Non-random DNA fragmentation in next-generation sequencing.
Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed "reads" are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions.


Elevated cranial ultrasound resistive indices are associated with improved neurodevelopmental outcomes one year after pediatric cardiac surgery: A single center pilot study.
To determine if a non-invasive, repeatable test can be used to predict neurodevelopmental outcomes in patients with congenital heart disease. This was a prospective study of pediatric patients less than two months of age undergoing congenital heart surgery at the Children's Health Children's Medical Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized during the surgery, and ultrasound (US) resistive indices (RI) of the major cranial vessels were obtained prior to surgery, immediately post-operatively, and prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to z transformation were used where appropriate. A total of 16 patients were enrolled. All had US data. Of the sixteen patients, two died prior to the neurodevelopmental testing, six did not return for the neurodevelopmental testing, and eight patients completed the neurodevelopmental testing. There were no significant correlations between the prior to surgery and prior to discharge US RI and neurodevelopmental outcomes. The immediate post-operative US RI demonstrated a strong positive correlation with standardized neurodevelopmental outcome measures. We were able to demonstrate qualitative differences using multichannel NIRS during surgery, but experienced significant technical difficulties implementing consistent monitoring. A higher resistive index in the major cerebral blood vessels following cardiac surgery in the neonatal period is associated with improved neurological outcomes one year after surgery. Obtaining an ultrasound with resistive indices of the major cerebral vessels prior to and after surgery may yield information that is predictive of neurodevelopmental outcomes.


Neuroinflammation and white matter pathology in schizophrenia: systematic review.
Neuroinflammation and white matter pathology have each been independently associated with schizophrenia, and experimental studies have revealed mechanisms by which the two can interact in vitro, but whether these abnormalities simultaneously co-occur in people with schizophrenia remains unclear. We searched MEDLINE, EMBASE, PsycINFO and Web of Science from inception through 12 January 2014 for studies reporting human data on the relationship between microglial or astroglial activation, or cytokines and white matter pathology in schizophrenia. Fifteen studies totaling 792 subjects (350 with schizophrenia, 346 controls, 49 with bipolar disorder, 37 with major depressive disorder and 10 with Alzheimer's disease) met all eligibility criteria. Five neuropathological and two neuroimaging studies collectively yielded consistent evidence of an association between schizophrenia and microglial activation, particularly in white rather than gray matter regions. Ultrastructural analysis revealed activated microglia near dystrophic and apoptotic oligodendroglia, demyelinating and dysmyelinating axons and swollen and vacuolated astroglia in subjects with schizophrenia but not controls. Two neuroimaging studies found an association between carrier status for a functional single nucleotide polymorphism in the interleukin-1β gene and abnormal white as well as gray matter volumes in schizophrenia but not controls. A neuropathological study found that orbitofrontal white matter neuronal density was increased in schizophrenia cases exhibiting high transcription levels of pro-inflammatory cytokines relative to those exhibiting low transcription levels and to controls. Schizophrenia was associated with decreased astroglial density specifically in subgenual cingulate white matter and anterior corpus callosum, but not other gray or white matter areas. Astrogliosis was consistently absent. Data on astroglial gene expression, mRNA expression and protein concentration were inconsistent. Neuroinflammation is associated with white matter pathology in people with schizophrenia, and may contribute to structural and functional disconnectivity, even at the first episode of psychosis.


Molecular profiles of parvalbumin-immunoreactive neurons in the superior temporal cortex in schizophrenia.
Dysregulation of pyramidal cell network function by the soma- and axon-targeting inhibitory neurons that contain the calcium-binding protein parvalbumin (PV) represents a core pathophysiological feature of schizophrenia. In order to gain insight into the molecular basis of their functional impairment, we used laser capture microdissection (LCM) to isolate PV-immunolabeled neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem schizophrenia and normal control brains. We then extracted ribonucleic acid (RNA) from these neurons and determined their messenger RNA (mRNA) expression profile using the Affymetrix platform of microarray technology. Seven hundred thirty-nine mRNA transcripts were found to be differentially expressed in PV neurons in subjects with schizophrenia, including genes associated with WNT (wingless-type), NOTCH, and PGE2 (prostaglandin E2) signaling, in addition to genes that regulate cell cycle and apoptosis. Of these 739 genes, only 89 (12%) were also differentially expressed in pyramidal neurons, as described in the accompanying paper, suggesting that the molecular pathophysiology of schizophrenia appears to be predominantly neuronal type specific. In addition, we identified 15 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of the predicted targets of these miRNAs included the signaling pathways found by microarray to be dysregulated in schizophrenia. Taken together, findings of this study provide a neurobiological framework within which hypotheses of the molecular mechanisms that underlie the dysfunction of PV neurons in schizophrenia can be generated and experimentally explored and, as such, may ultimately inform the conceptualization of rational targeted molecular intervention for this debilitating disorder.


Frozen steady states in active systems.
Even simple active systems can show a plethora of intriguing phenomena and often we find complexity where we would have expected simplicity. One striking example is the occurrence of a quiescent or absorbing state with frozen fluctuations that at first sight seems to be impossible for active matter driven by the incessant input of energy. While such states were reported for externally driven systems through macroscopic shear or agitation, the investigation of frozen active states in inherently active systems like cytoskeletal suspensions or active gels is still at large. Using high-density motility assay experiments, we demonstrate that frozen steady states can arise in active systems if active transport is coupled to growth processes. The experiments are complemented by agent-based simulations which identify the coupling between self-organization, growth, and mechanical properties to be responsible for the pattern formation process.


Diaporthe diversity and pathogenicity revealed from a broad survey of grapevine diseases in Europe.
Species of Diaporthe are considered important plant pathogens, saprobes, and endophytes on a wide range of plant hosts. Several species are well-known on grapevines, either as agents of pre- or post-harvest infections, including Phomopsis cane and leaf spot, cane bleaching, swelling arm and trunk cankers. In this study we explore the occurrence, diversity and pathogenicity of Diaporthe spp. associated with Vitis vinifera in major grape production areas of Europe and Israel, focusing on nurseries and vineyards. Surveys were conducted in Croatia, Czech Republic, France, Hungary, Israel, Italy, Spain and the UK. A total of 175 Diaporthe strains were isolated from asymptomatic and symptomatic shoots, branches and trunks. A multi-locus phylogeny was established based on five genomic loci (ITS, tef1, cal, his3 and tub2), and the morphological characters of the isolates were determined. Preliminary pathogenicity tests were performed on green grapevine shoots with representative isolates. The most commonly isolated species were D. eres and D. ampelina. Four new Diaporthe species described here as D. bohemiae, D. celeris, D. hispaniae and D. hungariae were found associated with affected vines. Pathogenicity tests revealed D. baccae, D. celeris, D. hispaniae and D. hungariae as pathogens of grapevines. No symptoms were caused by D. bohemiae. This study represents the first report of D. ambigua and D. baccae on grapevines in Europe. The present study improves our understanding of the species associated with several disease symptoms on V. vinifera plants, and provides useful information for effective disease management.


Dietitians and exercise physiologists in primary care: lifestyle interventions for patients with depression and/or anxiety.
Mental illness affects one in five Australians in any given year and depression, anxiety and substance abuse are the most prevalent of the mental health problems. Mental illness is traditionally managed with medication and psychological intervention but exercise and diet have also been shown to be related to mental illness and are associated with improvements in mental health. The present article aims to describe the background and practical issues arising from the establishment of diet and exercise assessments and intervention for people receiving treatment for depression and anxiety in general practice settings. Patients were referred by their general practitioners, and attended sessions either in rooms at their practitioner's surgery or at a central clinic location. The program involved an initial assessment, four individual consultations with a dually qualified dietitian and exercise physiologist, and a final assessment. Issues in the process of assessing mental health, diet quality, physical fitness and physical activity behaviours are described as are key components of the tailored treatment programs. Strategies for improving motivation and adherence such as adjusting frequency of sessions, use of homework and means of communication are highlighted.


Magnesium in tap and bottled mineral water in Spain and its contribution to nutritional recommendations.
An appropriate magnesium intake has proved to have beneficial effects on bone health, reduce insulin resistance and prevent atherosclerosis. To determine the concentration of magnesium in drinking water and bottled mineral water in Spain and assess its daily contribution to dietary recommendations. We used ion chromatography to analyse the magnesium concentrations of public drinking waters in a representative sample of 108 Spanish municipalities (supplying 21,290,707 potential individuals) and 109 natural mineral waters sold in Spain (97 Spanish and 12 imported). The water generally contained between 15 and 45 mg/L of magnesium, but in seven municipalities it contained over 45 mg/L. The average magnesium concentration of 97 brands of Spanish natural mineral water was 16.27 mg/L (range: 0.11-141.2 mg/L). Of these, 33 contained between 15 and 45 mg/L of magnesium and four contained over 45 mg/L. Of the 12 imported brands, 4 contained over 45 mg/L. Assuming water consumption is as recommended by the European Food Safety Agency, water containing 15 to 45 mg/L of magnesium provides between 9 and 76.5% of the recommended intake of magnesium for children aged one to thirteen, up to 25.7% in adolescents, between 7.5 and 25.7% for adults, and up to 27% for lactating women. Water with 60 mg/L of magnesium provides between 30 and 102% of the recommended dietary allowance, depending on the age of the individual. The consumption of public drinking water and natural mineral water in a third of Spanish cities can be regarded as an important supplementary source of magnesium.


Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical squamous intraepithelial neoplasia.
A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli. Expression of p16 (p16), MIB-1 (Ki-67) labeling index, and HPV DNA detection and typing were performed on each case. The majority of EDs showed more than three atypical cells in an entire lesion but lack of apparent features of HSIL. It was common to find neighboring cervical squamous metaplasia and/or conventional SILs (either HSIL or low-grade squamous intraepithelial lesion [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen without any SILs in the entire specimens. Area of benign squamous metaplasia was found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41 (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10 HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high-risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases, the majority showed presence of dysplastic lesions of either HSIL or LSIL on either loop electric excision procedures or Papanicolaou test samples after a 6- to 10-week period. Therefore, ED represents an unrecognized and potentially clinically significant subgroup of cervical intraepithelial lesions. Based on the unique histologic appearance of ED, its association in some cases with HSIL, the overall immunohistochemical findings, frequent association of ED with intermediate- and/or high-risk HPV infection, and limited follow-up data, we believe that ED represents a variant of HSIL (CIN 2). Since ED possesses histologic features of both dysplasia and metaplasia, we speculate that it may arise from metaplastic cervical squamous epithelium that has subsequently become infected with intermediate- or high-risk HPV.


Comparison of Bioelectrical Impedance Analysis, Slaughter Skinfold-Thickness Equations, and Dual-Energy X-ray Absorptiometry for Estimating Body Fat Percentage in Colombian Children and Adolescents with Excess of Adiposity.
Dual-energy X-ray absorptiometry (DXA) has been considered a reference method for measuring body fat percentage (BF%) in children and adolescents with an excess of adiposity. However, given that the DXA technique is impractical for routine field use, there is a need to investigate other methods that can accurately determine BF%. We studied the accuracy of bioelectrical impedance analysis (BIA) technology, including foot-to-foot and hand-to-foot impedance, and Slaughter skinfold-thickness equations in the measurement of BF%, compared with DXA, in a population of Latin American children and adolescents with an excess of adiposity. A total of 127 children and adolescents (11⁻17 years of age; 70% girls) from the HEPAFIT (Exercise Training and Hepatic Metabolism in Overweight/Obese Adolescent) study were included in the present work. BF% was measured on the same day using two BIA analysers (Seca® 206, Allers Hamburg, Germany and Model Tanita® BC-418®, TANITA Corporation, Sportlife Tokyo, Japan), skinfold measurements (Slaughter equation), and DXA (Hologic Horizon DXA System®, Quirugil, Bogotá, Columbia). Agreement between measurements was analysed using t-tests, Bland⁻Altman plots, and Lin's concordance correlation coefficient (ρc). There was a significant correlation between DXA and the other BF% measurement methods (r > 0.430). According to paired t-tests, in both sexes, BF% assessed by BIA analysers or Slaughter equations differ from BF% assessed by DXA (p < 0.001). The lower and upper limits of the differences compared with DXA were 6.3⁻22.9, 2.2⁻2.8, and -3.2⁻21.3 (95% CI) in boys and 2.3⁻14.8, 2.4⁻20.1, and 3.9⁻18.3 (95% CI) in girls for Seca® mBCA, Tanita® BC 420MA, and Slaughter equations, respectively. Concordance was poor between DXA and the other methods of measuring BF% (ρc < 0.5). BIA analysers and Slaughter equations underestimated BF% measurements compared to DXA, so they are not interchangeable methods for assessing BF% in Latin American children and adolescents with excess of adiposity.


Evolutionary limits to cooperation in microbial communities.
Microbes produce many compounds that are costly to a focal cell but promote the survival and reproduction of neighboring cells. This observation has led to the suggestion that microbial strains and species will commonly cooperate by exchanging compounds. Here, we examine this idea with an ecoevolutionary model where microbes make multiple secretions, which can be exchanged among genotypes. We show that cooperation between genotypes only evolves under specific demographic regimes characterized by intermediate genetic mixing. The key constraint on cooperative exchanges is a loss of autonomy: strains become reliant on complementary genotypes that may not be reliably encountered. Moreover, the form of cooperation that we observe arises through mutual exploitation that is related to cheating and "Black Queen" evolution for a single secretion. A major corollary is that the evolution of cooperative exchanges reduces community productivity relative to an autonomous strain that makes everything it needs. This prediction finds support in recent work from synthetic communities. Overall, our work suggests that natural selection will often limit cooperative exchanges in microbial communities and that, when exchanges do occur, they can be an inefficient solution to group living.


Circadian Rhythms and Sleep in Drosophila melanogaster.
The advantages of the model organism Drosophila melanogaster, including low genetic redundancy, functional simplicity, and the ability to conduct large-scale genetic screens, have been essential for understanding the molecular nature of circadian (∼24 hr) rhythms, and continue to be valuable in discovering novel regulators of circadian rhythms and sleep. In this review, we discuss the current understanding of these interrelated biological processes in Drosophila and the wider implications of this research. Clock genes period and timeless were first discovered in large-scale Drosophila genetic screens developed in the 1970s. Feedback of period and timeless on their own transcription forms the core of the molecular clock, and accurately timed expression, localization, post-transcriptional modification, and function of these genes is thought to be critical for maintaining the circadian cycle. Regulators, including several phosphatases and kinases, act on different steps of this feedback loop to ensure strong and accurately timed rhythms. Approximately 150 neurons in the fly brain that contain the core components of the molecular clock act together to translate this intracellular cycling into rhythmic behavior. We discuss how different groups of clock neurons serve different functions in allowing clocks to entrain to environmental cues, driving behavioral outputs at different times of day, and allowing flexible behavioral responses in different environmental conditions. The neuropeptide PDF provides an important signal thought to synchronize clock neurons, although the details of how PDF accomplishes this function are still being explored. Secreted signals from clock neurons also influence rhythms in other tissues. SLEEP is, in part, regulated by the circadian clock, which ensures appropriate timing of sleep, but the amount and quality of sleep are also determined by other mechanisms that ensure a homeostatic balance between sleep and wake. Flies have been useful for identifying a large set of genes, molecules, and neuroanatomic loci important for regulating sleep amount. Conserved aspects of sleep regulation in flies and mammals include wake-promoting roles for catecholamine neurotransmitters and involvement of hypothalamus-like regions, although other neuroanatomic regions implicated in sleep in flies have less clear parallels. Sleep is also subject to regulation by factors such as food availability, stress, and social environment. We are beginning to understand how the identified molecules and neurons interact with each other, and with the environment, to regulate sleep. Drosophila researchers can also take advantage of increasing mechanistic understanding of other behaviors, such as learning and memory, courtship, and aggression, to understand how sleep loss impacts these behaviors. Flies thus remain a valuable tool for both discovery of novel molecules and deep mechanistic understanding of sleep and circadian rhythms.


A blended psychosocial support program for partners of patients with amyotrophic lateral sclerosis and progressive muscular atrophy: protocol of a randomized controlled trial.
Informal caregivers of patients with Amyotrophic Lateral Sclerosis (ALS) or Progressive Muscular Atrophy (PMA) face stressful demands due to severe impairments and prospect of early death of the patients they care for. Caregivers often experience feelings of psychological distress and caregiver burden, but supportive interventions are lacking. The objective of this study is to investigate the effectiveness of a psychosocial support program aimed at enhancing feelings of control over caregiving tasks and reducing psychological distress. This support program is based on an existing program for adult partners of people with cancer and is adapted to meet the needs of ALS caregivers. This study is a randomized controlled trial using a wait-list control design. One hundred and forty caregiver-patient dyads, recruited from a nationwide database and through the website of the Dutch ALS Center, will be either randomized to a support program or a wait-list control group. The blended intervention is based on Acceptance and Commitment Therapy and consists of 1 face-to-face contact, 6 online guided modules and 1 telephone contact. The intervention can be worked through in 8 weeks. The effectiveness and the participants' satisfaction with the intervention will be evaluated using a mixed method design. Caregivers and patients will be asked to fill in questionnaires on 4 occasions during the study: baseline, 3 months, 6 months and 9 months. The main study outcome is the psychological distress of the caregiver assessed with the Hospital Anxiety and Depression Scale. Secondary outcomes are caregiver burden, caregiver quality of life, quality of life of the patient and psychological distress of the patient. Group differences in primary and secondary outcomes at 6 months will be compared with linear mixed model analysis. In a subgroup of caregivers we will explore experiences with the support program through semi-structured interviews. Usage of the online modules will be logged. The study will provide insights into the effectiveness of a blended psychosocial support program on psychological distress of caregivers of patients with ALS or PMA, as well as into indirect relations with patients' wellbeing. Netherlands Trial Registry NTR5734 , registered 28 March 2016.


Zero-fringe demodulation method based on location-dependent birefringence dispersion in polarized low-coherence interferometry.
We present a high precision and fast speed demodulation method for a polarized low-coherence interferometer with location-dependent birefringence dispersion. Based on the characteristics of location-dependent birefringence dispersion and five-step phase-shifting technology, the method accurately retrieves the peak position of zero-fringe at the central wavelength, which avoids the fringe order ambiguity. The method processes data only in the spatial domain and reduces the computational load greatly. We successfully demonstrated the effectiveness of the proposed method in an optical fiber Fabry-Perot barometric pressure sensing experiment system. Measurement precision of 0.091 kPa was realized in the pressure range of 160 kPa, and computation time was improved by 10 times compared to the traditional phase-based method that requires Fourier transform operation.


Holographic grating based high sensitivity device for refractive index measurements.
In this communication, we show how a short-pitch diffractive structure can be used as a low-cost high sensitivity device for refractive index measurements with sensitivity of 10(-2). The device consists of a photo-resist diffraction grating put in optical contact with a hollow prism used as a container for a test material. Its main advantage is the possibility to monitor the composition of solids, fluids and gases in real time. Knowledge of optical parameters of a system with high accuracy can be vital when working in the biological/medical field.


[Antimicrobial susceptibility testing in clinically relevant non-fermenting gram-negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of the Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología].
This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.


Contextual considerations in summative competency examinations: relevance to the long case.
Long-case patient-based examinations previously formed the basis of summative competency testing in physician certification examinations. These exams were found to be unreliable and have fallen from favor. During the authors' deliberation of the long case in the neurology certification examinations of the Royal College of Physicians and Surgeons of Canada, they considered the examination context and concluded that the appropriate psychometric analysis of the exams is highly contingent on the context. The examination context underlying certification examinations has evolved considerably; within a different context, a more cohesive test system based on a quality assurance framework could better manage substantive psychometric issues around case specificity, comprehensiveness, reliability, and compensability. These arguments are in small part psychometric, but are mostly philosophical and have relevance to the profession and the public.


Fatal systemic air embolism during endoscopic retrograde cholangio-pancreatography.
Air embolism is a rare complication of gastrointestinal endoscopy. We present a 56-year-old male who developed both venous and systemic arterial air embolism during an endoscopic retrograde cholangiopancreatogram. Despite early treatment based on clinical diagnosis and confirmation by transthoracic echocardiography, the patient died as a result of severe cerebral ischaemia. Risk factors associated with air embolism in gastrointestinal endoscopic procedures include situations where the mucosa is not intact or where high pressures are generated in the lumen of the gastrointestinal tract. Clinical diagnosis of air embolism during endoscopy is difficult and urgent echocardiography is the investigation of choice. Treatment is largely supportive but hyperbaric oxygen therapy should be considered in any severe cases, especially if neurological injury is present.


NaLaW2O7(OH)2(H2O): Crystal Structure and RE3+ Luminescence in the Pristine and Annealed Double Tungstates (RE = Eu, Tb, Sm, and Dy).
Hydrothermal reaction of La(NO3)3 and Na2WO4·2H2O at 100 °C and pH 8 resulted in the formation of new compound NaLaW2O7(OH)2(H2O), as confirmed by the X-ray diffraction results, chemical composition, Fourier transform infrared, thermogravimetric/differential thermal analysis, and transmission electron microscopy analyses. The crystal structure was determined in the triclinic system (space group P1̅), with lattice constants a = 5.8671(2) Å, b = 8.2440(2) Å, and c = 9.0108(3) Å, axis angles α = 93.121(2)°, β = 75.280(2)°, and γ = 94.379(2)°, and cell volume V = 420.03(2) Å3. The structure contains two-dimensional layers of -(W1O6)-(W1O6)-(W2O6)-(W2O6)-(W1O6)-(W1O6)- and -LaO9-LaO9- chains alternating in the a-b plane, which are linked together through NaO6 octahedral trigonal prisms by edges to form a three-dimensional net. Dehydration of the compound proceeds up to a low temperature of ∼350 °C and results in the formation of technologically important NaLa(WO4)2 double tungstate, which is thus a unique precursor for the latter. Na(La,RE)W2O7(OH)2(H2O) and Na(La,RE)(WO4)2 solid solutions separately doped with the practically important activators for which RE = Eu, Tb, Sm, and Dy were also successfully synthesized and investigated for their structural features and photoluminescence properties, including excitation, emission, quantum yield, emission color, and fluorescence decay kinetics. The compounds were shown to exhibit dominantly strong red (∼616 nm for Eu3+; λex = 395 or 464 nm), green (∼545 nm for Tb3+; λex = 278 or 258 nm), deep red (∼645 nm for Sm3+; λex = 251 nm), and yellow (∼573 nm for Dy3+; λex = 254 nm) emission upon being irradiated with the peak wavelengths of their strongest excitation bands.


ANXIETY AND DEPRESSION DURING PREGNANCY AND TEMPERAMENT IN EARLY INFANCY: FINDINGS FROM A MULTI-ETHNIC, ASIAN, PROSPECTIVE BIRTH COHORT STUDY.
Maternal antenatal mood is associated with negative infant temperament. This link has not been substantiated in Asian populations. We evaluated the association between antenatal maternal mood and infant temperament among Asian mother-infant pairs. Antenatal maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987) and the State-Trait Anxiety Inventory (C. Spielberger, R. Gorsuch, R. Lushene, P. Vagg, & G. Jacobs, 1983), respectively, at 26 weeks of pregnancy and 3 months' postnatally. Infant temperament was evaluated with the Early Infant Temperament Questionnaire (B. Medoff-Cooper, W.B. Carey, & S.C. McDevitt, 1993) at 3 months. Factor analysis was performed to extract culturally relevant categories of temperamental traits. Linear regression was performed to examine the influences of antenatal maternal mood on the factor-model-derived infant temperament. Of the 609 mothers, 11% met risk criteria for depression, 17% for state-anxiety, and 19% for trait-anxiety during pregnancy. Factor analysis yielded three infant temperament factors: Emotionality and Attentional Regulation, Sensory Reactivity, and Regularity and Motor Expression, Cronbach's αs = 0.613, 0.712, and 0.752, respectively. Maternal antenatal state-anxiety, p < .001, and trait anxiety, p = .005, were associated with negative emotionality and poor attentional regulation, especially among Chinese, whereas depression was not, p = .090. There was an association between maternal antenatal anxiety and negative infant temperamental traits in this Asian sample.


An echelle spectrometer-spectrograph for astronomical use.
A compact echelle spectrometer-spectrograph has been designed for use at the Cassegrain focus of the University of Wisconsin 91-cm telescope at Pine Bluff. Laboratory results obtained with this instrument show that it has great potential for both stellar and nebular studies. Typical photographs and photoelectric scans of laboratory spectra are shown. A method of determining the profile of the echelle blaze is discussed. The instrument has high dispersion, 2.5 A/mm at 5000 A with a camera focal length of 0.5 m, and a spectral purity of 1.25 A/mm of entrance slit.


Location Sensitive Deep Convolutional Neural Networks for Segmentation of White Matter Hyperintensities.
The anatomical location of imaging features is of crucial importance for accurate diagnosis in many medical tasks. Convolutional neural networks (CNN) have had huge successes in computer vision, but they lack the natural ability to incorporate the anatomical location in their decision making process, hindering success in some medical image analysis tasks. In this paper, to integrate the anatomical location information into the network, we propose several deep CNN architectures that consider multi-scale patches or take explicit location features while training. We apply and compare the proposed architectures for segmentation of white matter hyperintensities in brain MR images on a large dataset. As a result, we observe that the CNNs that incorporate location information substantially outperform a conventional segmentation method with handcrafted features as well as CNNs that do not integrate location information. On a test set of 50 scans, the best configuration of our networks obtained a Dice score of 0.792, compared to 0.805 for an independent human observer. Performance levels of the machine and the independent human observer were not statistically significantly different (p-value = 0.06).


Cost-Effective Potential for Accurate Polarizable Embedding Calculations in Protein Environments.
The fragment-based polarizable embedding (PE) model combined with an appropriate electronic structure method constitutes a highly efficient and accurate multiscale approach for computing spectroscopic properties of a central moiety including effects from its molecular environment through an embedding potential. There is, however, a comparatively high computational overhead associated with the computation of the embedding potential, which is derived from first-principles calculations on individual fragments of the environment. To reduce the computational cost associated with the calculation of embedding potential parameters, we developed a set of amino acid-specific transferable parameters tailored for large-scale PE-based calculations that include proteins. The amino acid-based parameters are obtained by simultaneously fitting to a set of reference electric potentials based on structures derived from a backbone-dependent rotamer library. The developed cost-effective polarizable protein potential (CP3) consists of atom-centered charges and isotropic dipole-dipole polarizabilities of the standard amino acids. In terms of reproduction of electric potentials, the CP3 is shown to perform consistently and with acceptable accuracy across both small tripeptide test systems and larger proteins. We show, through applications on realistic protein systems, that acceptable accuracy can be obtained by using a pure CP3 representation of the protein environment, thus altogether omitting the cost associated with the calculation of embedding potential parameters. High accuracy comparable to that of the full fragment-based approach can be achieved through a mixed description where the CP3 is used only to describe amino acids beyond a threshold distance from the central quantum part.


Contemporary management of comorbid anxiety and depression in geriatric patients.
Anxiety and depression in elderly people are major public health problems in the United States. Recognition and treatment of these conditions will likely gain more attention in the next 30 to 50 years because of the projected growth of the geriatric population. As in many younger patients, the most common presentation of anxiety in elderly patients is comorbid anxiety and depression. Although age is not a risk factor for either anxiety or depression, factors associated with aging--such as increased medical burdens and loss of independence--are substantial risk factors for development of these conditions. Moreover, there is a close association in older people between untreated mental illness and exacerbation of physical illness. Some of the newer antidepressants are more appropriate long-term options for the treatment of comorbid anxiety and depression than either benzodiazepines or tricyclic antidepressants. The newer antidepressants can decrease symptoms, improve quality of life, and potentially promote healthier outcomes in geriatric patients who have comorbid anxiety and depression and/or comorbid mental and physical illness.


Phase nucleation through confined spinodal fluctuations at crystal defects evidenced in Fe-Mn alloys.
Analysis and design of materials and fluids requires understanding of the fundamental relationships between structure, composition, and properties. Dislocations and grain boundaries influence microstructure evolution through the enhancement of diffusion and by facilitating heterogeneous nucleation, where atoms must overcome a potential barrier to enable the early stage of formation of a phase. Adsorption and spinodal decomposition are known precursor states to nucleation and phase transition; however, nucleation remains the less well-understood step in the complete thermodynamic sequence that shapes a microstructure. Here, we report near-atomic-scale observations of a phase transition mechanism that consists in solute adsorption to crystalline defects followed by linear and planar spinodal fluctuations in an Fe-Mn model alloy. These fluctuations provide a pathway for austenite nucleation due to the higher driving force for phase transition in the solute-rich regions. Our observations are supported by thermodynamic calculations, which predict the possibility of spinodal decomposition due to magnetic ordering.


Role of Sputter Deposition Rate in Tailoring Nanogranular Gold Structures on Polymer Surfaces.
The reproducible low-cost fabrication of functional polymer-metal interfaces via self-assembly is of crucial importance in organic electronics and organic photovoltaics. In particular, submonolayer and nanogranular systems expose highly interesting electrical, plasmonic, and catalytic properties. The exploitation of their great potential requires tailoring of the structure on the nanometer scale and below. To obtain full control over the complex nanostructural evolution at the polymer-metal interface, we monitor the evolution of the metallic layer morphology with in situ time-resolved grazing-incidence small-angle X-ray scattering during sputter deposition. We identify the impact of different deposition rates on the growth regimes: the deposition rate affects primarily the nucleation process and the adsorption-mediated growth, whereas rather small effects on diffusion-mediated growth processes are observed. Only at higher rates are initial particle densities higher due to an increasing influence of random nucleation, and an earlier onset of thin film percolation occurs. The obtained results are discussed to identify optimized morphological parameters of the gold cluster ensemble relevant for various applications as a function of the effective layer thickness and deposition rate. Our study opens up new opportunities to improve the fabrication of tailored metal-polymer nanostructures for plasmonic-enhanced applications such as organic photovoltaics and sensors.


Beyond oversights, lies, and pies in the sky: exaggeration as goal projection.
The adaptiveness of overly positive self-evaluation is heavily debated. The present research emphasizes that costs and benefits of positive biases are contingent upon their underlying motives. Five studies explored psychological and performance correlates of the tendency to exaggerate academic performance. Students who exaggerated in a private reporting context showed greater achievement motivation and positive affect (Study 1), challenge and approach orientations (Study 2), and observer-rated composure during a stressful mock job interview (Study 3). Moreover, exaggeration predicted subsequent academic improvements. This form of exaggeration apparently reflects an adaptive tendency to project positive goals onto self-reports. In contrast, exaggeration in a more public context was associated with social desirability motives and not with positive affect, approach/challenge motives, or improvement (Study 4). Making actual performance salient (by highlighting that records would be checked) reduced exaggeration; students who exaggerated in this context did not improve over time, instead showing performance decrements (Study 5).


Underprescribing of clozapine and unexplained variation in use across hospitals and regions in the Canadian province of Québec.
Clozapine remains the antipsychotic of choice for people who, having met the criteria for a diagnosis of schizophrenia or a related psychotic disorder, do not respond adequately to other antipsychotic medications. Utilization rates appear highly variable across jurisdictions, with an overall tendency toward underuse. This paper describes patterns of clozapine use in the province of Québec, Canada. Individuals with a diagnosis of schizophrenia were identified using linked government medical claims and hospitalization records for 2003 and 2004. Linked data on their filled prescriptions in 2004 were then used to determine clozapine-use rates at the level of the province, the region, and the hospital at which individuals received most of their services. Individual predictors of clozapine use were identified using logistic regression. Only 6.7% of the 29,155 individuals identified with schizophrenia received clozapine for six months or longer in 2004. Utilization rates ranged from 3.9 to 9.0% among regions with 1,000 or more people with schizophrenia. Over 8% of 61 hospitals did not prescribe clozapine at all. People with schizophrenia taking clozapine experienced 3.4 fewer days of hospitalization per year than those not taking clozapine-representing a cost offset of about $1,800 per year. Medication costs were higher, however, by about $3,000 per year. Given the increasingly clear benefits of clozapine for people who do not respond to other antipsychotics, measures to increase access to clozapine for people who can benefit from it are likely to be cost effective and are urgently needed.


In vitro and in vivo contractile properties of the vastus lateralis muscle in males with COPD.
Peripheral muscle weakness is common in chronic obstructive pulmonary disease (COPD) but it is still under debate whether weakness is due to atrophy or contractile dysfunction. In vitro and in vivo contractile properties of the vastus lateralis muscle were studied in 16 patients with stable COPD (forced expiratory volume in one second 39 +/- 16% of predicted, age 67 +/- 4 yrs (mean +/- sD)) and nine sedentary control subjects. Isometric knee extensor strength was measured while mid-thigh muscle cross-sectional area (MTMCSA) was obtained using computed tomography. Muscle strips from the vastus lateralis obtained through open biopsy were rapidly suspended in an oxygenated Krebs-Ringer solution that was maintained at 35 degrees C with a pH of 7.40 to study their contractile properties. The isometric knee extensors strength/MTMCSA ratio was 0.50 +/- 0.08 versus 0.58 +/- 0.06 kg x cm(-2) for COPD and control subjects, respectively. The muscle bundle cross-sectional area (CSA) was 4.6 +/- 2.1 and 4.4 +/- 3.1 mm(-2), the length at which active tension was maximum was 15 +/- 4 and 15 +/- 3 mm, and maximal isometric peak forces normalised for CSA were 4.3 +/- 2.7 and 4.8 +/- 2.6 N x cm(-2) for COPD and control subjects, respectively. The force/frequency relationship tended to be shifted to the right in patients with COPD, meaning that a higher stimulation frequency was necessary to produce the same relative force. Patients with COPD had a lower proportion of type I fibre than controls (26 +/- 12% versus 39 +/- 11%) with reciprocal significant increase in type IIb fibre proportion (20+/-16% versus 8 +/- 4%). The proportion of type IIa fibres was similar between the two groups. These results suggest that the contractile properties of the vastus lateralis are preserved in patients with chronic obstructive pulmonary disease. Therefore, the reduction in the quadriceps strength in patients with chronic obstructive pulmonary disease cannot be explained on the basis of an alteration of the contractile apparatus.


Surgical treatment in patient with non-small-cell lung cancer with fissure involvement: anatomical versus nonanatomical resection.
Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non-small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. From January 2000 to January 2010, the clinical data of 40 non-small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ, and log-rank tests, Kaplan-Meier method, and Cox and logistic regression analyses were used for the statistical analysis. No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (-24.9% ± 13.5%) when compared with that in group B (-19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life.


Gastric volvulus in children: experience of 6 years at a tertiary care centre.
The aim of the study was to review the cases of all children who had gastric volvulus from 2002 to 2007 at a tertiary care centre in India and to compare the outcome of management with the reported series on gastric volvulus in a paediatric age group. This was a retrospective study of eight children with an age range between 10 days and 2 years who were managed for gastric volvulus between 2002 and 2007. The records of these patients were reviewed for clinical features, investigations, management and outcome. All patients were less than 3 years of age with female preponderance (n = 5). Three patients had acute presentation and three had acute-on-chronic symptoms, while two had chronic gastric volvulus. The commonest symptom was abdominal distension. Two patients were diagnosed by barium studies and six had clinical suspicion because of their symptoms and were confirmed intra-operatively. Seven had secondary gastric volvulus of organo axial type with associated pathologies as congenital diaphragmatic hernia (n = 5), Para oesophageal hiatus hernia (n = 2), and one had primary gastric volvulus in a postoperative period in an operated case for a tracheo-oesophageal fistula (n = 1). Seven patients were symptom free at follow-up; one patient succumbed due to septicaemia in the immediate post-operative period which was not related to the pathology of gastric volvulus. Gastric volvulus is a rare condition in children and requires prompt diagnosis and urgent intervention in acute presentation where it mimics acute abdomen and strong clinical suspicion.


Neuroimaging in Dementia: A Brief Review.
Dementia is a clinical syndrome that manifests itself with impairment in cognitive functions owing to various neurodegenerative etiologies causing severe disability in the older population. Although the diagnosis is largely dependent on clinical examination, biomarkers can significantly aid in early diagnosis of dementia, especially in those without any clinical evidence of neurocognitive impairment. These biomarkers can be discovered in cerebrospinal fluid (CSF) or can be assessed by neuroimaging. Our goal was to discuss and assess the role of different neuroimaging techniques in the early diagnosis of relatively common etiologies of dementia. We used PubMed as search engines to look for helpful articles; most of the sources used were peer reviewed. We discussed the utility of various neuroimaging techniques, such CT, MRI, positron emission tomography (PET) scan, and single-photon emission computed tomography (SPECT), in the diagnosis of dementia. We concluded that various modern neuroimaging techniques prove to be very helpful in early identification, diagnosis, and differentiation between subtypes. However, the actual clinical utility of these tests in terms of their cost-effectivity and availability remains to be seen. Ongoing research is required to further develop biomarkers for early identification and monitor the progression of different etiologies of dementia.


Biphasic cellular adaptations and ecological implications of Alteromonas macleodii degrading a mixture of algal polysaccharides.
Algal polysaccharides are an important bacterial nutrient source and central component of marine food webs. However, cellular and ecological aspects concerning the bacterial degradation of polysaccharide mixtures, as presumably abundant in natural habitats, are poorly understood. Here, we contextualize marine polysaccharide mixtures and their bacterial utilization in several ways using the model bacterium Alteromonas macleodii 83-1, which can degrade multiple algal polysaccharides and contributes to polysaccharide degradation in the oceans. Transcriptomic, proteomic and exometabolomic profiling revealed cellular adaptations of A. macleodii 83-1 when degrading a mix of laminarin, alginate and pectin. Strain 83-1 exhibited substrate prioritization driven by catabolite repression, with initial laminarin utilization followed by simultaneous alginate/pectin utilization. This biphasic phenotype coincided with pronounced shifts in gene expression, protein abundance and metabolite secretion, mainly involving CAZymes/polysaccharide utilization loci but also other functional traits. Distinct temporal changes in exometabolome composition, including the alginate/pectin-specific secretion of pyrroloquinoline quinone, suggest that substrate-dependent adaptations influence chemical interactions within the community. The ecological relevance of cellular adaptations was underlined by molecular evidence that common marine macroalgae, in particular Saccharina and Fucus, release mixtures of alginate and pectin-like rhamnogalacturonan. Moreover, CAZyme microdiversity and the genomic predisposition towards polysaccharide mixtures among Alteromonas spp. suggest polysaccharide-related traits as an ecophysiological factor, potentially relating to distinct 'carbohydrate utilization types' with different ecological strategies. Considering the substantial primary productivity of algae on global scales, these insights contribute to the understanding of bacteria-algae interactions and the remineralization of chemically diverse polysaccharide pools, a key step in marine carbon cycling.


Generalized wavefront phase for non-Kolmogorov turbulence.
We introduce the Lévy fractional Brownian field family to model the turbulent wavefront phase. This generalized model allows us to overcome the limitations found in a previous approach [Perez et al., J. Opt. Soc. Am. A 21, 1962 (2004)]. More precisely, our new model provides stationary phase increments over the full inertial range. Thus it successfully extends classical results to non-Kolmogorov turbulence without any approximation.


Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study.
Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points. We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies. Levels of alkaline phosphatase and bilirubin were analyzed in different settings and subpopulations at different time points relative to the clinical end point (liver transplantation or death). Of the 4845 patients, 1118 reached a clinical end point. The median follow-up period was 7.3 years; 77% survived for 10 years after study enrollment. Levels of alkaline phosphatase and bilirubin measured at study enrollment (baseline) and each year for 5 years were strongly associated with clinical outcomes (lower levels were associated with longer transplant-free survival). At 1 year after study enrollment, levels of alkaline phosphatase that were 2.0 times the upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other thresholds. Of patients with alkaline phosphatase levels ≤ 2.0 times the ULN, 84% survived for 10 years compared with 62% of those with levels >2.0 times the ULN (P < .0001). Absolute levels of alkaline phosphatase 1 year after study enrollment predicted patient outcomes better than percentage change in level. One year after study enrollment, a bilirubin level 1.0 times the ULN best predicted patient transplant-free survival (C statistic, 0.79). Of patients with bilirubin levels ≤ 1.0 times the ULN, 86% survived for 10 years after study enrollment compared with 41% of those with levels >1.0 times the ULN (P < .0001). Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times. We confirmed the predictive value of alkaline phosphatase and bilirubin levels in multiple subgroups, such as patients who had not received treatment with ursodeoxycholic acid, and at different time points after study enrollment. Levels of alkaline phosphatase and bilirubin can predict outcomes (liver transplantation or death) of patients with PBC and might be used as surrogate end points in therapy trials.


Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016.
Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1 and blaCMY-6, as well as chromosomal blaCTX-M-15 and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.


Optical image quality and the cone mosaic.
Contrary to the orthodox view that optical image quality should "match" the photoreceptor grain, anatomical data from the eyes of various animals suggest that the image quality is significantly superior to the potential resolution of the cone mosaic in most retinal regions. A new theory is presented to explain the existence of this relation and to better appreciate eye design. It predicts that photoreceptors are potentially visible through the natural optics.


Review of Croatian genetic heritage as revealed by mitochondrial DNA and Y chromosomal lineages.
The aim of this review is to summarize the existing data collected in high-resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in 451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of Croatians can be adequately explained within typical European maternal and paternal genetic landscape, with the exception of mtDNA haplogroup F and Y-chromosomal haplogroup P* which indicate a connection to Asian populations. Similar to other European and Near Eastern populations, the most frequent mtDNA haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532 (25%), as well as the observed structuring of Y chromosomal variance reveal a clearly evident Slavic component in the paternal gene pool of contemporary Croatian men. Even though each population and groups of populations are well characterized by maternal and paternal haplogroup distribution, it is important to keep in mind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.


Assessment of Toxicity and Absorption of the Novel AA Derivative AA-Pme in SGC7901 Cancer Cells In Vitro and in Zebrafish In Vivo.
BACKGROUND Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is an active compound derived from Centella asiatica, a traditional medicinal plant used widely in many Asian countries, particularly for the treatment of cancer. However, the modified AA derivative N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe) has shown markedly better anti-tumor activity than AA. MATERIAL AND METHODS We evaluated the toxicity of AA and AA-PMe on zebrafish morphology, mortality, and hatching rate and determined the effect on SGC7901 cancer cells by acute toxicity assay. AA-PMe absorption in vitro in SGC7901 cells and in vivo in zebrafish was determined by establishing a highly accurate and reproducible HPLC protocol. RESULTS In zebrafish, the toxicity of AA-PMe was lower than AA, with an acute toxic dose of AA-PMe above 25 μM, compared to acute toxicity at doses above 10 μM for AA. However, chronic toxicity of AA-PMe began occurring at doses below 25 μM but became apparent for AA at doses below 10 μM. Although low doses of AA-PMe were tolerated acutely, it became chronically toxic during zebrafish development, resulting in morphological abnormalities, including peripheral and abdominal edema, hemorrhage, abnormal body shape, enlarged yolk sac, and reduced motility. At low concentrations, absorption of AA-PMe by cells and zebrafish embryos occurred in a dose-dependent manner, but this stabilized as the concentration increased. CONCLUSIONS This pharmacokinetic study outlines the cellular and organismal effects of AA-PMe and suggests a theoretical basis that may underlie its mechanism of action.


Combination of spectral and binaurally created harmonics in a common central pitch processor.
A fundamental attribute of human hearing is the ability to extract a residue pitch from harmonic complex sounds such as those produced by musical instruments and the human voice. However, the neural mechanisms that underlie this processing are unclear, as are the locations of these mechanisms in the auditory pathway. The ability to extract a residue pitch corresponding to the fundamental frequency from individual harmonics, even when the fundamental component is absent, has been demonstrated separately for conventional pitches and for Huggins pitch (HP), a stimulus without monaural pitch information. HP is created by presenting the same wideband noise to both ears, except for a narrowband frequency region where the noise is decorrelated across the two ears. The present study investigated whether residue pitch can be derived by combining a component derived solely from binaural interaction (HP) with a spectral component for which no binaural processing is required. Fifteen listeners indicated which of two sequentially presented sounds was higher in pitch. Each sound consisted of two "harmonics," which independently could be either a spectral or a HP component. Component frequencies were chosen such that the relative pitch judgement revealed whether a residue pitch was heard or not. The results showed that listeners were equally likely to perceive a residue pitch when one component was dichotic and the other was spectral as when the components were both spectral or both dichotic. This suggests that there exists a single mechanism for the derivation of residue pitch from binaurally created components and from spectral components, and that this mechanism operates at or after the level of the dorsal nucleus of the lateral lemniscus (brainstem) or the inferior colliculus (midbrain), which receive inputs from the medial superior olive where temporal information from the two ears is first combined.


Experimental investigation of the shear strengths of teeth in the region of the dentinoenamel junction.
The shear strengths of human incisors, canines, premolars, and molars and bovine incisors in the region of the dentinoenamel junction were tested. The median shear strength of all human teeth, 38.99 MPa, was not significantly different from that of bovine teeth, 37.40 MPa. Among the groups of human teeth, the highest median shear strength was obtained from mandibular premolars (46.15 MPa), and the lowest from mandibular canines (32.63 MPa). Physical treatments (cooling or drying) led to a significant reduction in shear strengths. A similar effect was found after exposure to amino butyrate (a caries-removing agent) but not after exposure to sodium hypochlorite (used in endodontic treatment). In all investigated groups of teeth, the fracture areas were mainly in dentin and never exactly at the dentinoenamel junction; indicating that the cohesion of dentin, not the adhesion between dentin and enamel, is the limiting factor in the shear strength.


Interrater Reproducibility of Knee Movement Analyses during the Stance Phase: Use of Anatomical Landmark Calibration with a Rigid Marker Set.
Objective. Measurements of knee joint movement in gait analysis may result in large errors caused by misplacement of reflective markers by the testers. To properly understand the measurement results, it is important to guarantee the reliability of the measurement method used for the purpose. The aim of this study was to confirm the interrater reproducibility of a measurement method with a rigid marker set (RMS). Methods. The study subjects were four healthy adults, and the testers were three physical therapists. The interrater reproducibility of the measurements was verified by using the coefficient of multiple correlations (CMCs) and the standard error of measurement (SEM). Results. The average CMCs values of 4 subjects in knee joint movement at the stance phase were greater than 0.8, and the average SEM values of 4 subjects in knee joint movement at the stance phase were also relatively good (maximum error: 2.42°). Conclusion. Based on these results, the measurement method with estimation of anatomical landmarks using the RMS can prevent misplacement during attachment of the reflective markers, as long as the testers have sufficient experience in attaching reflective markers.


Understanding phylogenetic incongruence: lessons from phyllostomid bats.
All characters and trait systems in an organism share a common evolutionary history that can be estimated using phylogenetic methods. However, differential rates of change and the evolutionary mechanisms driving those rates result in pervasive phylogenetic conflict. These drivers need to be uncovered because mismatches between evolutionary processes and phylogenetic models can lead to high confidence in incorrect hypotheses. Incongruence between phylogenies derived from morphological versus molecular analyses, and between trees based on different subsets of molecular sequences has become pervasive as datasets have expanded rapidly in both characters and species. For more than a decade, evolutionary relationships among members of the New World bat family Phyllostomidae inferred from morphological and molecular data have been in conflict. Here, we develop and apply methods to minimize systematic biases, uncover the biological mechanisms underlying phylogenetic conflict, and outline data requirements for future phylogenomic and morphological data collection. We introduce new morphological data for phyllostomids and outgroups and expand previous molecular analyses to eliminate methodological sources of phylogenetic conflict such as taxonomic sampling, sparse character sampling, or use of different algorithms to estimate the phylogeny. We also evaluate the impact of biological sources of conflict: saturation in morphological changes and molecular substitutions, and other processes that result in incongruent trees, including convergent morphological and molecular evolution. Methodological sources of incongruence play some role in generating phylogenetic conflict, and are relatively easy to eliminate by matching taxa, collecting more characters, and applying the same algorithms to optimize phylogeny. The evolutionary patterns uncovered are consistent with multiple biological sources of conflict, including saturation in morphological and molecular changes, adaptive morphological convergence among nectar-feeding lineages, and incongruent gene trees. Applying methods to account for nucleotide sequence saturation reduces, but does not completely eliminate, phylogenetic conflict. We ruled out paralogy, lateral gene transfer, and poor taxon sampling and outgroup choices among the processes leading to incongruent gene trees in phyllostomid bats. Uncovering and countering the possible effects of introgression and lineage sorting of ancestral polymorphism on gene trees will require great leaps in genomic and allelic sequencing in this species-rich mammalian family. We also found evidence for adaptive molecular evolution leading to convergence in mitochondrial proteins among nectar-feeding lineages. In conclusion, the biological processes that generate phylogenetic conflict are ubiquitous, and overcoming incongruence requires better models and more data than have been collected even in well-studied organisms such as phyllostomid bats.


Near-Infrared Light Manipulated Chemoselective Reductions Enabled by an Upconversional Supersandwich Nanostructure.
Core-satellite is one of the most powerful superstructures since it leads to enhanced or completely new properties through compatible combination of each component. Here we create a novel ceria-based core-shell-satellite supersandwich structure with near-infrared (NIR) light manipulated catalytic activity by integrating the upconversion luminescent and catalytic functionality of CeO2 nanoparticles. Specifically, lanthanide-doped octahedral CeO2 nanoparticles (o-CeO2) are coated with silica layer (o-CeO2@SiO2) to enhance their luminescence intensity. The pH-dependent catalytic active cubic CeO2 nanoparticles (c-CeO2) are then assembled on the surface of o-CeO2@SiO2 to form the supersandwich structure (o-CeO2@SiO2@c-CeO2) following a classic chemical reaction. The upconversion quantum yield of o-CeO2 in this nanostructure can be nearly doubled. Furthermore, under NIR light irradiation, the o-CeO2@SiO2@c-CeO2 supersandwich structure based composite catalyst displays superior catalytic activity in selective reduction of aromatic nitro compounds to corresponding azo compounds, and the composite photocatalyst can be easily recycled for several times without significant loss of catalytic activity. This strategy may serve as a universal method for the construction of multifunctional nanostructures and shed light on the green chemistry for chemical synthesis.


Derived no-effect levels (DNELs) under the European chemicals regulation REACH--an analysis of long-term inhalation worker-DNELs presented by industry.
The European REACH regulation places responsibility for providing safety information, including derived no-effect levels (DNELs), on chemicals and chemical products on 'industry', i.e. manufacturers and importers. We compared long-term inhalation worker-DNELs (wDNELs) presented by industry with the corresponding Swedish occupational exposure limits (OELs), and for a subset, with wDNELs derived by us. Our wDNELs were derived using toxicological evaluations published by the Swedish Criteria Group and our interpretation of the REACH Guidance. On average, industry's wDNELs were the same as the Swedish OELs (median of wDNEL-OEL ratios: 0.98, n = 235). However, the variation was huge, the extremes being up to 450 times higher, and up to 230 times lower than the corresponding OEL. Nearly one-fifth of the wDNELs were ≥2 times higher and one-third ≥2 times lower than the OEL. No time trend was seen in the wDNEL/OEL ratios, suggesting that older OELs were not systematically higher than the more recent ones. Industry's wDNELs varied widely and were generally higher (median 4.2 times, up to 435 times higher, down to 13 times lower, n = 23) also compared to our wDNELs. Only five industry wDNELs were equal to or lower than ours. The choices of key studies, dose descriptors, and assessment factors all seemed to contribute to the discrepancies. We conclude that although the REACH guidance is detailed, many choices that will influence the wDNEL lack firm instructions. A major problem is that little advice is given on when and how to depart from default assessment factors.


Assessment of the water quality and ecosystem health of the Great Barrier Reef (Australia): conceptual models.
Run-off containing increased concentrations of sediment, nutrients, and pesticides from land-based anthropogenic activities is a significant influence on water quality and the ecologic conditions of nearshore areas of the Great Barrier Reef World Heritage Area, Australia. The potential and actual impacts of increased pollutant concentrations range from bioaccumulation of contaminants and decreased photosynthetic capacity to major shifts in community structure and health of mangrove, coral reef, and seagrass ecosystems. A detailed conceptual model underpins and illustrates the links between the main anthropogenic pressures or threats (dry-land cattle grazing and intensive sugar cane cropping) and the production of key contaminants or stressors of Great Barrier Reef water quality. The conceptual model also includes longer-term threats to Great Barrier Reef water quality and ecosystem health, such as global climate change, that will potentially confound direct model interrelationships. The model recognises that system-specific attributes, such as monsoonal wind direction, rainfall intensity, and flood plume residence times, will act as system filters to modify the effects of any water-quality system stressor. The model also summarises key ecosystem responses in ecosystem health that can be monitored through indicators at catchment, riverine, and marine scales. Selected indicators include riverine and marine water quality, inshore coral reef and seagrass status, and biota pollutant burdens. These indicators have been adopted as components of a long-term monitoring program to enable assessment of the effectiveness of change in catchment-management practices in improving Great Barrier Reef (and adjacent catchment) water quality under the Queensland and Australian Governments' Reef Water Quality Protection Plan.


Architectural and performance considerations for a 10(7)-instruction/sec optoelectronic central processing unit.
Architectural considerations for a multiple-instruction, single-data-based optoelectronic central processing unit operating at 10(7) instructions per second are detailed. Central to the operation of this device is a giant fiber-optic content-addressable memory in a programmable logic array configuration. The design includes four instructions and emphasizes the fan-in and fan-out capabilities of optical systems. Interconnection limitations and scaling issues are examined.


Synthesis, absolute configuration, and bacterial mutagenicity of the 8 stereoisomeric vicinal diol epoxides at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene.
The synthesis of the 8 possible stereoisomeric diol epoxides (DEs) at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene (DBA) is reported. trans-3,4-Dihydroxy-3,4-dihydro-DBA (1) afforded the 4 bay region DEs: the enantiomeric pairs of the anti diastereomers (+)-3/(-)-3 and of the syn diastereomers (-)-4/(+)-4, respectively. trans-1,2-Dihydroxy-1,2-dihydro-DBA (2) served as precursor of the 4 reverse DEs: the enantiomeric pairs of the anti diastereomers (+)-5/(-)-5 and of the syn diastereomers (-)-6/(+)-6, respectively. The transformation of the olefinic double bond in the enantiomeric trans-dihydrodiols to epoxides was achieved by either (i) oxidation with m-chloroperoxybenzoic acid or (ii) formation of a bromohydrin with N-bromoacetamide/H(2)O followed by dehydrobromination with an anion exchange resin. Because of the pseudodiequatorial conformation of the hydroxyl groups in 1, both reactions proceeded highly stereoselectively, while the stereoselectivity was impaired by the pseudodiaxial conformation of the hydroxyl groups in 2. Diastereomers and racemic compounds were efficiently separated without derivatization by HPLC on achiral or chiral stationary phases, respectively. The absolute configurations of the DEs were deduced from the absolute configuration of 1 and 2 considering the regio- and stereoselectivity of the subsequent reactions and resulted in (+)-(1R,2S,3S,4R)-3/(-)-(1S,2R,3R,4S)-3, (-)-(1S,2R,3S,4R)-4/(+)-(1R,2S,3R,4S)-4, (+)-(1R,2S,3S,4R)-5/(-)-(1S,2R,3R,4S)-5, and (-)-(1R,2S,3R,4S)-6/(+)-(1S,2R,3S,4R)-6. The bacterial mutagenicity of the 8 stereoisomeric DEs was determined in histidine-dependent strains TA98 and TA100 of Salmonella typhimurium in the absence of a metabolizing system. In general, the bay region DEs of DBA were stronger mutagens than the reverse DEs. In strain TA98, the syn diastereomers of bay region DEs were stronger mutagens than their anti isomers, while in the case of reverse DEs the anti diastereomers were more potent than their syn isomers. In strain TA100, all syn diastereomers surpassed the bacterial mutagenicity of their anti isomers. Concerning the bay region DEs of DBA, this corresponds to the situation described for benzo[a]pyrene: of the 4 enantiomeric bay region DEs of DBA and benzo[a]pyrene, the syn diastereomer with [(R,S)-diol (R,S)-epoxide] absolute configuration is the most potent mutagen in both bacterial strains, while the anti isomer with [(S,R)-diol (R,S)-epoxide] configuration is the weakest mutagen.


Evaluation of the Efficacy and Safety of 308-nm Monochromatic Excimer Lamp in the Treatment of Resistant Alopecia Areata.
Treatment of resistant alopecia areata (AA) can be very challenging and include many options with variable efficacy and safety profiles. The 308-nm excimer lamp has been claimed to offer an effective alternative without significant risks, though there exists a lack of guidelines in this setting. This study aimed to evaluate the efficacy and safety of the 308-nm excimer lamp in treating resistant AA in Iraqi patients. A prospective interventional study. Eighteen patients with multiple AA were enrolled in this study. All patients were treated with a 308-nm monochromatic excimer lamp, in two sessions per week for 12 weeks. The efficacy of this modality was evaluated using two methods, namely the Severity of Alopecia Tool (SALT) score and digital photographs which were taken at four points (baseline, 4 weeks, 8 weeks, and 12 weeks). The safety of the equipment was evaluated by the objective recording of adverse reactions and patient satisfaction. Follow-up continued for 6 months after treatment to assess the level of recurrence. SPSS software version 23. There was a statistically significant decrease in the SALT score from the baseline (range 11-30; mean 20.33 ± standard deviation [SD] 4.78) to 12 weeks (range 2-24; mean 9.11 ± SD 5.41) (P < 0.001). The overall response rate was 100%, and successful (>50%) regrowth of hair was seen in 55.5% of patients (n = 10). Younger patients responded to the treatment more than the older age group (P < 0.05). No significant side effects were recorded. The results suggest that 308-nm excimer light has a significant effect on resistant cases of multiple AA, with considerable safety and tolerability.


An international prospective cohort study of mobile phone users and health (Cosmos): design considerations and enrolment.
There is continuing public and scientific interest in the possibility that exposure to radiofrequency (RF) electromagnetic fields (EMF) from mobile telephones or other wireless devices and applications might increase the risk of certain cancers or other diseases. The interest is amplified by the rapid world-wide penetration of such technologies. The evidence from epidemiological studies published to date have not been consistent and, in particular, further studies are required to identify whether longer term (well beyond 10 years) RF exposure might pose some health risk. The "Cosmos" study described here is a large prospective cohort study of mobile telephone users (ongoing recruitment of 250,000 men and women aged 18+ years in five European countries - Denmark, Finland, Sweden, The Netherlands, UK) who will be followed up for 25+ years. Information on mobile telephone use is collected prospectively through questionnaires and objective traffic data from network operators. Associations with disease risks will be studied by linking cohort members to existing disease registries, while changes in symptoms such as headache and sleep quality and of general well-being are assessed by baseline and follow-up questionnaires. A prospective cohort study conducted with appropriate diligence and a sufficient sample size, overcomes many of the shortcomings of previous studies. Its major advantages are exposure assessment prior to the diagnosis of disease, the prospective collection of objective exposure information, long-term follow-up of multiple health outcomes, and the flexibility to investigate future changes in technologies or new research questions.


A cellular perspective on brain energy metabolism and functional imaging.
The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales.


Foraging area fidelity for Kemp's ridleys in the Gulf of Mexico.
For many marine species, locations of key foraging areas are not well defined. We used satellite telemetry and switching state-space modeling (SSM) to identify distinct foraging areas used by Kemp's ridley turtles (Lepidochelys kempii) tagged after nesting during 1998-2011 at Padre Island National Seashore, Texas, USA (PAIS; N = 22), and Rancho Nuevo, Tamaulipas, Mexico (RN; N = 9). Overall, turtles traveled a mean distance of 793.1 km (±347.8 SD) to foraging sites, where 24 of 31 turtles showed foraging area fidelity (FAF) over time (N = 22 in USA, N = 2 in Mexico). Multiple turtles foraged along their migratory route, prior to arrival at their "final" foraging sites. We identified new foraging "hotspots" where adult female Kemp's ridley turtles spent 44% of their time during tracking (i.e., 2641/6009 tracking days in foraging mode). Nearshore Gulf of Mexico waters served as foraging habitat for all turtles tracked in this study; final foraging sites were located in water <68 m deep and a mean distance of 33.2 km (±25.3 SD) from the nearest mainland coast. Distance to release site, distance to mainland shore, annual mean sea surface temperature, bathymetry, and net primary production were significant predictors of sites where turtles spent large numbers of days in foraging mode. Spatial similarity of particular foraging sites selected by different turtles over the 13-year tracking period indicates that these areas represent critical foraging habitat, particularly in waters off Louisiana. Furthermore, the wide distribution of foraging sites indicates that a foraging corridor exists for Kemp's ridleys in the Gulf. Our results highlight the need for further study of environmental and bathymetric components of foraging sites and prey resources contained therein, as well as international cooperation to protect essential at-sea foraging habitats for this imperiled species.


Radioimmunotherapy of CD22-expressing Daudi tumors in nude mice with a 90Y-labeled anti-CD22 monoclonal antibody.
A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22 monoclonal antibody for selectively delivering high-energy (90)Y radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was readily labeled with (90)Y using the highly stable chelate, 1B4M-diethylenetriaminepentaacetic acid. Labeled RFB4 selectively bound to the CD22(+) Burkitt's lymphoma cell line Daudi, but not to CD22(-) control cells in vitro as compared with a control antibody, and was more significantly bound (P = 0.03) to Daudi solid tumors growing in athymic nude mice. Biodistribution data correlated well with the antitumor effect. The therapeutic effect of (90)Y-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 microCi. These mice displayed a significantly better (P < 0.01) antitumor response than control mice and survived >200 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine. Importantly, tumor-bearing mice treated with Y22 had no radiologic bone marrow damage compared with tumor-bearing mice treated with the control-labeled antibody arguing that the presence of CD22(+) tumor protected mice from bone marrow damage. When anti-CD22 radioimmunotherapy was compared to radioimmunotherapy with anti-CD19 and anti-CD45 antibodies, all three antibodies distributed significantly high levels of radioisotope to flank tumors in vivo compared with controls (P < 0.05), induced complete remission, and produced long-term, tumor-free survivors. These findings indicate that anti-CD22 radioimmunotherapy with Y22 is highly effective in vivo against CD22-expressing malignancies and may be a useful therapy for drug-refractory B cell leukemia patients.


Developmental shift of cyclophilin D contribution to hypoxic-ischemic brain injury.
Cyclophilin D (CypD), a regulator of the mitochondrial membrane permeability transition pore (PTP), enhances Ca(2+)-induced mitochondrial permeabilization and cell death in the brain. However, the role of CypD in hypoxic-ischemic (HI) brain injury at different developmental ages is unknown. At postnatal day (P) 9 or P60, littermates of CypD-deficient [knock-out (KO)], wild-type (WT), and heterozygous mice were subjected to HI, and brain injury was evaluated 7 d after HI. CypD deficiency resulted in a significant reduction of HI brain injury at P60 but worsened injury at P9. After HI, caspase-dependent and -independent cell death pathways were more induced in P9 CypD KO mice than in WT controls, and apoptotic activation was minimal at P60. The PTP had a considerably higher induction threshold and lower sensitivity to cyclosporin A in neonatal versus adult mice. On the contrary, Bax inhibition markedly reduced caspase activation and brain injury in immature mice but was ineffective in the adult brain. Our findings suggest that CypD/PTP is critical for the development of brain injury in the adult, whereas Bax-dependent mechanisms prevail in the immature brain. The role of CypD in HI shifts from a predominantly prosurvival protein in the immature to a cell death mediator in the adult brain.


Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat.
To investigate the potential protective effects of Tualang honey against the toxicity effects induced by Bisphenol A (BPA) on pubertal development of ovaries. This study was conducted on pre-pubertal female Sprague Dawley rats. Animals were divided into four groups (n = 8 in each group). Group I was administered with vehicle 0.2 ml of corn oil (Sigma-Aldrich, USA) using oral gavage daily for six weeks; these animals served as negative control (CO group), Group II was administered with BPA suspended in corn oil at 10 mg/kg body weight and served as positive control (PC group), Group III was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of BPA at 10 mg/kg (TH group) while Group IV was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of corn oil (THC group). Body weight of all animals were monitored weekly. The BPA-exposed animals exhibited disruption of their estrus cycle, while those animals treated with BPA together with Tualang honey, exhibited an improvement in percentage of normal estrous cycle. Their ovaries had lower numbers of atretic follicles compared to the PC group but higher than the CO group. Tualang honey has a potential role in reducing BPA-induced ovarian toxicity by reducing the morphological abnormalities of the ovarian follicles and improving the normal estrous cycle.


Southern Sudan: an opportunity for NTD control and elimination?
Southern Sudan has been ravaged by decades of conflict and is thought to have one of the highest burdens of neglected tropical diseases (NTDs) in the world. Health care delivery, including efforts to control or eliminate NTDs, is severely hampered by a lack of infrastructure and health systems. However, the post-conflict environment and Southern Sudan's emerging health sector provide the unprecedented opportunity to build new, innovative programmes to target NTDs. This article describes the current status of NTDs and their control in Southern Sudan and outlines the opportunities for the development of evidence-based, innovative implementation of NTD control.


Impact of uncertainty intolerance on clinical reasoning: A scoping review of the 21st-century literature.
RATIONALE, AIMS AND OBJECTIVES: Clinical reasoning is currently extensively studied to find out how to make proper diagnoses. Literature indicates that intolerance of uncertainty (IU) may have a strong negative impact on clinical reasoning. We summarize the various consequences of IU on clinical reasoning. A scoping review was conducted using relevant keywords to scientific databases (i.e., Google Scholar, Medline, PsycINFO and PBSC) from September to November 2021. Complementary research included relevant articles and articles retrieved through Google Scholar's alert system. We included articles about healthcare professionals as defined by the French Public Health Code (As defined here: https://www.vie-publique.fr/fiches/37855-categories-de-professionnels-de-sante-code-se-la-sante-publique), and articles reporting on the impact of IU or uncertainty management on clinical reasoning. We retrieved 1853 articles, of which 8 were kept for final analysis considering our inclusion criteria. Two behaviour categories were affected by uncertainty intolerance: investigative and prescriptive behaviours. Regarding the investigation process, mismanagement of uncertainty appeared to lead to reasoning bias, potentially resulting in diagnostic errors. IU was associated with withholding information, more referrals to peers and less use of new medical interventions. Regarding prescription behaviours, IU among health professionals could lead to overprescribing unnecessary or dangerous tests. IU was also associated with more antibiotic prescriptions for conditions where antibiotics are to be used carefully. Few studies have yet addressed the impact of IU on clinical reasoning. IU's influence is primarily observed on investigative and prescribing behaviours. More studies are needed to fully understand the impact of IU on clinical reasoning itself, and not only on practical consequences.


Effortless creation of safe robots from modules through self-programming and self-verification.
Industrial robots cannot be reconfigured to optimally fulfill a given task and often have to be caged to guarantee human safety. Consequently, production processes are meticulously planned so that they last for long periods to make automation affordable. However, the ongoing trend toward mass customization and small-scale manufacturing requires purchasing new robots on a regular basis to cope with frequently changing production. Modular robots are a natural answer: Robots composed of standardized modules can be easily reassembled for new tasks, can be quickly repaired by exchanging broken modules, and are cost-effective by mass-producing standard modules usable for a large variety of robot types. Despite these advantages, modular robots have not yet left research laboratories because an expert must reprogram each new robot after assembly, rendering reassembly impractical. This work presents our set of interconnectable modules (IMPROV), which programs and verifies the safety of assembled robots themselves. Experiments show that IMPROV robots retained the same control performance as nonmodular robots, despite their reconfigurability. With respect to human-robot coexistence, our user study shows a reduction of robot idle time by 36% without compromising on safety using our self-verification concept compared with current safety standards. We believe that by using self-programming and self-verification, modular robots can transform current automation practices.


Concurrent Validity of Equine Joint Range of Motion Measurement: A Novel Digital Goniometer versus Universal Goniometer.
Goniometry is the measurement of joint angles with a conventional universal goniometer (UG) or a digital goniometer (DG). The UG is validated for use in dogs and cats. However, it demands both of the user's hands when measuring. To avoid this, a novel type of DG has been developed, simplifying measurement by offering single-hand usage. The objective of this study is to examine the concurrent validity of the DG. The study consists of measurement with the DG and UG for flexion of the carpus and fetlock on ten horses, and with the DG in flexion and neutral positioning of the fetlock on a sedated horse and corresponding radiographs, intra- and inter-tester reliability and a survey on user-friendliness. The data were analyzed with ANOVA and intraclass correlation coefficient (ICC), with a significance of p < 0.05. The study showed significant differences in range of motion for the carpus and fetlock joint, a 2-3° difference comparing measurements on a sedated horse with corresponding radiographs, a "fair" to "excellent" inter-tester reliability and a "fair" to "almost perfect" intra-tester reliability, and the DG was easier to use than the UG. In conclusion, the novel DG may serve as a simple tool for measuring joint motion in equine rehabilitation patients.


Making stillbirths count, making numbers talk - issues in data collection for stillbirths.
Stillbirths need to count. They constitute the majority of the world's perinatal deaths and yet, they are largely invisible. Simply counting stillbirths is only the first step in analysis and prevention. From a public health perspective, there is a need for information on timing and circumstances of death, associated conditions and underlying causes, and availability and quality of care. This information will guide efforts to prevent stillbirths and improve quality of care. In this report, we assess how different definitions and limits in registration affect data capture, and we discuss the specific challenges of stillbirth registration, with emphasis on implementation. We identify what data need to be captured, we suggest a dataset to cover core needs in registration and analysis of the different categories of stillbirths with causes and quality indicators, and we illustrate the experience in stillbirth registration from different cultural settings. Finally, we point out gaps that need attention in the International Classification of Diseases and review the qualities of alternative systems that have been tested in low- and middle-income settings. Obtaining high-quality data will require consistent definitions for stillbirths, systematic population-based registration, better tools for surveys and verbal autopsies, capacity building and training in procedures to identify causes of death, locally adapted quality indicators, improved classification systems, and effective registration and reporting systems.