and impediments to appropriate care are also examined. The study was designed to collect information about health seeking decisions made by women and their families as pregnancies unfolded, rather than trying to capture women's experience from a retrospective instrument. The data set is therefore a rich source of quantitative information, which incorporates details of event sequences and health service utilization not previously collected in a Safe Motherhood study. Additional qualitative information was also available from concurrent in-depth interviews with pregnant women, their families, health care providers and other key informants in the area. The level of unplanned institutional care seeking during the intrapartum period within the study area was very high, increasing from 11% planning deliveries at a facility to an eventual 35% actually delivering in hospitals. In addition there was a significant move away from planned deliveries with the auxiliary nurse midwive (ANM), to births with a lay attendant or dai. The proportion of women who planned for an ANM to assist was 49%, as compared with the actual occurrence, which was less than half of this proportion. Perceived quality of care was found to be an important factor in health seeking behaviour, as was wealth, caste, education and experience of previous problems in pregnancy. Actual care given by a range of practitioners was found to contain both beneficial and undesirable elements. As a response to serious morbidities experienced within the study period, many women were able to seek care although sometimes after a long delay. Those women who experienced inadequate progression of labour pains were most likely to proceed unexpectedly to a hospital delivery.


Continuum of hospital care: the role of intensive care.
This review outlines the way the specialty of intensive care has expanded over the last decade in response to the changing population of hospital patients, being older with more comorbidities and having more complex interventions. The previous disjointed professional and geographical silos, providing patient care, are being challenged and a more patient focussed continuum of care is replacing it. There have been many reports over the last few years, describing patient centred systems, constructed around the needs of the seriously ill, at-risk patient, including trauma systems and Medical Emergency Team-type systems. There is now general agreement that in most settings these systems are responsible for a significant reduction in mortality and serious adverse events such as cardiac arrest rates. The implications for the move towards systems to improve patient outcome and decrease mortality in hospitals are having a significant impact on the way we practise medicine, resulting in an emphasis, among other things, of constructing our care around the needs of patients, rather than rigidly practice medicine from within our own tribal boundaries, for example professional boundaries, medical specialty boundaries and geographical boundaries.


Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy.
Mutations in A-type nuclear lamins cause dilated cardiomyopathy, which is postulated to result from dysregulated gene expression due to changes in chromatin organization into active and inactive compartments. To test this, we performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared with gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal topology are evident, differences in chromatin compartmentalization are limited to a few hotspots that escape segregation to the nuclear lamina and inactivation during cardiogenesis. These regions exhibit up-regulation of multiple noncardiac genes including CACNA1A, encoding for neuronal P/Q-type calcium channels. Pharmacological inhibition of the resulting current partially mitigates the electrical alterations. However, chromatin compartment changes do not explain most gene expression alterations in mutant hiPSC-CMs. Thus, global errors in chromosomal compartmentation are not the primary pathogenic mechanism in heart failure due to lamin A/C haploinsufficiency.


Is the routine examination of surgical specimens worthwhile in primary total knee arthroplasty?
Two thousand two hundred eighty-nine consecutive primary total knee arthroplasties performed between 1993 and 1996 were reviewed retrospectively to assess the utility and cost effectiveness of the routine examination of surgical specimens. In those cases where a discrepancy was seen between the clinical and pathologic diagnoses, the records were reviewed carefully and those patients were contacted to determine whether their subsequent treatment was altered as a result of the pathologic findings. In 10 cases there was a potentially important discrepancy between the clinical and pathologic diagnoses. In none of those 10 cases was the subsequent treatment of the patient altered as a result of the pathologic findings. This study suggests a reexamination of regulations that mandate the routine pathologic review of surgical specimens from primary total knee arthroplasties.


Borrowed alleles and convergence in serpentine adaptation.
Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment.


[Factors which affect the progression and severity of Acanthamoeba keratitis].
To detect factors which affect the severity of Acanthamoeba keratitis. Patients diagnosed as having Acanthamoheba keratitis in our hospital from 2005 to 2009 were divided into two groups according to the severity, i.e., mild and severe. The days needed for the diagnosis, age, sex and the application of topical steroids were analyzed in each group. Forty-four eyes of 41 patients were involved; 33 eyes were diagnosed as mild and 11 eyes as severe types of Acanthamoeba keratitis. The average number of days from the initial symptoms was 19.8 in the mild and 15.1 in the severe type, and the average ages were 25.2 and 40.4 respectively. Topical steroids before the diagnosis of Acanthamoeba keratitis were applied in 72.7% of the severe cases and in 36.4% of the mild cases. The severity of Acanthamoeba keratitis was not directly related to the period from the initial symptoms, instead, some patients showed a rapid progression. Older age and the application of topical steroids before the diagnosis should be considered in rapidly progressive Acanthamoeba keratitis.


Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma.
Protein ubiquitylation coordinates crucial cellular events in physiological and pathological conditions. A comparative analysis of the ubiquitin proteome from bortezomib (BTZ)-sensitive and BTZ-resistant mantle cell lymphoma (MCL) revealed an enrichment of the autophagy-lysosome system (ALS) in BTZ-resistant cells. Pharmacological inhibition of autophagy at the level of lysosome-fusion revealed a constitutive activation of proteaphagy and accumulation of proteasome subunits within autophagosomes in different MCL cell lines with acquired or natural resistance to BTZ. Inhibition of the autophagy receptor p62/SQSTM1 upon verteporfin (VTP) treatment disrupted proteaphagosome assembly, reduced co-localization of proteasome subunits with autophagy markers and negatively impacted proteasome activity. Finally, the silencing or pharmacological inhibition of p62 restored the apoptosis threshold at physiological levels in BTZ-resistant cells both in vitro and in vivo. In total, these results demonstrate for the first time a proteolytic switch from the ubiquitin-proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, pointing out a crucial role for proteaphagy in this phenomenon and paving the way for the design of alternative therapeutic venues in treatment-resistant tumors.


Knowledge and attitudes towards use of long acting reversible contraceptives among women of reproductive age in Lubaga division, Kampala district, Uganda.
Uganda has one of the highest total fertility rates globally and in Sub-Saharan Africa. Her high fertility is mainly attributed to the high unmet need for family planning. Use of Long-acting reversible contraceptives (LARC) is low (13%) in Uganda yet they are the most cost-effective contraceptives. This study aimed to assess the reproductive aged women's knowledge, attitudes, and factors associated with use of LARC. A cross-sectional study was conducted involving 565 women (15-49 years) attending private and public health facilities in Lubaga division, Kampala district. Semi-structured questionnaires were used to measure knowledge, attitudes and factors associated with use of LARC; Intra-Uterine Devices, Implants and Injectables. The outcome variable was current use of LARC. A generalized linear regression model was run in STATA version12.0. Prevalence Risk Ratios for associations between current LARC use and independent factors were obtained and regarded significant at 95% CI with p < 0.05. Mean age (SD) and current use of LARC was 26.34 (5.35) and 31.7% respectively. Factors associated with current use of LARC were; previous use adj.PRR 2.89; (95% CI 2.29, 3.81), knowledge of implant administration site adj.PRR 1.83; (95% CI 1.17, 2.87), and perception that; male partner decisions positively influence their contraceptive choices adj.PRR 1.49; (95% CI 1.18, 1.88). Contrary, perception that LARC should be used by married women was negatively associated with use of LARC adj.PRR 0.63; (95% CI 0.44, 0.90). Knowledge about site of administration, previous use of LARC and women's attitude that male partners' choice influence their contraceptive decisions were positively associated with current use of LARC. Contrary, the attitude that LARC was for married women was negatively associated with its use. This study suggests a need to strengthen client education about LARC to dispel possible myths and to consider integrating male partner's decision making in contraceptive choices for women.


Changes in thermal homeostasis in humans due to repeated cold water immersions.
The purpose of this study was to monitor changes in body and skin temperatures, heat production, subjective shivering, cold sensation and body fat content in humans after intermittent cold water immersion. Repeated exposures of young sportsmen to cold water (head out, 14 degrees C, 1 h, 3 times per week for 4-6 weeks) induced changes in regulation of thermal homeostasis. "Cold acclimated" subjects exhibited an hypothermic type of adaptation. Central and peripheral body temperatures at rest and during cold immersion were lowered. The metabolic response to cold was delayed and subjective shivering was attenuated. The observed hypothermia was due to the shift of the threshold for induction of cold thermogenesis to lower body temperatures. "Cold acclimated" subjects also showed a lowered cold sensation. Because of the observed physiological changes, about 20% of the total heat production was saved during one cold water immersion of "cold acclimated" subjects. Maximal aerobic and anaerobic performances were not altered. No change in the thermosensitivity of the body temperature controller, as assessed from the unchanged slope of the relation between the deep body temperature and total heat production, was observed. Changes in cold sensation and regulation of cold thermogenesis were noticed first after four cold water immersions and persisted for at least 2 weeks after termination of the adaptation procedure. A trend towards a small increase in the body fat content was also observed. This finding, as well as the increased vasoconstriction, evidenced by the lowered skin temperature, indicate that slight changes in body insulation may also occur after "cold acclimation" in humans.


Aorta-to-right ventricular fistula due to pectus bar migration.
A 23-year-old man, operated on for pectus excavatum with a modified Ravitch procedure, was admitted to our emergency department suffering from severe dyspnea. Massive pericardial effusion, rupture of the sinus of Valsalva, and aortic-to-right ventricular fistula were present on echocardiography. Cardiac penetration of the metal bar was detected on chest CT scan. The defect at the right sinus of Valsalva was closed with a PTFE patch, and the right aortic and ventricular ruptures were repaired primarily.


Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group.
To determine whether treatment with dexamethasone and ceftriaxone for children with bacterial meningitis reduces the frequency of either sensorineural hearing loss or other neurologic sequelae. This was a prospective, multicentered, placebo-controlled clinical trial. Subjects were followed for 1 year. The study was conducted in six children's hospitals located in Pittsburgh, Houston, Los Angeles, Chicago, Washington, D.C., and Columbus, Ohio. Enrolled were 173 children, 8 weeks to 12 years of age, with suspected bacterial meningitis; 143 children were evaluable. Eighty-seven percent of patients were followed for at least 6 weeks to 3 months, and 67% were followed for 1 year. Subjects were randomized to receive ceftriaxone with or without dexamethasone (0.15 mg/kg every 6 hours for 4 days). Auditory brainstem responses (ABR) were measured within 24 hours of admission. Hearing, development, and neurologic sequelae were assessed at the time of discharge and 6 weeks and 1 year later. One hundred forty-three patients (69 received dexamethasone and 74 received placebo) with bacterial meningitis were evaluable: Haemophilus influenzae type b (83), Streptococcus pneumoniae (33), Neisseria meningitidis (24), and three others. Overall, there was no significant difference in auditory outcome between dexamethasone and placebo recipients. Twenty-two children had bilateral moderate or more severe hearing loss at the time of the first ABR. At follow-up, the resolution of hearing impairment was nearly identical for each group. Nine of ten children who remained persistently deaf were deaf at the time of the first ABR. There were no differences in neurologic or developmental outcome between groups. All but one child with persistent bilateral moderate or more severe hearing loss had demonstrable deafness at the time of the first ABR. Dexamethasone did not significantly improve audiologic, neurologic, or developmental outcome in children with bacterial meningitis.


Arsenic exposure affects plasma insulin-like growth factor 1 (IGF-1) in children in rural Bangladesh.
Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations. Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L) was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02) or weight (β=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (β=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03) was obtained above the median split. The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.


Nutritional and safety assessments of foods and feeds nutritionally improved through biotechnology: case studies: executive summary of a task force report by the International Life Sciences Institute, Washington, D.C.
During the last 2 decades, the public and private sectors have made substantial international research progress toward improving the nutritional value of a wide range of food and feed crops. Nevertheless, significant numbers of people still suffer from the effects of undernutrition. In addition, the nutritional quality of feed is often a limiting factor in livestock production systems, particularly those in developing countries. As newly developed crops with nutritionally improved traits come closer to being available to producers and consumers, we must ensure that scientifically sound and efficient processes are used to assess the safety and nutritional quality of these crops. Such processes will facilitate deploying these crops to those world areas with large numbers of people who need them. This document describes 5 case studies of crops with improved nutritional value. These case studies examine the principles and recommendations published by the Intl. Life Sciences Inst. (ILSI) in 2004 for the safety and nutritional assessment of foods and feeds derived from nutritionally improved crops (ILSI 2004). One overarching conclusion that spans all 5 case studies is that the comparative safety assessment process is a valid approach. Such a process has been endorsed by many publications and organizations, including the 2004 ILSI publication. The type and extent of data that are appropriate for a scientifically sound comparative safety assessment are presented on a case-by-case basis in a manner that takes into account scientific results published since the 2004 ILSI report. This report will appear in the January issue of Comprehensive Reviews in Food Science and Food Safety.


Global Bioethics and Culture in a Pluralistic World: How does Culture influence Bioethics in Africa?
Bioethics principles and practice can be influenced by different cultural background. This is because the four globally accepted bioethics principles are often based on basic ethical codes such as autonomy, beneficence, nonmaleficence and justice. Beneficence/nonmaleficence requires us to maximize possible benefits, while minimizing possible harms and consequently secure the well-being of others by refraining from harming them. Autonomy gives individuals the right to self-actualization and decision-making, while justice is concerned with the fair selection and distribution of the burdens and benefits of research among participants. Applications of these principles in cultural settings vary more often from one cultural perspective to the other because of the different understanding and practices of "what is good." The proponents of global ethics may argue that these principles should be universally generalizable and acceptable, but this is not possible because of the existing cultural diversities. In the African set-up, despite the existence of major common cultural practices, there are other norms and practices, which differ from one society to the other within the communities. Therefore, the word "global" bioethics may not be applicable generally in practice except if it can account for the structural dynamics and cultural differences within the complex societies in which we live in. However, the extent to which cultural diversity should be permitted to influence bioethical judgments in Africa, which at present is burdened with many diseases, should be of concern to researchers, ethicist and medical experts taking into considerations the constantly transforming global society. This topic examines the cultural influence on principles and practice of bioethics in Africa.


Optical trapping and optical force positioning of two-dimensional materials.
In recent years, considerable effort has been devoted to the synthesis and characterization of two-dimensional materials. Liquid phase exfoliation (LPE) represents a simple, large-scale method to exfoliate layered materials down to mono- and few-layer flakes. In this context, the contactless trapping, characterization, and manipulation of individual nanosheets hold perspectives for increased accuracy in flake metrology and the assembly of novel functional materials. Here, we use optical forces for high-resolution structural characterization and precise mechanical positioning of nanosheets of hexagonal boron nitride, molybdenum disulfide, and tungsten disulfide obtained by LPE. Weakly optically absorbing nanosheets of boron nitride are trapped in optical tweezers. The analysis of the thermal fluctuations allows a direct measurement of optical forces and the mean flake size in a liquid environment. Measured optical trapping constants are compared with T-matrix light scattering calculations to show a quadratic size scaling for small size, as expected for a bidimensional system. In contrast, strongly absorbing nanosheets of molybdenum disulfide and tungsten disulfide are not stably trapped due to the dominance of radiation pressure over the optical trapping force. Thus, optical forces are used to pattern a substrate by selectively depositing nanosheets in short times (minutes) and without any preparation of the surface. This study will be useful for improving ink-jet printing and for a better engineering of optoelectronic devices based on two-dimensional materials.


Identifying dimensions of fatigue in haemodialysis important to patients, caregivers and health professionals: An international survey.
Patient-reported outcome measures of fatigue used in research in haemodialysis vary widely in the dimensions assessed; and the importance of these dimensions to patients and health professionals is unknown. This study aimed to identify the most important dimensions of fatigue to assess in patients on haemodialysis participating in trials. In an international survey, patients/caregivers and health professionals rated the absolute and relative importance of content and measurement dimensions to include in a core outcome measure of fatigue. A 9-point Likert scale (7-9 indicating critical importance) was used to assess absolute importance and best-worst scale was used to assess importance of each dimension compared to others. In total, 169 patients/caregivers and 336 health professionals from 60 countries completed the survey. Both groups (patients/caregivers and health professionals) rated life participation (7.55), tiredness (7.40), level of energy (7.37), ability to think clearly (7.15), post-dialysis fatigue (7.13), motivation (7.03) and ability to concentrate (7.03) as critically important (mean Likert score greater than 7) content dimensions to include in a core outcome measure. Compared to patients and caregivers, health professionals rated post-dialysis fatigue, memory and verbal abilities more highly. Based on the relative importance scores, life participation was ranked most highly above all content dimensions. Severity was rated and ranked the most important measurement dimension by all stakeholders. A core outcome measure of fatigue should assess impact of fatigue on life participation, tiredness and level of energy, using a severity scale. A consistent and valid measurement of fatigue will improve the value of trials in supporting decision-making based on this important outcome.


Influence of tobacco displays and ads on youth: a virtual store experiment.
To examine the potential impact of banning tobacco displays and ads at the point of sale (POS) on youth outcomes. An interactive virtual convenience store was created with scenarios in which the tobacco product display at the POS was either openly visible (status quo) or enclosed behind a cabinet (display ban), and tobacco ads in the store were either present or absent. A national convenience sample of 1216 youth aged 13 to 17 who were either smokers or nonsmokers susceptible to smoking participated in the study. Youth were randomized to 1 of 6 virtual store conditions and given a shopping task to complete in the virtual store. During the shopping task, we tracked youth's attempts to purchase tobacco products. Subsequently, youth completed a survey that assessed their perceptions about the virtual store and perceptions about the ease of buying cigarettes from the virtual store. Compared with youth in the status quo condition, youth in the display ban condition were less aware that tobacco products were for sale (32.0% vs 85.2%) and significantly less likely to try purchasing tobacco products in the virtual store (odds ratio = 0.30, 95% confidence interval = 0.13-0.67, P < .001). Banning ads had minimal impact on youth's purchase attempts. Policies that ban tobacco product displays at the POS may help reduce youth smoking by deterring youth from purchasing tobacco products at retail stores.


Absolute calibration of a laser system for atmospheric probing.
In order to obtain quantitative data on the backscatter function from laser irradiance backscattered from the atmosphere, the ratio of power transmitted to power received must be accurately known. No absolute measurements of power, optical system transmittance, detector quantum efficiency, or electronic gain are necessarily required. The technique of measuring the power ratio by irradiating a smoked or painted target of known diffuse reflectance at a fixed range is used to calibrate a complete lidar system. The relative area of the output power pulse is monitored by a fast response photodiode, and the relative area of the returned pulse is also recorded after passing through a filter of known high optical density. It is essential to control the temperatures of the laser rod and receiver interference prefilter to ensure proper spectral matching. Field experience gained using this technique is described, and examples of calibration measurements and backscatter functions for smog and cirrus clouds are presented.


Does load-induced ventricular hypertrophy progress to systolic heart failure?
Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.


Day-to-day variability in home blood pressure is associated with cognitive decline: the Ohasama study.
Although an association between high blood pressure and cognitive decline has been reported, no studies have investigated the association between home blood pressure and cognitive decline. Home blood pressure measurements can also provide day-to-day blood pressure variability calculated as the within-participant SD. The objectives of this prospective study were to clarify whether home blood pressure has a stronger predictive power for cognitive decline than conventional blood pressure and to compare the predictive power of the averaged home blood pressure with day-to-day home blood pressure variability for cognitive decline. Of 485 participants (mean age, 63 years) who did not have cognitive decline (defined as Mini-Mental State Examination score, <24) initially, 46 developed cognitive decline after a median follow-up of 7.8 years. Each 1-SD increase in the home systolic blood pressure value showed a significant association with cognitive decline (odds ratio, 1.48; P=0.03). However, conventional systolic blood pressure was not significantly associated with cognitive decline (odds ratio, 1.24; P=0.2). The day-to-day variability in systolic blood pressure was significantly associated with cognitive decline after including home systolic blood pressure in the same model (odds ratio, 1.51; P=0.02), whereas the odds ratio of home systolic blood pressure remained positive, but it was not significant. Home blood pressure measurements can be useful for predicting future cognitive decline because they can provide information not only on blood pressure values but also on day-to-day blood pressure variability.


Personal resources and depression in schizophrenia: The role of self-esteem, resilience and internalized stigma.
Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments.


A Potential Bioelectromagnetic Method to Slow Down the Progression and Prevent the Development of Ultimate Pulmonary Fibrosis by COVID-19.
Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients. Modulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic-often fatal-consequences of the infection. The effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.


Visual sustained attention and numerosity sensitivity correlate with math achievement in children.
In this study, we investigated in school-age children the relationship among mathematical performance, the perception of numerosity (discrimination and mapping to number line), and sustained visual attention. The results (on 68 children between 8 and 11 years of age) show that attention and numerosity perception predict math scores but not reading performance. Even after controlling for several variables, including age, gender, nonverbal IQ, and reading accuracy, attention remained correlated with math skills and numerosity discrimination. These findings support previous reports showing the interrelationship between visual attention and both numerosity perception and math performance. It also suggests that attentional deficits may be implicated in disturbances such as developmental dyscalculia.


A POMDP approach to optimizing P300 speller BCI paradigm.
To achieve high performance in brain-computer interfaces (BCIs) using P300, most of the work has been focused on feature extraction and classification algorithms. Although significant progress has been made in such signal processing methods in the lower layer, the issues in the higher layer, specifically determining the stimulus schedule in order to identify the target reliably and efficiently, remain relatively unexplored. In this paper, we propose a systematic approach to compute an optimal stimulus schedule in P300 BCIs. Our approach adopts the partially observable Markov decision process, which is a model for planning in partially observable stochastic environments. We show that the thus obtained stimulus schedule achieves a significant performance improvement in terms of the success rate, bit rate, and practical bit rate through human subject experiments.


Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes.
Background: Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.Methods: Archival tissue from primary cutaneous melanomas and melanocytic nevi was obtained from four independent institutions and tested with the gene signature. Cases were selected according to pre-defined clinical outcome measures. Malignant lesions were defined as stage I-III primary cutaneous melanomas that produced distant metastases (metastatic to sites other than proximal sentinel lymph node(s)) following diagnosis of the primary lesion. Melanomas that were metastatic at the time of diagnosis, all re-excisions, and lesions with <10% tumor volume were excluded. Benign lesions were defined as cutaneous melanocytic lesions with no adverse long-term events reported.Results: Of 239 submitted samples, 182 met inclusion criteria and produced a valid gene expression result. This included 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. Median time to melanoma metastasis was 18 months. Median follow-up time for nevi was 74.9 months. The gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%.Conclusions: The results of gene expression testing closely correlate with long-term clinical outcomes of patients with melanocytic neoplasms.Impact: Collectively, this provides strong evidence that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma. Cancer Epidemiol Biomarkers Prev; 26(7); 1107-13. ©2017 AACR.


Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis.
The combination of sofosbuvir and velpatasvir is used to treat patients with hepatitis C virus (HCV) infection of different genotypes. We compared the effects of this treatment regimen, with and without ribavirin, on outcomes reported by patients (patient-reported outcomes [PROs]) with HCV infection, with or without cirrhosis. We performed a post hoc analysis of data collected from phase 3 clinical trials (ASTRAL-1, -2, -3, and -4) of 1701 patients infected with HCV of different genotypes treated with sofosbuvir and velpatasvir with ribavirin for 12 weeks (n = 87), sofosbuvir with ribavirin for 12 or 24 weeks (n = 401), and ribavirin-free sofosbuvir and velpatasvir for 12 or 24 weeks (n = 1213). In all trials, participants completed 4 PRO questionnaires (while blinded to their HCV RNA levels): the Short Form-36, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Chronic Liver Disease Questionnaire-HCV Version, and the Work Productivity and Activity Impairment: Specific Health Problem, at multiple time points. We compared baseline PROs and changes in PROs following treatment in patients without cirrhosis (n = 1112), with compensated cirrhosis (n = 338), and with decompensated cirrhosis (n = 251). Baseline PRO scores were as much as 33.5% lower in patients with decompensated cirrhosis than in patients without cirrhosis (P < .05). Following treatment with ribavirin-containing regimens, changes in PRO scores were similar among patients with compensated and decompensated cirrhosis (all P > .01). Treatment with these regimens increased some PRO scores by as much as 11.8% from baseline (P < .05) and reduced others, by as much as 7.1% (P < .05). Despite this, by 12 weeks after cessation of treatment with ribavirin-containing regimens, all PRO decrements resolved; PRO scores increased by as much as 14.2%, and as much as 17.1% at 24 weeks after treatment, regardless of cirrhosis status (all P > .01 between cirrhosis groups). In contrast, treatment with ribavirin-free sofosbuvir and velpatasvir increased PRO scores for patients with compensated cirrhosis, and even more so in patients with decompensated cirrhosis starting at treatment Week 4; no statistically significant decrement was observed at any time point (all 1-sided P values > .05). In multivariate analysis, compensated cirrhosis was associated with a 2.3% to 5.0% greater increase in PRO scores following treatment with sofosbuvir and velpatasvir (P < .05); decompensated cirrhosis was associated with a 5.5%-9.1% greater increase (P < .002). Clinicaltrials.gov number, NCT02201940, NCT02220998, NCT02201953, NCT02201901. In an analysis of data from 4 phase 3 clinical trials, we found that patients with HCV infection (especially those with decompensated cirrhosis) have significant increases in their PRO scores during treatment with sofosbuvir and velpatasvir and after achieving a sustained virologic response.


[Filling phase abnomalities and cystocele].
To evaluate the clinical and urodynamic characteristics of a series of women with lower urinary tract symptoms (bladder filling phase) presenting various rates of cystocele. 119 female patients were included in this study; mean age was 55.8 yr. (range 15-87). All patients underwent urogynecologic physical examination (cystocele was graded 0-3) and complete urodynamic study. Urodynamic terminology and measurements comply with the ICS (InternationaL Continence Society) standards. Statistical significance was established below 0.05. Quantitative variables were compared by the Student's t and non parametric variables by Pearson's chi-square. The most frequently reported symptom was urinary incontinence when coughing (77/118, 65.3%), followed by urge incontinence (71 patients, 60.2%). The grade of cystocele was 0 in 31.1%, 1 in 25.2%, and 2 in 26.1%, and 3 in 17.6%. There was a statistically significant association between grade of cystocele and the symptom "vaginal bulge" (p=0.00002). The presence of cystocele did not show any statistical association with lower urinary tract symptoms of the filling phase. Mean cystomanometric bladder capacity was 224.8 ml. Involuntary contractions of the detrusor muscle appeared in 38 cases (21.9%), stress urinary incontinence in 19 (16%), mixed incontinence in 8 (6.7%) and absence of evidence of urinary incontinence in 58 (48.7%). Patients with urgency had a lower bladder capacity than patients without it (p = 0.02), as did patients with urge incontinence (p = 0.02). Nocturia (p = 0.05), urgency (p = 0.02) and urge incontinence (p = 0.01) were significantly associated to bladder capacity. The existence of involuntary contractions was statistically associated with urge incontinence (p = 0.01). Patients with involuntary contractions during the filling phase showed increased diurnal voiding frequency (p = 0.02), as well as patients without a stress urinary incontinence (p = 0.04) and cases without a stress urinary incontinence (p = 0.04). The symptom incontinence with coughing had a significant statistical association with the urodynamic diagnosis of stress urinary incontinence (p= 0.01). Bladder capacity was augmented in grade 3 cystocele (p = 0.003). The existence of cystocele was not associated with bladder hyperactivity (p = 0.65), neither was the diagnosis of a stress urinary incontinence (p = 0.37). No relationship has been demonstrated between existence and degree of cystocele and functional lower urinary tract symptoms of the filling phase, on the one hand, and urodynamic evidence of bladder hyperactivity and incontinence on the other hand. This could have important therapeutic implications.


Identification of genes affecting alginate biosynthesis in Pseudomonas fluorescens by screening a transposon insertion library.
Polysaccharides often are necessary components of bacterial biofilms and capsules. Production of these biopolymers constitutes a drain on key components in the central carbon metabolism, but so far little is known concerning if and how the cells divide their resources between cell growth and production of exopolysaccharides. Alginate is an industrially important linear polysaccharide synthesized from fructose 6-phosphate by several bacterial species. The aim of this study was to identify genes that are necessary for obtaining a normal level of alginate production in alginate-producing Pseudomonas fluorescens. Polysaccharide biosynthesis is costly, since it utilizes nucleotide sugars and sequesters carbon. Consequently, transcription of the genes necessary for polysaccharide biosynthesis is usually tightly regulated. In this study we used an engineered P. fluorescens SBW25 derivative where all genes encoding the proteins needed for biosynthesis of alginate from fructose 6-phosphate and export of the polymer are expressed from inducible Pm promoters. In this way we would avoid identification of genes merely involved in regulating the expression of the alginate biosynthetic genes. The engineered strain was subjected to random transposon mutagenesis and a library of about 11500 mutants was screened for strains with altered alginate production. Identified inactivated genes were mainly found to encode proteins involved in metabolic pathways related to uptake and utilization of carbon, nitrogen and phosphor sources, biosynthesis of purine and tryptophan and peptidoglycan recycling. The majority of the identified mutants resulted in diminished alginate biosynthesis while cell yield in most cases were less affected. In some cases, however, a higher final cell yield were measured. The data indicate that when the supplies of fructose 6-phosphate or GTP are diminished, less alginate is produced. This should be taken into account when bacterial strains are designed for industrial polysaccharide production.


Function of bright coloration in the wasp spider Argiope bruennichi (Araneae: Araneidae).
There are two major competing explanations for the counter-intuitive presence of bright coloration in certain orb-web spiders. Bright coloration could lure insect prey to the web vicinity, increasing the spider's foraging success. Alternatively, the markings could function as disruptive camouflage, making it difficult for the insect prey to distinguish spiders from background colour variation. We measured the prey capture rates of wasp spiders, Argiope bruennichi, that were blacked out, shielded from view using a leaf fragment, or left naturally coloured. Naturally coloured spiders caught over twice the number of prey as did either blacked-out or leaf-shielded spiders, and almost three times as many orthopteran prey. Spectrophotometer measurements suggest that the bright yellow bands on the spider's abdomen are visible to insect prey, but not the banding on the legs, which could disguise the spider's outline. Thus, our results provide strong support for the hypothesis that bright coloration in the wasp spider acts as a visual lure for insect prey and weak support for the hypothesis that the arrangement of the banding pattern across the spider's body disguises the presence of the spider on the web.


Systematic review of the toxicity of short-course oral corticosteroids in children.
Short-course oral corticosteroids are commonly used in children but are known to be associated with adverse drug reactions (ADRs). This review aimed to identify the most common and serious ADRs and to determine their relative risk levels. A literature search of EMBASE, MEDLINE, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions to identify studies in which oral corticosteroids were administered to patients aged 28 days to 18 years of age for up to and including 14 days of treatment. Each database was searched from their earliest dates to December 2013. All studies providing clear information on ADRs were included. Thirty-eight studies including 22 randomised controlled trials (RCTs) met the inclusion criteria. The studies involved a total of 3200 children in whom 850 ADRs were reported. The three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with respective incidence rates of 5.4%, 4.7% and 4.3% of patients assessed for these ADRs. Infection was one of the most serious ADRs; one child died after contracting varicella zoster. When measured, 144 of 369 patients showed increased blood pressure; 21 of 75 patients showed weight gain; and biochemical hypothalamic-pituitary-adrenal axis suppression was detected in 43 of 53 patients. Vomiting, behavioural changes and sleep disturbance were the most frequent ADRs seen when short-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR. CRD42014008774. By PROSPERO International prospective register of systematic reviews.


Fine needle aspiration biopsy and flow cytometry in the diagnosis of lymphoma.
Fine needle aspiration biopsy (FNAB) is emerging as a technique of potential value in the diagnosis of benign and malignant lesions in areas such as the breast and thyroid gland. Its place in distinguishing reactive from neoplastic lymphoid proliferations, when compared to the established practice of excision biopsy and histopathology, continues to undergo evaluation. Morphology alone discriminates poorly between atypical or lymphoproliferative disorders as seen in the presence of Epstein-Barr or human immunodeficiency virus. Furthermore the polymorphic populations of follicular lymphoma may mimic reactive changes. In addition previous classifications of these tumours using working formulation or Kiel classification relied heavily on architecture, which is a feature not reflected in cytology smears. The World Health Organisation approach includes clinical features, immunophenotyping and cytogenetic profiles to define neoplasms of immunohaematopoietic tissues. Flow cytometry on fine needle aspiration biopsy offers additional advantages in being rapid and objective in quantitatively as well as qualitatively documenting cell surface characteristics. All patients referred for this procedure to Tygerberg Academic Hospital with suspected nodal or extranodal lymphoma between January 2002 and December 2004 were analysed. In each case flow cytometry and cytomorphology were correlated with histopathology on tissue biopsy, bone marrow examination and clinical follow-up for confirmation of diagnosis. Results of the 124 cases were tabulated and statistically processed. Eighty-one met the inclusion criteria, thirteen (16.1%) were not malignant, two (2.5%) were falsely negative, two (2.5%) were equivocal needing histology and in the remaining sixty-four (79%) diagnosis was achieved. Fine needle aspiration coupled with flow cytometry can reliably distinguish between nodal and extranodal neoplastic B-cell population. It is concluded that appropriate use, in a collaborative multidisciplinary setting, may eliminate the need for surgical procedures in many cases. These advances are not widely recognised and this is particularly true in South Africa. Accordingly, such an approach has been prospectively evaluated in the Western Cape showing that the combination of ready availability and diagnostic accuracy, after an initial learning curve, allow accurate characterisation of haematologic malignancies so that excision biopsy may be reserved for specific further studies to provide data not available from this less invasive procedure.


Caring for people with dementia disease (DD) and working in a private not-for-profit residential care facility for people with DD.
Caring for people with dementia and working in dementia care is described as having both rewarding and unpleasant aspects and has been studied to a minor extent. This study aims to explore care providers' narrated experiences of caring for people with dementia disease (DD) and working in a private not-for-profit residential care facility for people with DD. Nine care providers were interviewed about their experiences, the interviews were recorded, transcribed and analysed using thematic analysis. The analysis revealed that participants were struggling to perform person-centred care, which meant trying to see the person behind the disease, dealing with troublesome situations in the daily care, a two-edged interaction with relatives, feelings of shortcomings and troubled conscience, and the need for improvements in dementia care. The analysis also revealed an ambiguous work situation, which meant a challenging value base, the differently judged work environment, feelings of job satisfaction and the need for a functional leadership and management. The results illuminate participants' positive as well as negative experiences and have identified areas requiring improvements. It seems of great importance to strive for a supportive and attendant leadership, a leadership which aims to empower care providers in their difficult work. Using conscience as a driving force together in the work group may benefit care providers' health.


Beating the amorphous limit in thermal conductivity by superlattices design.
The value measured in the amorphous structure with the same chemical composition is often considered as a lower bound for the thermal conductivity of any material: the heat carriers are strongly scattered by disorder, and their lifetimes reach the minimum time scale of thermal vibrations. An appropriate design at the nano-scale, however, may allow one to reduce the thermal conductivity even below the amorphous limit. In the present contribution, using molecular-dynamics simulation and the Green-Kubo formulation, we study systematically the thermal conductivity of layered phononic materials (superlattices), by tuning different parameters that can characterize such structures. We have discovered that the key to reach a lower-than-amorphous thermal conductivity is to block almost completely the propagation of the heat carriers, the superlattice phonons. We demonstrate that a large mass difference in the two intercalated layers, or weakened interactions across the interface between layers result in materials with very low thermal conductivity, below the values of the corresponding amorphous counterparts.


Modeled buoyancy of eggs and larvae of the deep-sea shrimp Aristeus antennatus (Crustacea: Decapoda) in the northwestern Mediterranean Sea.
Information on the buoyancy of eggs and larvae from deep-sea species is rare but necessary for explaining the position of non-swimming larvae in the water column. Due to embryonic morphology and ecology diversities, egg buoyancy has important variations within one species and among other ones. Nevertheless, it has hardly been explored if this buoyancy variability can be a strategy for deep-sea larvae to optimize their transport beyond their spawning areas. In the northwestern Mediterranean Sea, protozoea and mysis larvae of the commercial deep-sea shrimp Aristeus antennatus were recently found in upper layers, but to present, earlier stages like eggs and nauplii have not been collected. Using a Lagrangian transport model and larval characteristics, we evaluate the buoyancy and hydrodynamic effects on the transport of A. antennatus' larvae in the northwestern Mediterranean Sea. The transport models suggested that 75% of buoyant eggs released between 500 and 800 m depth (i.e., known spawning area), reached the upper water layers (0-75 m depth). Then, according to the modeled larval drifts, three spawning regions were defined in the studied area: 1) the northern part, along a continental margin crossed by large submarine canyons; 2) the central part, with two circular circulation structures (i.e., eddies); and 3) the southern part, with currents flowing through a channel. The number of larvae in the most upper layer (0-5 m depth) was higher if the larval transport model accounted for the ascent of eggs and nauplii (81%) instead of eggs reaching the surface before hatching (50%). The larvae reaching the most water upper layer (0-5 m depth) had higher rates of dispersal than the ones transported below the surface layer (deeper than 5 m depth). The results of larval dispersal simulations have implications for the understanding of A. antennatus larval ecology and for management decisions related to the shrimp fisheries in the northwestern Mediterranean Sea.


Transition metal complexes containing the S(NtBu)4(2-) tetraimidosulfate dianion.
Three novel metal complexes [(acac)2Cu2(NtBu)4S] (), [Li(thf)4]2[I4Cd2(NtBu)4S] () and [(thf)2Li{(SiMe3)2N}Zn(NtBu)4S] () are prepared from the intended transmetalation of the dilithium complex of N,N',N'',N'''-tetrakis(tert-butyl)tetraimidosulfate [(thf)4Li2(NtBu)4S] (). The two lithium cations are replaced by either the cationic (acac)Cu(ii) moiety, the neutral I2Cd(ii) residue or only a single lithium cation is substituted by the cationic (Me3Si)2NZn(ii) fragment. The complexes show two main results: first the S(NtBu)4(2-) tetrahedron can serve as a ligand to transition metals from the soft Cu(ii) to the harder Zn(ii) at opposite sides and second the S-N bond distances vary only marginally in response to the various metals and the four distances constantly sum up to 6.38(2) Å. Hence the electropositive sulfur atom responds by internal shift to the metal-polarized negative charge at the outside of the S(NR)4(2-) tetrahedron.


Steroidogenesis in rabbit preimplantation embryos.
Rabbit preimplantation embryos were flushed from the reproductive tract at 24 hr (1- to 2-cell stage), 48 hr (morula), 72 hr (morula), 96 hr (blastocyst), 120 hr (blastocyst), and 144 hr (blastocyst) post coitum. At 168 hr (early postimplantation period), gestation sacs were excised, frozen, and sectioned in a cryostat. Delta5-3beta-Hydroxysteroid dehydrogenase [3(or 17)beta-hydroxysteroid:NAD(P) oxidoreductase, EC 126.96.36.199] activity was determined histochemically in whole preimplantation embryos and in sectioned postimplantation embryos. 3beta-Hydroxysteroid dehydrogenase activity began at 48 hr and was sustained through the late blastocyst stage (144 hr), with the exception of a brief drop, possibly cessation, of activity at 72 hr. There was no activity at 168 hr. Since 3 beta-hydroxysteroid dehydrogenase is a key enzyme in the metabolism of steroid hormones, its presence is strong evidence for steroidogenesis. Only 144-hr preimplantation embryos were used to determine 17 beta-hydroxysteroid dehydrogenase (estradiol-17beta:NAD 17-oxidoreductase, EC 220.127.116.11) activity, which was present, suggesting synthesis of estrogen. By means of radioimmunoassay, 144-hr preimplantation embryos were found to contain estradiol-17beta. Other authors have shown that rabbit blastocysts contain progesterone and other steroids, and these embryos can synthesize steroids from non-steroid and steroid precursors. Therefore, our results plus those of others prove that rabbit preimplantation embryos synthesize steroid hormones. Our present and previous results (with rats, hamsters, and mice) suggest that the steroid hormones synthesized by the embryo are critical for preimplantation embryogenesis and for implantation of the lbastocyst.


Observing the onset of disability in older adults.
One of the greatest threats to the ability of older adults to live independently is the onset of disability in activities adults perform in their daily lives, such as dressing, eating, toileting, managing one's money, preparing meals and so on. This article examines the onset of disability in older adult Americans using three waves of the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey (1993, 1995, 1998; n=4228). We use medical/demographic factors (arthritis, heart disease, diabetes; age, gender, race/ethnicity, wealth), baseline characteristics (affect, cognition, health behaviors, medical insurance), and time-varying covariates (changes in chronic conditions and baseline characteristics) to predict the onset of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) disability, individually and in the aggregate, over time. We find the onset of ADL and IADL disability is a complex process, suggesting important roles for medical, demographic, social, psychological, and behavioral triggers, specifically negative affect, higher body weight, and by the lack of vigorous exercise. We also find that individual ADL and IADL impairments are predicted by a variety of different factors, suggesting that summary measures of disability may be masking a wealth of potentially useful interventions. In general, public health efforts in the area of controlling obesity and treating depressive symptoms should be supported.


Experimental quantum teleportation over a high-loss free-space channel.
We present a high-fidelity quantum teleportation experiment over a high-loss free-space channel between two laboratories. We teleported six states of three mutually unbiased bases and obtained an average state fidelity of 0.82(1), well beyond the classical limit of 2/3. With the obtained data, we tomographically reconstructed the process matrices of quantum teleportation. The free-space channel attenuation of 31 dB corresponds to the estimated attenuation regime for a down-link from a low-earth-orbit satellite to a ground station. We also discussed various important technical issues for future experiments, including the dark counts of single-photon detectors, coincidence-window width etc. Our experiment tested the limit of performing quantum teleportation with state-of-the-art resources. It is an important step towards future satellite-based quantum teleportation and paves the way for establishing a worldwide quantum communication network.


[Effects of Health Qigong Baduanjin on diabetes related indexes in middle-aged obese women].
To investigate the effect of Health Qigong Baduanjin on the related indexes of obese middle aged women with diabetes and to provide new ideas for the intervention treatment of diabetes. A total of 40 middle-aged female obese diabetic patients were randomly divided into the control group and the exercise group(n=20), the age was(57.2±5.4) years old. Fitness training group performed eight new Baduanjin exercises for 24 weeks of intervention, the control group did not exercise, body weight, waist circumference, body mass index (BMI), waist hip ratio (WHR), fasting blood glucose (FPG), glycosylated hemoglobin (HbAlc), triglyceride(TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) levels and serum retinol binding protein 4(RBP4) index were observed in the two groups. After exercise, the waist, WHR, FPG, TG, HbAlc, HDL and RBP4 levels of the the patients in the experimental group were decreased significantly compared with those of before exercise and those of the patients in the experimental control group before and after exercise (P<0.05). Health Qigong Baduanjin can reduce the blood sugar of obese female patients with diabetes, and has some improvement effect on the body part of obesity and blood lipid indicators.


Symptoms and delay times during myocardial infarction in 694 patients with and without diabetes; an explorative cross-sectional study.
In myocardial infarction (MI) a short pre-hospital delay, prompt diagnosis and timely reperfusion treatment can improve the prognosis. Despite the importance of timely care seeking, many patients with MI symptoms delay seeking medical care. Previous research is inconclusive about differences in symptom presentation and pre-hospital delay between patients with and without diabetes during MI. The aim of this study was to describe symptoms and patient delay during MI in patients with and without diabetes. Swedish cross-sectional multicentre survey study enrolling MI patients in 5 centres within 24 h from admittance. Chest pain was common in patients both with and without diabetes and did not differ after adjustment for age and sex. Patients with diabetes had higher risk for shoulder pain/discomfort, shortness of breath, and tiredness, but lower risk for cold sweat. The three most common symptoms reported by patients with diabetes were chest pain, pain in arms/hands and tiredness. In patients without diabetes the most common symptoms were chest pain, cold sweat and pain in arms/hands. Median patient delay time was 2 h, 24 min for patients with diabetes and 1 h, 15 min for patients without diabetes (p = 0.024). Chest pain was common both in patients with and without diabetes. There were more similarities than differences in MI symptoms between patients with and without diabetes but patients with diabetes had considerably longer delay. This knowledge is important not only for health care personnel meeting patients with suspected MI, but also for the education of people with diabetes.


Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.
Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.


Differential expression of melanopsin isoforms Opn4L and Opn4S during postnatal development of the mouse retina.
Photosensitive retinal ganglion cells (pRGCs) respond to light from birth and represent the earliest known light detection system to develop in the mouse retina. A number of morphologically and functionally distinct subtypes of pRGCs have been described in the adult retina, and have been linked to different physiological roles. We have previously identified two distinct isoforms of mouse melanopsin, Opn4L and Opn4S, which are generated by alternate splicing of the Opn4 locus. These isoforms are differentially expressed in pRGC subtypes of the adult mouse retina, with both Opn4L and Opn4S detected in M1 type pRGCs, and only Opn4L detected in M2 type pRGCs. Here we investigate the developmental expression of Opn4L and Opn4S and show a differential profile of expression during postnatal development. Opn4S mRNA is detected at relatively constant levels throughout postnatal development, with levels of Opn4S protein showing a marked increase between P0 and P3, and then increasing progressively over time until adult levels are reached by P10. By contrast, levels of Opn4L mRNA and protein are low at birth and show a marked increase at P14 and P30 compared to earlier time points. We suggest that these differing profiles of expression are associated with the functional maturation of M1 and M2 subtypes of pRGCs. Based upon our data, Opn4S expressing M1 type pRGCs mature first and are the dominant pRGC subtype in the neonate retina, whereas increased expression of Opn4L and the maturation of M2 type pRGCs occurs later, between P10 and P14, at a similar time to the maturation of rod and cone photoreceptors. We suggest that the distinct functions associated with these cell types will develop at different times during postnatal development.


Changes in human skeletal muscle contractile function following stimulated eccentric exercise.
Indices of human skeletal muscle contractile function were examined in nine subjects for up to 9 days following a single bout of stimulated eccentric exercise. Eccentric muscle actions of the knee extensor muscles were evoked by percutaneous electrical myostimulation (PES). Delayed onset muscle soreness (DOMS), elevated serum creatine kinase activity, chronic force loss, and a decline in the 20:100 Hz force ratio were observed in the days postexercise. The exercised knee extensor muscles demonstrated an impaired ability to respond to PES. This was evident by an increased time delay between the start of 100 Hz PES and the onset of contraction immediately postexercise [22.3 (SD 15.9)%, P < 0.01] and 3 days postexercise [14.9 (SD 18.1)%, P < 0.05]. Muscle relaxation rates appeared unaffected by the eccentric exercise protocol, where the muscles showed no differences in the time between the end of PES and the onset of relaxation (P > 0.05). During the days following the exercise, no significant differences were observed in the time between the start of contraction and attainment of 70% of the mean tetanic force following a single 1-s pulse of PES. Similarly, no significant differences were observed in the time between the start of relaxation and attainment of 70% of the total relaxation during the same time. The increased delay in excitation-contraction coupling observed immediately postexercise and 3 days after the exercise, may reflect a damage-induced delay in action potential propagation. Muscle relaxation rates postexercise remained unchanged, which would seem to indicate normal functioning of the sarcoplasmic reticulum, suggesting this was not the site of failure in excitation-contraction coupling.


Soy, red clover, and isoflavones and breast cancer: a systematic review.
Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer. Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects. Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥ 100 mg) isoflavones can be recommended for breast cancer patients.


Massive exacerbation of multiple sclerosis after withdrawal and early restart of treatment with natalizumab.
We present a 46-year-old woman with a relapse of multiple sclerosis (MS) that began 3 months after withdrawal from long-term treatment with natalizumab. Shortly after restart of a single dose of natalizumab she developed a fulminant MS rebound with stupor and tetraparesis. Cerebral MRI showed massive progression in the number of lesions and tumefactive lesions with ring gadolinium-enhancement. Stereotactic brain biopsy revealed acute demyelination and B-cell dominated inflammation. The patient improved during therapeutic plasma exchange. We speculate that early restart of natalizumab in the case of a relapse may worsen disease evolution possibly by modifying regulatory immune effector processes during an inflammatory rebound phase. A restart of natalizumab in MS patients suffering from a recent relapse or with signs of active inflammation should be considered with caution.


Selective suppression of CARS signal with three-beam competing stimulated Raman scattering processes.
Coherent Raman scattering spectroscopy and microscopy are useful methods for studying the chemical and biological structures of molecules with Raman-active modes. In particular, coherent anti-Stokes Raman scattering (CARS) microscopy, which is a label-free method capable of imaging structures by displaying the vibrational contrast of the molecules, has been widely used. However, the lack of a technique for switching-off the CARS signal has prevented the development of the super-resolution Raman imaging method. Here, we demonstrate that a selective suppression of the CARS signal is possible by using a three-beam double stimulated Raman scattering (SRS) scheme; the three beams are the pump, Stokes, and depletion lights in order of frequency. Both pump-Stokes and pump-depletion beam pairs can generate SRS processes by tuning their beat frequencies to match two different vibrational modes, then two CARS signals induced by pump-Stokes-pump and pump-depletion-pump interactions can be generated, where the two CARS signals are coupled with each other because they both involve interactions with the common pump beam. Herein, we show that as the intensity of the depletion beam is increased, one can selectively suppress the pump-Stokes-pump CARS signal because the pump-depletion SRS depletes the pump photons. A detailed theoretical description of the coupled differential equations for the three incident fields and the generated CARS signal fields is presented. Taking benzene as a molecular system, we obtained a maximum CARS suppression efficiency of about 97% with our experimental scheme, where the ring breathing mode of the benzene is associated with pump-Stokes-pump CARS, while the C-H stretching mode is associated with the competing pump-depletion SRS process. We anticipate that this selective switching-off scheme will be of use in developing super-resolution label-free CARS microscopy.


Microfluidic devices for modeling cell-cell and particle-cell interactions in the microvasculature.
Cell-fluid and cell-cell interactions are critical components of many physiological and pathological conditions in the microvasculature. Similarly, particle-cell interactions play an important role in targeted delivery of therapeutics to tissue. Development of in vitro fluidic devices to mimic these microcirculatory processes has been a critical step forward in our understanding of the inflammatory process, developing of nano-particulate drug carriers, and developing realistic in vitro models of the microvasculature and its surrounding tissue. However, widely used parallel plate flow based devices and assays have a number of important limitations for studying the physiological conditions in vivo. In addition, these devices are resource hungry and time consuming for performing various assays. Recently developed, more realistic, microfluidic based devices have been able to overcome many of these limitations. In this review, an overview of the fluidic devices and their use in studying the effects of shear forces on cell-cell and cell-particle interactions is presented. In addition, use of mathematical models and computational fluid dynamics (CFD) based models for interpreting the complex flow patterns in the microvasculature is highlighted. Finally, the potential of 3D microfluidic devices and imaging for better representing in vivo conditions under which cell-cell and cell-particle interactions take place is discussed.


Abnormal features of Macoma balthica (Bivalvia) in the Baltic Sea: alerting symptoms of environmental adversity?
Recent studies of the Baltic clam Macoma balthica (L.) from the southern Baltic (the Gulf of Gdansk) have revealed striking morphological, histological and cytogenetic features. Strong deformation of the shell, including elongation of the posterior end and the appearance of an easily visible flexure in this part, has been recorded. The population contribution of the deformed blunt shelled ("irregular") clams ranged from 0% to 65% and tended to increase with depth. The morphologically "irregular" clams had higher accumulated tissue concentrations of trace metals (As, Ag, Cd, Pb, Cu and Zn), indicating a different metal handling ability. Adverse conditions in deeper water regions of the Gulf (e.g. hypoxia, hydrogen sulphide, elevated bioavailability of contaminants) have been suggested as inducers of the phenotypical changes (morphological deformation) in part of the population and, in parallel, of the specific physiological adaptations that result in higher metal accumulation in the "irregular" clams. Cytogenetic and histological analyses showed the presence of tumours in gill cells and digestive system of the affected clams, the prevalence of disseminated neoplasia ranging from 0% to 94% depending on the site. The disease was manifested by a modified karyotype (i.e. an abnormal number and morphology of chromosomes), a higher activity of nucleolar organizer regions (AgNORs), and tissue lesions (enlarged cells, actively proliferative with pleomorphic nuclei). Bottom sediments showed acute toxicity and have been proposed as a source of an initialising carcinogenic factor. However, none of the ecotoxicological studies provided was successful in the clear demonstration of a single (or multifactorial) agent that can account for the disseminated neoplasia.


Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.
We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.


The flux dynamics behavior of the two competing high temperature superconducting phases in underdoped LaCuO4.06.
In complex transition metal oxides (TMO) an arrested electronic phase separation (PS) appears by tuning the system near a Lifshitz transition in multiband Hubbard models. The PS in La2CuO4+y near insulator to metal transition (IMT) is made of short range Charge Density Wave (CDW) order inhomogeneity coexisting with quenched lattice disorder. While at high doping y = 0.1 percolation gives a single superconducting phase, near the IMT at y = 0.06 two coexisting superconducting phases appear: the first one with a critical temperature Tc1 = 16 K and the second one with Tc2 = 29 K. It is known that the two superconducting phases are characterized by two different space geometry because of two different spatial distributions of both CDW order and dopants self-organization. Here we show that these two phases show different flux dynamic regimes using alternating current (AC) multi-harmonic susceptibility experiments. This is a unique technique capable to investigate multi-phase superconductors and characterize their transport properties in a percolative scenario. Results point out that the low critical temperature phase is well described by a bulk-like flux pinning with a 2D geometry while the phase with higher critical temperature shows a 'barrier pinning' mechanism providing direct evidence of two different superconducting vortex dynamics in different complex geometrical spaces.


Whole genome phylogenetic investigation of a West Nile virus strain isolated from a tick sampled from livestock in north eastern Kenya.
West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions. A total of 10,488 ticks were sampled from animal hosts, classified to species and processed in pools of up to eight ticks per pool. Virus screening was performed by cell culture, RT-PCR and sequencing. Phylogenetic analysis was carried out to determine the evolutionary relationships of our isolate. Among other viruses, WNV was isolated from a pool of Rhipicephalus pulchellus sampled from cattle, sequenced and submitted to GenBank (Accession number: KC243146). Comparative analysis with 27 different strains revealed that our isolate belongs to lineage 1 and clustered relatively closely to isolates from North Africa and Europe, Russia and the United States. Overall, Bayesian analysis based on nucleotide sequences showed that lineage 1 strains including the Kenyan strain had diverged 200 years ago from lineage 2 strains of southern Africa. Ijara strain collected from a tick sampled on livestock was closest to another Kenyan strain and had diverged 20 years ago from strains detected in Morocco and Europe and 30 years ago from strains identified in the USA. To our knowledge, this is the first characterized WNV strain isolated from R. pulchellus. The epidemiological role of this tick in WNV transmission and dissemination remains equivocal but presents tick verses mosquito virus transmission has been neglected. Genetic data of this strain suggest that lineage 1 strains from Africa could be dispersed through tick vectors by wild migratory birds to Europe and beyond.


Nanocardboard as a nanoscale analog of hollow sandwich plates.
Corrugated paper cardboard provides an everyday example of a lightweight, yet rigid, sandwich structure. Here we present nanocardboard, a monolithic plate mechanical metamaterial composed of nanometer-thickness (25-400 nm) face sheets that are connected by micrometer-height tubular webbing. We fabricate nanocardboard plates of up to 1 centimeter-square size, which exhibit an enhanced bending stiffness at ultralow mass of ~1 g m-2. The nanoscale thickness allows the plates to completely recover their shape after sharp bending even when the radius of curvature is comparable to the plate height. Optimally chosen geometry enhances the bending stiffness and spring constant by more than four orders of magnitude in comparison to solid plates with the same mass, far exceeding the enhancement factors previously demonstrated at both the macroscale and nanoscale. Nanocardboard may find applications as a structural component for wings of microflyers or interstellar lightsails, scanning probe cantilevers, and other microscopic and macroscopic systems.


Allergenicity assessment of Allium sativum leaf agglutinin, a potential candidate protein for developing sap sucking insect resistant food crops.
Mannose-binding Allium sativum leaf agglutinin (ASAL) is highly antinutritional and toxic to various phloem-feeding hemipteran insects. ASAL has been expressed in a number of agriculturally important crops to develop resistance against those insects. Awareness of the safety aspect of ASAL is absolutely essential for developing ASAL transgenic plants. Following the guidelines framed by the Food and Agriculture Organization/World Health Organization, the source of the gene, its sequence homology with potent allergens, clinical tests on mammalian systems, and the pepsin resistance and thermostability of the protein were considered to address the issue. No significant homology to the ASAL sequence was detected when compared to known allergenic proteins. The ELISA of blood sera collected from known allergy patients also failed to show significant evidence of cross-reactivity. In vitro and in vivo assays both indicated the digestibility of ASAL in the presence of pepsin in a minimum time period. With these experiments, we concluded that ASAL does not possess any apparent features of an allergen. This is the first report regarding the monitoring of the allergenicity of any mannose-binding monocot lectin having insecticidal efficacy against hemipteran insects.


Disentangling the potential effects of land-use and climate change on stream conditions.
Land-use and climate change are significantly affecting stream ecosystems, yet understanding of their long-term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land-use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin-wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land-use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project - Phase 5 (CMIP5) and a watershed-wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land-use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed-wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land-use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed-wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%-26.2% of stream kilometers, dependent on land-use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land-use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions.


Does D3 surgery offer a better survival outcome compared to D1 surgery for gastric cancer? A result based on a hospital population of two decades as taking D2 surgery for reference.
We conducted a retrospective study in our hospital in which we compared D1 with D3 through D2 lymphadenectomy for gastric cancer in terms of morbidity, postoperative mortality, long-term survival after surgery. 567 patients who were performed curative intent between 1980 and 2003 were enrolled. 187 in the D1 group, 189 in the D2 group and 191 in the D3 group. Every procedure was verified by pathological analyses. The primary endpoints were 5-year overall survival. Median follow-up periods were 36 months and 60 months for D1 group and D3 group. Overall 5-year survival rate was significantly higher in patients underwent D3 surgery than in those performed D1 surgery (37.4% vs 48.7%; log-rank, p = 0.027). For the cases followed up to 120 months, the 10-year overall survival rate was 29% (95% CI, 22.1% to 35.9%) for the D1 group and 33.7% (95% CI, 26.6% to 40.8%) for the D3 group (log-rank, p = 0.005). D1 surgery should be operated only for patients with Borrmann I disease. As D3 gastrectomy is associated with low mortality and adequate survival times when performed in selected institutions that have had sufficient experience with the operation and with postoperative management, we recommend D3 lymphadenectomy for patients with curable gastric cancer.


Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization.
The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter. In particular, when co-expressed with inducible Cre-ERT2, our system enables parallel, independent manipulation of alleles targeted by Cas9 and traditional recombinase with single-cell specificity. We anticipate this platform will be used for the systematic characterization and identification of essential genes, as well as the investigation of the interactions between functional genes.


The reliability of the Vestibular Autorotation Test (VAT) in patients with dizziness.
To establish intrarater and interrater reliability of the Vestibular Autorotation Test (VAT) (Western Systems Research Inc., Pasadena, CA) in a clinical sample of individuals reporting dizziness. Ninety-eight patients with reports of dizziness referred for vestibular function testing performed repeated trials of horizontal VAT. A subsample of 49 individuals repeated the test for a second rater. Approximately 66% of subjects were unable to meet the performance criterion of six consecutive trials where data was displayed at frequencies > or =3.9 Hz with coherence values held constant trial to trial. There was a good level of intrarater reliability for gain independent of the effects of practice (intraclass correlation coefficient [ICC] = 0.78 [95% confidence interval [CI]: 0.69-0.87] to 0.95 [(95% CI: 0.93-0.97]). A significant difference in intrarater reliability was found when the first three trials were compared to the last three trials for phase (ICC ranged from 0.04 [95% CI: 0.00-0.31] to 0.96 [95% CI: 0.93-0.97]) and asymmetry (ICC ranged from 0.39 [95% CI: 0.17-0.56] to 0.73 [95% CI: 0.32-0.81]) particularly at frequencies > or =4.3 Hz. Interrater reliability was good to excellent across all variables at frequencies < or =3.9 Hz. Many patients had difficulty performing the VAT. The reliability estimates for phase and asymmetry, but not gain, were significantly affected by practice. Careful attention to patient preparation, instruction, and test monitoring including sufficient patient practice before data collection are likely to be critical factors to ensure quality data.


Decision strategies of hearing-impaired listeners in spectral shape discrimination.
The ability to discriminate between sounds with different spectral shapes was evaluated for normal-hearing and hearing-impaired listeners. Listeners detected a 920-Hz tone added in phase to a single component of a standard consisting of the sum of five tones spaced equally on a logarithmic frequency scale ranging from 200 to 4200 Hz. An overall level randomization of 10 dB was either present or absent. In one subset of conditions, the no-perturbation conditions, the standard stimulus was the sum of equal-amplitude tones. In the perturbation conditions, the amplitudes of the components within a stimulus were randomly altered on every presentation. For both perturbation and no-perturbation conditions, thresholds for the detection of the 920-Hz tone were measured to compare sensitivity to changes in spectral shape between normal-hearing and hearing-impaired listeners. To assess whether hearing-impaired listeners relied on different regions of the spectrum to discriminate between sounds, spectral weights were estimated from the perturbed standards by correlating the listener's responses with the level differences per component across two intervals of a two-alternative forced-choice task. Results showed that hearing-impaired and normal-hearing listeners had similar sensitivity to changes in spectral shape. On average, across-frequency correlation functions also were similar for both groups of listeners, suggesting that as long as all components are audible and well separated in frequency, hearing-impaired listeners can use information across frequency as well as normal-hearing listeners. Analysis of the individual data revealed, however, that normal-hearing listeners may be better able to adopt optimal weighting schemes. This conclusion is only tentative, as differences in internal noise may need to be considered to interpret the results obtained from weighting studies between normal-hearing and hearing-impaired listeners.


A prospective study of the effects of ultralow volume (ULV) aerial application of malathion on epidemic Plasmodium falciparum malaria. IV. Epidemiologic aspects.
In the Miragoane Valley of Haiti a consistent pattern in the incidence of Plasmodium falciparum malaria over a 10-year period made it possible to predict an annual outbreak and perform a prospective study to test the effects of aerial ultralow volume (ULV) malathion on epidemic levels of this disease. At the end of October 1972, after epidemic levels (100 cases/month/10,000 population) had been reached, spray operations were begun. The first spray cycle produced a sharp and immediate drop in populations of the vector Anopheles albimanus, followed 4 weeks later by a decrease in the incidence of malaria throughout the valley. Although the incidence of malaria was similar in sprayed and unsprayed areas prior to the effect of ULV malathion (176.1 and 198.7 cases/month/10,000 population, respectively), it was significantly different during the subsequent 3 months (16.8 cases/month/10,000 population in sprayed areas and 65.4 in unsprayed; p less than 0.001). Travel histories indicated that only 4% of all cases had spent a night away from home during the 4 weeks prior to onset of symptoms; therefore, we concluded that these incidence data represent malaria transmission in the valley. Results of the study indicate that aerial spraying of ULV malathion can interrupt epidemic transmission of P. falciparum malaria by a susceptible vector.


Cerebellum and cognition in multiple sclerosis: the fall status matters.
Cerebellar volume has been linked with cognitive performances in MS; however, the association in terms of fall status has never been compared. Therefore, the objective of the current study was to compare cognitive performance with cerebellar volume between MS fallers and non-fallers. The cross-sectional study included 140 PwMS (96 women). MRI volumetric analysis was based on the FreeSurfer image analysis suite. Volumes of the cerebellar gray and white matter were identified as the region of interest. Cognitive function included scores obtained from a computerized cognitive battery of tests. The sample was divided into fallers and non-fallers. MS fallers demonstrated a lower global cognitive performance and reduced gray and white matter cerebellar volumes compared to non-fallers. A significant association was found between total gray and white matter cerebellar volume and visual spatial subdomain (P value = 0.044 and 0.032, respectively) in the non-fallers group. The association remained significant after controlling for the total cranial volume and neurological disability (P value = 0.026 and 0.047, respectively). A relationship was found between the visual spatial score and the left gray matter cerebellum volume; R2 = 0.44, P value = 0.021. We believe that a unique relationship exists between the cerebellum structure and cognitive processing according to fall history in PwMS and should be considered when investigating the association between brain functioning and cognitive performances in MS.


No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.
The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.