Information domain analysis of cardiovascular variability signals: evaluation of regularity, synchronisation and co-ordination.
A unifying general approach to measure regularity, synchronisation and co-ordination is proposed. This approach is based on conditional entropy and is specifically designed to deal with a small amount of data (a few hundred samples). Quantitative and reliable indexes of regularity, synchronisation and co-ordination (ranging from 0 to 1) are derived in a domain (i.e. the information domain) different from time and frequency domains. The method is applied to evaluate regularity, synchronisation and co-ordination among cardiovascular beat-to-beat variability signals during sympathetic activation induced by head-up tilt (T), during the perturbing action produced by controlled respiration at 10, 15 and 20 breaths/min (CR10, CR15 and CR20), and after peripheral muscarinic blockade provoked by the administration of low and high doses of atropine (LD and HD). It is found that: (1) regularity of the RR interval series is around 0.209; (2) this increases during T, CR10 and HD; (3) the systolic arterial pressure (SAP) series is more regular (0.406) and its regularity is not affected by the specified experimental conditions; (4) the muscle sympathetic (MS) series is a complex signal (0.093) and its regularity is not influenced by HD and LD; (5) the RR interval and SAP series are significantly, though weakly, synchronised (0.093) and their coupling increases during T, CR10 and CR15; (6) the RR interval and respiration are coupled (0.152) and their coupling increases during CR10; (7) SAP and respiration are significantly synchronised (0.108) and synchronisation increases during CR10; (8) MS and respiration are uncoupled and become coupled (0.119) after HD; (9) the RR interval, SAP and respiration are significantly co-ordinated (0.118) and co-ordination increases during CR10 and CR15; (10) during HD the co-ordination among SAP, MS and the respiratory signal is larger than that among the RR interval, SAP, MS and the respiratory signal, thus indicating that the RR interval contributes towards reducing co-ordination.


Asthma in Medicaid managed care enrollees residing in New York City: results from a post-World Trade Center disaster survey.
The collapse of the World Trade Center on September 11, 2001, released a substantial amount of respiratory irritants into the air. To assess the asthma status of Medicaid managed care enrollees who may have been exposed, the New York State Department of Health, Office of Managed Care, conducted a mail survey among enrollees residing in New York City. All enrollees, aged 5-56 with persistent asthma before September 11, 2001, were surveyed during summer 2002. Administrative health service utilization data from the Medicaid Encounter Data System were used to validate and supplement survey responses. A total of 3,664 enrollees responded. Multivariate logistic regression models were developed to examine factors associated with self-reported worsened asthma post September 11, 2001, and with emergency department/inpatient hospitalizations related to asthma from September 11, 2001, through December 31, 2001. Forty-five percent of survey respondents reported worsened asthma post 9/11. Respondents who reported worsened asthma were significantly more likely to have utilized health services for asthma than those who reported stable or improved asthma. Residence in both lower Manhattan (adjusted OR = 2.28) and Western Brooklyn (adjusted OR = 2.40) were associated with self-reported worsened asthma. However, only residents of Western Brooklyn had an elevated odds ratio for emergency department/inpatient hospitalizations with diagnoses of asthma post 9/11 (adjusted OR = 1.52). Worsened asthma was reported by a significant proportion of this low-income, largely minority population and was associated with the location of residence. Results from this study provide guidance to health care organizations in the development of plans to ensure the health of people with asthma during disaster situations.


Impact of litigation on senior clinicians: implications for risk management.
To investigate the impact of litigation on consultants and senior registrars and to establish their views on methods of reducing adverse events and litigation. Postal survey. Acute hospitals in the North Thames (West) Regional Health Authority. 1011 consultants and senior registrars in acute hospitals. Perceived causes and effects of adverse events; views on methods of reducing litigation and adverse events. 769 (76%) doctors responded. 288 (37%) had been involved in litigation at some point during their career; 213 surgeons (49%) and 75 (23%) doctors in the medical specialties. Anger, distress, and feeling personally attacked were common responses to litigation. Clinicians' views on reducing litigation emphasised the need for change at the clinical level. Supervision of junior staff, workload, and training in communication skills were to the fore. The high frequency of doctors who have experienced litigation and the emotional responses described indicate that clinicians require support at several levels. At a personal level, support can be offered to clinicians going through the litigation process or after an adverse event. Also, managerial support is needed by offering financial and practical help in correcting the factors that have been consistently identified as producing high risk situations to minimise the possibility of a reoccurrence. Accidents in medicine are, by their very nature, costly in human and financial terms and the root causes must be tackled. Recommendations are made for clinicians and risk management teams.


Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population.
Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.


Monitoring others' errors: The role of the motor system in early childhood and adulthood.
Previous research demonstrates that from early in life, our cortical sensorimotor areas are activated both when performing and when observing actions (mirroring). Recent findings suggest that the adult motor system is also involved in detecting others' rule violations. Yet, how this translates to everyday action errors (e.g., accidentally dropping something) and how error-sensitive motor activity for others' actions emerges are still unknown. In this study, we examined the role of the motor system in error monitoring. Participants observed successful and unsuccessful pincer grasp actions while their electroencephalography was registered. We tested infants (8- and 14-month-olds) at different stages of learning the pincer grasp and adults as advanced graspers. Power in Alpha- and Beta-frequencies was analysed to assess motor and visual processing. Adults showed enhanced motor activity when observing erroneous actions. However, neither 8- nor 14-month-olds displayed this error sensitivity, despite showing motor activity for both actions. All groups did show similar visual activity, that is more Alpha-suppression, when observing correct actions. Thus, while correct and erroneous actions were processed as visually distinct in all age groups, only the adults' motor system was sensitive to action correctness. Functionality of different brain oscillations in the development of error monitoring and mirroring is discussed.


Large field-induced strains in a lead-free piezoelectric material.
Piezoelectric materials exhibit a mechanical response to electrical inputs, as well as an electrical response to mechanical inputs, which makes them useful in sensors and actuators. Lead-based piezoelectrics demonstrate a large mechanical response, but they also pose a health risk. The ferroelectric BiFeO(3) is an attractive alternative because it is lead-free, and because strain can stabilize BiFeO(3) phases with a structure that resembles a morphotropic phase boundary. Here we report a reversible electric-field-induced strain of over 5% in BiFeO(3) films, together with a characterization of the origins of this effect. In situ transmission electron microscopy coupled with nanoscale electrical and mechanical probing shows that large strains result from moving the boundaries between tetragonal- and rhombohedral-like phases, which changes the phase stability of the mixture. These results demonstrate the potential of BiFeO(3) as a substitute for lead-based materials in future piezoelectric applications.


Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice.
Dopaminergic signaling plays an important role in associative learning, including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive one of the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct novel mechanisms by which mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1 receptors. Early extinction training augments both GABA co-release onto dorsomedial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.


[Counterpoint among personalities of the Brazilian Nursing Congresses and of the Revista Brasileira de Enfermagem from 1977 to 1987].
This is a qualitative study, using an exploratory approach, which has as its main aim to analyze and counterpoint central issues and personalities of the Brazilian Nursing Conferences and the editorials of the Brazilian Nursing Journal, from 1977 to 1987. It was analyzed 09 annuals and 24 editorials. The results show that the contents were aligned with the policy of the central ABEn. The leadership of Ana Nery School and USP Nursing School is evident in this period. Male nurses had no expressive participation in the nursing conferences, except those who were members of the PARTICIPACAO movement. We found only one editorial written by a male nurse. We observed changes in the central ABEn policy after 1984 provoked by the PARTICIPACAO movement and, influencing the change of subjects at the conferences, and the editorials of the REBEn.


A new familial sclerosing bone dysplasia.
Osteoscleroses are a heterogeneous group of bone remodeling disorders characterized by an increase in bone density. Here we report on a consanguineous Lebanese family in which two sisters, aged 39 and 36 years, exhibit a severe genu varum, a square-face appearance, high forehead, slight proptosis of the eyes, symmetric enlargement of the jaw, protruding chin, and short stature. Bone X-rays showed the presence of hyperostosis of the cranial base and vault with increased density of the orbits, hyperostosis of the bones, thickening of the cortices, diaphyseal modeling defects, cortical thickening of the medullary cavity, mild enlargement of the medullary cavity of the short long bones, short femoral necks, increased width of the ribs, and narrow interpedicular distances of the lower lumbar spine. Osteodensitometry showed values 200% to 300% above values for age. A cervical MRI revealed the presence of a diffuse osteosclerosis with calcification of the posterior vertebral ligament and a narrow canal between C2 and T2. Blood test results were unremarkable. Serum osteocalcin levels were in the normal range, whereas high values of serum C-telopeptide were noted. A bone biopsy showed only the presence of compact bone and did not allow for histomorphometric analysis. Molecular studies excluded genes known to be involved in sclerosing bone dysplasias as the cause of this condition. In vitro analysis of osteoclast function indicated that contrary to most cases of autosomal recessive osteopetrosis, osteoclasts both formed and resorbed but exhibited a small decrease in resorptive activity compared with osteoclasts generated from normal control individuals. Differential diagnoses are discussed, and the possibility that this may be a novel clinical entity is raised.


Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex.
Gram-negative bacteria use specific heme uptake systems, relying on outer membrane receptors and excreted heme-binding proteins (hemophores) to scavenge and actively transport heme. To unravel the unknown molecular details involved, we present 3 structures of the Serratia marcescens receptor HasR in complex with its hemophore HasA. The transfer of heme over a distance of 9 A from its high-affinity site in HasA into a site of lower affinity in HasR is coupled with the exergonic complex formation of the 2 proteins. Upon docking to the receptor, 1 of the 2 axial heme coordinations of the hemophore is initially broken, but the position and orientation of the heme is preserved. Subsequently, steric displacement of heme by a receptor residue ruptures the other axial coordination, leading to heme transfer into the receptor.


Fast neuromorphic sound localization for binaural hearing aids.
We report on the neuromorphic sound localization circuit which can enhance the perceptual sensation in a hearing aid system. All elements are simple leaky integrate-and-fire neuron circuits with different parameters optimized to suppress the impacts of synaptic circuit noises. The detection range and resolution of the proposed neuromorphic circuit are 500 us and 5 us, respectively. Our results show that, the proposed technique can localize a sound pulse with extremely narrow duration (∼ 1 ms) resulting in real-time response.


Cost-effectiveness profiles with an expanding treatment population.
In trying to identify the therapeutic impact of a drug, clinical trials eliminate potentially confounding factors such as comorbidities, poor compliance and treatment errors in diagnosis, dosing, and drug interactions. Elimination of these variables means that attempts to use clinical data as the basis for predicting relative cost-effectiveness are fraught with difficulties. In this article a theoretical framework is proposed, which, for a single drug intervention, examines the relationship between assumed patterns of clinical effectiveness, costs of drug delivery, and the proportion of the prospective patient population being treated. Cost-effectiveness profiles are generated to represent both usual-treatment situations and situations where interventions to reduce misdiagnoses, adverse events, and noncompliance attempt to push clinical effectiveness to a maximum (given the existence of comorbidities). Without data describing effectiveness and cost profiles, and unless strict assumptions are made as to effectiveness and cost functions, profiles of cost-effectiveness cannot be predicted.


The Impact of High-Temperature Superconductivity on SQUID Magnetometers.
DC and RF Superconducting QUantum Interference Devices (SQUIDs) fabricated from low transition temperature (T(c)) superconductors and operated at liquid (4)He temperatures are routinely used as ultrasensitive detectors in many applications, for example, as magnetometers, magnetic gradiometers, voltmeters, and motion detectors. SQUIDs fabricated from high T(c) superconductors such as YBa(2)Cu(3)O(7) and operated in liquid nitrogen at 77 K offer a greater convenience in operation at the expense of a poorer noise performance, particularly at low frequencies. The resolution of SQUID-based magnetometers is compared with that of other types of magnetometers operatng at ambient temperatures.


A new basal subfamily of mariner elements in Ceratitis rosa and other tephritid flies.
Several copies of highly related transposable elements, Crmar2, Almar1, and Asmar1, are described from the genomes of Ceratitis rosa, Anastrepha ludens, and A. suspensa, respectively. One copy from C. rosa, Crmar2.5, contains a full-length, uninterrupted ORF. All the other copies, from the three species contain a long deletion within the putative ORF. The consensus Crmar2 element has features typical of the mariner/Tc1 superfamily of transposable elements. In particular, the Crmar2 consensus encodes a D,D41D motif, a variant of the D,D34D catalytic domain of mariner elements. Phylogenetic analysis of the relationships of these three elements and other members of the mariner/Tc1 superfamily, based on their encoded amino acid sequences, suggests that they form a new basal subfamily of mariner elements, the rosa subfamily. BLAST analyses identified sequences from other diptera, including Drosophila melanogaster, which appear to be members of the rosa subfamily of mariner elements. Analyses of their molecular evolution suggests that Crmar2 entered the genome of C. rosa in the recent past, a consequence of horizontal transfer.


Outcome of Appendicectomies at Surgery for Mucinous Ovarian Neoplasms: Report From A UK Center and Review of Literature.
This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT). Women with borderline and malignant MOT were identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study. Data were collected from the electronic patient record and case notes. Of 310 women identified with MOT, 203 patients with benign MOT were excluded. Of the remaining 107 patients, 15 patients with previous appendicectomy were also excluded. The study population consisted of 92 patients. There were 57 (62%) patients with borderline MOT and 35 (38%) patients with malignant MOT. In the borderline subgroup, 40/57 (70%) patients had appendicectomy of whom 8 (20%) had macroscopically abnormal appendices. One patient had pseudomyxoma peritonei secondarily involving the appendix and 7 patients had a histologically normal appendix. Normal histology was found in all macroscopically normal appendices. In the malignant subgroup, 29/35 (83%) patients had an appendicectomy. There were 8 (27.5%) macroscopically abnormal appendices with a malignant pathology in 7 (87.5%) patients and 1 patient had a resolving appendicitis. There were 21 macroscopically normal appendices of which, serrated adenoma was found in 1 (4.8%) patient, whereas the remaining 20 (95.2%) patients had normal histology. In MOT, an abnormal appearing appendix should be excised. If the appendix is grossly normal, our data do not support performing an appendicectomy as part of a surgical staging procedure.


Experimental demonstration of the utility of pressure sensitivity kernels in time-reversal.
Pressure sensitivity kernels were recently applied to time-reversal acoustics in an attempt to explain the enhanced stability of the time-reversal focal spot [Raghukumar et al., J. Acoust. Soc. Am. 124, 98-112 (2008)]. The theoretical framework developed was also used to derive optimized source functions, closely related to the inverse filter. The use of these optimized source functions results in an inverse filter-like focal spot which is more robust to medium sound speed fluctuations than both time-reversal and the inverse filter. In this paper the theory is applied to experimental data gathered during the Focused Acoustic Fields experiment, conducted in 2005, north of Elba Island in Italy. Sensitivity kernels are calculated using a range-independent sound-speed profile, for a geometry identical to that used in the experiment, and path sensitivities are identified with observed arrivals. The validity of the kernels in tracking time-evolving Green's functions is studied, along with limitations that result from a linearized analysis. An internal wave model is used to generate an ensemble of sound speed profiles, which are then used along with the calculated sensitivity kernels to derive optimized source functions. Focal spots obtained using the observed Green's functions with these optimized source functions are then compared to those obtained using time-reversal and the inverse-filter. It is shown that these functions are able to provide a focal spot superior to time-reversal while being more robust to sound speed fluctuations than the inverse filter or time-reversal.


Rehabilitation at the Time of Pandemic: Patient Journey Recommendations.
The World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic in March 2020, causing almost 3.5 million coronavirus disease (COVID-19) related deaths worldwide. The COVID-19 pandemic has imposed a significant burden on healthcare systems, economies, and social systems in many countries around the world. The access and delivery of rehabilitation care were severely disrupted, and patients have faced several challenges during the COVID-19 outbreak. These challenges include addressing new functional impairments faced by survivors of COVID-19 and infection prevention to avoid the virus spread to healthcare workers and other patients not infected with COVID-19. In this scoping review, we aim to develop rehabilitation recommendations during the COVID-19 pandemic across the continuum of rehabilitation care. Established frameworks were used to guide the scoping review methodology. Medline, Embase, Pubmed, CINAHL databases from inception to August 1, 2020, and prominent rehabilitation organizations' websites were searched. We included articles and reports if they were focused on rehabilitation recommendations for COVID-19 survivors or the general population at the time of the COVID-19 pandemic. Two of our team members used the pre-tested data extraction form to extract data from included full-text articles. The strength and the quality of the extracted recommendations were evaluated by two reviewers using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. We retrieved 6,468 citations, of which 2,086 were eligible after removing duplicates. We excluded 1,980 citations based on the title and the abstract. Of the screened full-text articles, we included 106 studies. We present recommendations based on the patient journey at the time of the pandemic. We assessed the evidence to be of overall fair quality and strong for the recommendations. We have combined the latest research results and accumulated expert opinions on rehabilitation to develop acute and post-acute rehabilitation recommendations in response to the global COVID-19 pandemic. Further updates are warranted in order to incorporate the emerging evidence into rehabilitation guidelines.


Different types of calcium channels.
Ca2+ channels allow passage of Ca2+ ions into the cytoplasm through a selective pore which is opened in response to depolarization of the cell membrane (for reviews see Hagiwara & Byerly, 1981, 1983; Tsien, 1983; Reuter, 1983). The Ca2+ flux creates a net inward, depolarizing current and the resulting accumulation of Ca2+ in the cytoplasm can act as a chemical trigger for secretion of hormones and neurotransmitters, contraction of muscle and a variety of other Ca2+-sensitive events. Thus, upon sensing membrane potential changes, Ca2+ channels simultaneously generate an electrical signal while directly creating an intracellular chemical messenger. This dual ability is unique among the family of ion channels and allows the Ca2+ channel to play a variety of roles in excitation-secretion and excitation-contraction coupling. It has now become clear that versatility of function is reflected by diversity of the types of Ca2+ channels on the membrane of individual cells. This article describes the nature of data which have demonstrated multiple channel types, reviews the literature suggesting that many cells have several kinds of Ca2+ channels, and discusses newer data regarding a neurotoxin that distinguishes among different Ca2+ channels.


FLT3 and JAK2 Mutations in Acute Myeloid Leukemia Promote Interchromosomal Homologous Recombination and the Potential for Copy Neutral Loss of Heterozygosity.
Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N-acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR.


New mastitis phenotypes suitable for genomic selection in meat sheep and their genetic relationships with udder conformation and lamb live weights.
Mastitis can prove expensive in sheep reared for meat production due to costs associated with treatment methods, poor lamb growth and premature culling of ewes. The most commonly used method to detect mastitis, in dairy systems, is somatic cell counts. However, in many meat-producing sheep flocks ewes are not routinely handled, thus regular milk sampling is not always possible. It is, therefore, worthwhile to investigate alternative phenotypes, such as those associated with udder conformation and methods of evaluating somatic cell counts in the milk, such as the California Mastitis Test. The main objectives of this study were therefore: (a) to estimate genetic parameters of traits relating to mastitis and udder conformation in a meat sheep breed; (b) estimate the level of association between somatic cell counts and the California Mastitis Test and (c) assess the relationships between mastitis and both udder conformation and lamb live weights. Data were collected from Texel ewes based on 29 flocks, throughout the UK, during 2015 and 2016. The ewes were scored twice each year, at mid- and late-lactation. Eight different conformation traits, relating to udder and teat characteristics, and milk samples were recorded. The data set comprised of data available for 2957 ewes. The pedigree file used contained sire and dam information for 31 775 individuals. The animal models used fitted relevant fixed and random effects. Heritability estimates for traits relating to mastitis (somatic cell score and the California Mastitis Test), ranged from 0.08 to 0.11 and 0.07 to 0.11, respectively. High genetic correlations were observed between somatic cell score and the California Mastitis Test (0.76 to 0.98), indicating the California Mastitis Test to be worthwhile for assessing infection levels, particularly at mid-lactation. The strongest correlations observed between the mastitis traits and the udder conformation traits were associated with udder depth (0.61 to 0.75) also at mid-lactation. Negative phenotypic correlations were estimated between mastitis and the weight of lamb reared by the ewe (-0.15 to -0.23), suggesting that lamb weights fell as infection levels rose. Genetic correlations were not significantly different from zero. Reducing mastitis will lead to improvements in flock productivity and the health and welfare of the animals. It will also improve the efficiency of production and the resilience to disease challenge. The economic benefits, therefore, of these results combined could be substantial not only in this breed but also in the overall meat sheep industry.


Classification of Tattoo Complications in a Hospital Material of 493 Adverse Events.
Tattooing is a global trend. Clinical knowledge of complications is based on case reports collected over a century. Larger cohorts reflecting complications associated with contemporary trends are lacking. The study was a retrospective review of a consecutive cohort of patients with tattoo complications diagnosed in the "Tattoo Clinic" of Bispebjerg University Hospital in Copenhagen, Denmark, from 2008 to 2015, based on patient history and systematic clinical examination. A total of 493 tattoo complications in 405 patients were studied. Overall, 184 (37%) presented allergic reactions with plaque elevation in 32.2%, excessive hyperkeratosis in 3.7%, and ulceration in 1.4%, predominantly observed in red tattoos and nuances of red; 66 (13%) presented papulo-nodular reactions, mainly observed in black tattoos (considered non-allergic) and due to pigment agglomeration; 53 (11%) had bacterial infections; 46 (9%) were psycho-social complications; 144 (30%) belonged to several specific diagnostic entities, including photosensitivity, pain syndrome, and lymphopathy. We found no cases of cutaneous or other malignancies. Sarcoidosis was primarily seen in black tattoos and was a common associated disease, found in 23 reactions (5%), compared to the background population. The study introduces a new concept of classification of tattoo complications based on simple tools such as patient history and objective findings supplemented with histology. The study reflects complications originating from presently used tattoo inks, often with organic pigments. The introduced classification has been submitted to the World Health Organisation (WHO) as a proposal to the 11th revision of the International Classification of Diseases.


Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial.
Renal cell cancer and malignant melanoma are two types of cancer that are responsive to immunotherapy. In this phase I dose-escalation study, the feasibility of large-scale expansion and safety of administering ex vivo-expanded NK-92 cells as allogeneic cellular immunotherapy in patients with refractory renal cell cancer and melanoma were determined. Twelve patients (aged 31-74 years) were enrolled, three per cohort at cell dose levels of 1x10(8)/m(2), 3x10(8)/m(2), 1x10(9)/m(2) and 3x10(9)/m(2). One treatment course consisted of three infusions. Eleven patients had refractory metastatic renal cell cancer; one patient had refractory metastatic melanoma. The NK-92 cells were expanded in X-Vivo 10 serum-free media supplemented with 500 U/mL Proleukin recombinant human interleukin-2 (rhIL-2), amino acids and 2.5% human AB plasma. Final yields of approximately 1x10(9) cells/culture bag (218-250xexpansion) over 15-17 days were achievable with >or=80% viability. Infusional toxicities of NK-92 were generally mild, with only one grade 3 fever and one grade 4 hypoglycemic episode. All toxicities were transient, resolved and did not require discontinuation of treatment. One patient was alive with disease at 4 years post-NK-92 infusion. The one metastatic melanoma patient had a minor response during the study period. One other patient exhibited a mixed response. This study establishes the feasibility of large-scale expansion and safety of administering NK-92 cells as allogeneic cellular immunotherapy in advanced cancer patients and serves as a platform for future study of this novel natural killer (NK)-cell based therapy.


A preliminary study on pressure-plate evaluation of forelimb toe-heel and mediolateral hoof balance on a hard vs. a soft surface in sound ponies at the walk and trot.
Thus far, pressure-plate analysis has been limited to measurements on a hard surface, whereas equine athletes routinely perform on a deformable substrate. To explore pressure-plate analysis on arena footing. Nonrandomised crossover study using noninvasive techniques. Five sound, unshod ponies were walked and trotted over a pressure plate in 2 different conditions. In the first session, the plate was covered with only a 5 mm rubber mat, and in the second session, with an additional 50 mm layer of sand and synthetic fibres. Limb loading and timing variables (peak vertical force, vertical impulse, peak vertical pressure, hoof contact area and stance phase duration) were obtained. Toe-heel and mediolateral hoof balance of the vertical force were calculated throughout stance (126 Hz). Peak vertical force, vertical impulse, peak vertical pressure and stance phase duration were decreased on the soft substrate, while hoof contact area increased. At impact, there was more even load distribution between the toe and heel region on the soft vs. hard surface. At mid-stance, there was more loading of the toe region on the soft compared with the hard surface. At impact, there was more even load distribution between lateral and medial on the soft vs. hard surface at walk, but not at trot. Comparison of observed vs. expected impulse indicated that the main factor involved in the lower loading on the soft surface is the dampening effect of the soft substrate, although definitive conclusions require concurrent force-plate analysis. The pressure plate permitted quantitative evaluation of hoof balance of the vertical force on a deformable surface at the walk and trot and proved that there is more even load distribution on arena footing.


Occurrence and infection risk of waterborne pathogens in Wanzhou watershed of the Three Gorges Reservoir, China.
The Three Gorges Reservoir (TGR), formed by China's Yangtze Three Gorges Project, is the largest lake in the world, but there is too little information available about fecal contamination and waterborne pathogen impacts on this aquatic ecosystem. During two successive 1-year study periods (July 2009 to July 2011), the water quality in Wanzhou watershed of the TGR was tested with regard to the presence of fecal indicators and pathogens. According to Chinese and World Health Organization water quality standards, water quality in the mainstream was good but poor in backwater areas. Salmonella, Enterohemorrhagic Escherichia coli (EHEC), Giardia and Cryptosporidium were detected in the watershed. Prevalence and concentrations of the pathogens in the mainstream were lower than those in backwater areas. The estimated risk of infection with Salmonella, EHEC, Cryptosporidium, and Giardia per exposure event ranged from 2.9 x 10(-7) to 1.68 x 10(-5), 7.04 x 10(-10) to 2.36 x 10(-7), 5.39 x 10(-6) to 1.25 x 10(-4) and 0 to 1.2 x 10(-3), respectively, for occupational divers and recreational swimmers exposed to the waters. The estimated risk of infection at exposure to the 95% upper confidence limit concentrations of Salmonella, Cryptosporidium and Giardia may be up to 2.62 x 10(-5), 2.55 x 10(-4) and 2.86 x 10(-3), respectively. This study provides useful information for the residents, health care workers and managers to improve the safety of surface water and reduce the risk of fecal contamination in the TGR.


Metformin in cancer prevention and therapy.
The prevalence of diabetes is dramatically increasing worldwide. The results of numerous epidemiological studies indicate that diabetic population is not only at increased risk of cardiovascular complications, but also at substantially higher risk of many forms of malignancies. The use of metformin, the most commonly prescribed drug for type 2 diabetes, was repeatedly associated with the decreased risk of the occurrence of various types of cancers, especially of pancreas and colon and hepatocellular carcinoma. This observation was also confirmed by the results of numerous meta-analyses. There are however, several unanswered questions regarding the exact mechanism of the anticancer effect of metformin as well as its activity against various types of cancer both in diabetic and nondiabetic populations. In the present work we discuss the proposed mechanism(s) of anticancer effect of metformin and preclinical and clinical data suggesting its anticancer effect in different populations.


Health policy and the politics of research in the United States.
During the past decade research has been more important to the health policy-making process in the United States than at any time in the past. This article describes and assesses three competing normative models for research on health affairs: economizing, social conflict, and collective welfare. The three models provide a context for the history of research bearing on health policy in the past half century, with particular pertinence to the years since 1980. The article concludes with a discussion of some of the consequences of the new legitimacy of research.


Macro and microfluidic flows for skeletal regenerative medicine.
Fluid flow has a great potential as a cell stimulatory tool for skeletal regenerative medicine, because fluid flow-induced bone cell mechanotransduction in vivo plays a critical role in maintaining healthy bone homeostasis. Applications of fluid flow for skeletal regenerative medicine are reviewed at macro and microscale. Macroflow in two dimensions (2D), in which flow velocity varies along the normal direction to the flow, has explored molecular mechanisms of bone forming cell mechanotransduction responsible for flow-regulated differentiation, mineralized matrix deposition, and stem cell osteogenesis. Though 2D flow set-ups are useful for mechanistic studies due to easiness in in situ and post-flow assays, engineering skeletal tissue constructs should involve three dimensional (3D) flows, e.g., flow through porous scaffolds. Skeletal tissue engineering using 3D flows has produced promising outcomes, but 3D flow conditions (e.g., shear stress vs. chemotransport) and scaffold characteristics should further be tailored. Ideally, data gained from 2D flows may be utilized to engineer improved 3D bone tissue constructs. Recent microfluidics approaches suggest a strong potential to mimic in vivo microscale interstitial flows in bone. Though there have been few microfluidics studies on bone cells, it was demonstrated that microfluidic platform can be used to conduct high throughput screening of bone cell mechanotransduction behavior under biomimicking flow conditions.


Adolescent mothers' breastfeeding social support needs.
To define aspects of social support that adolescents need from nurses when initiating breastfeeding in the early postpartum. MEDLINE and CINAHL databases for years 2000 to 2009. Three searches were done using the following subject terms: adolescent mothers and breastfeeding (12 studies), adolescent mothers and breastfeeding and support (24 studies), and breastfeeding and adolescent mothers and attitudes (15 studies). The 18 studies that were chosen for this synthesized review illuminated the dimensions of social support identified by House. The four types of supportive behavior categories identified by House were described in these studies (informational, instrumental, emotional, and appraisal). Esteem support as defined by Sarafino seemed to be synonymous with appraisal support. Many studies identified the importance of network support as a fifth category of supportive behavior in increased breastfeeding duration among adolescents; network support was included in this synthesis. These five types of social support provide a framework for defining supportive nurse behaviors. Nurses in the early postpartum can promote the long-term health of adolescents and their children through the social support they offer adolescent mothers as they initiate breastfeeding. Network support appears to be essential to adolescents' breastfeeding experiences and needs to be included with informational, instrumental, emotional, and esteem/appraisal support when investigating support for this population. By integrating the five dimensions of social support into their care, nurses play an essential role in providing adolescents with the positive experiences that are so important to establishing breastfeeding.


Evaluation of remaining dentin thickness and fracture resistance of conventional and conservative access and biomechanical preparation in molars using cone-beam computed tomography: An in vitro study.
The present study aimed to compare the remaining dentin thickness (RDT) and fracture resistance of conventional and conservative access and biomechanical preparation in molars using cone-beam computed tomography (CBCT). A total of 60 freshly extracted human molars were selected and were randomly divided into two groups of conventional and conservative access preparation group (n = 30). Samples were subjected to pre-CBCT scan at the pericervical region for the measurement of total dentin thickness. For the conventional group, samples were accessed and biomechanical preparation was done using K3 XF file. For conservative group, samples were accessed using CK microendodontic burs using a dental operating microscope and biomechanical preparation was done using self-adjusting file. After obturation and postobturation with nanohybrid composite restoration, samples of both groups were subjected to post-CBCT scan at pericervical region for the measurement of RDT. The samples were then loaded to fracture in the Instron Universal Testing Machine, and the data were analyzed using paired sample t-test and independent sample t-test. The mean RDT was less in conventional group than conservative group. Pericervical dentin was preserved more in conservative group. The statistical difference among both the experimental group was highly significant (<0.001). The mean load at fracture was less in conventional group than conservative group (<0.001). Coronal dentin was conserved in molars when accessed through conservative than through conventional. The dentin conservation afforded an increased resistance to fracture in conservative group which is doubled the fracture resistance in conventional group.


Associations between forest characteristics and socio-economic development: a case study from Portugal.
The integration of socio-economic and environmental objectives is a major challenge in developing strategies for sustainable landscapes. We investigated associations between socio-economic variables, landscape metrics and measures of forest condition in the context of Portugal. The main goals of the study were to 1) investigate relationships between forest conditions and measures of socio-economic development at national and regional scales, 2) test the hypothesis that a systematic variation in forest landscape metrics occurs according to the stage of socio-economic development and, 3) assess the extent to which landscape metrics can inform strategies to enhance forest sustainability. A ranking approach and statistical techniques such as Principal Component Analysis were used to achieve these objectives. Relationships between socio-economic characteristics, landscape metrics and measures of forest condition were only significant in the regional analysis of municipalities in Northern Portugal. Landscape metrics for different tree species displayed significant variations across socio-economic groups of municipalities and these differences were consistent with changes in characteristics suggested by the forest transition model. The use of metrics also helped inform place-specific strategies to improve forest management, though it was also apparent that further work was required to better incorporate differences in forest functions into sustainability planning.


SU-E-T-318: Source Position Localization for ICBT Tandem & Ovoid Applicators Utilizing Oncentra Brachy Applicator Modeling.
Nucletron's Oncentra Brachy Applicator Modeling plugin (AMp) may facilitate HDR cervical brachytherapy treatment planning when image artifact inhibits dwell position localization. The AMp utilizes a 3D CAD rendering of the corresponding applicator to define possible source dwell positions. This study compares the equivalence of source localization within a CT/MR Fletcher-type tandem and ovoid applicator utilizing clinical practice and Oncentra's AMp in a water phantom containing OAR surrogate structures. KVCT image sets were acquired of a water phantom containing bladder and rectum surrogates as well as an assembled Nucletron Fletcher CT/MR applicator with various ovoid sizes (20, 25, 30mm) and a 30° tandem. Using Oncentra's Brachy TPS, OAR-surrogates were segmented and catheters were reconstructed using (1) clinical protocols (i.e. using source dwell position markers) and (2) using the AMp. Treatment plans were generated following clinical protocol, ensuring 600cGy to the ICRU 38-defined Point A. The center coordinates of each active dwell position were spatially compared. The dosimetric impact of these differences was quantified by determining D0. 1cc, D1cc and D2cc for the surrogate OARs. Preliminary results obtained for the 25mm ovoid / 30° tandem applicator show 80% of dwell positions defined by clinical protocol and the AMp agree within 1mm with a maximum deviation of 1.17mm. Differences in source positions resulted in an increase of 2.9%, 0.48% and 0.3% and 0.66%, 0.87%, and 0.59% for D0.1cc, D1cc and D2cc for the bladder- and rectum-surrogates, respectively, when utilizing the AMp rather than clinical protocol for source position localization. Preliminary results indicate that source dwell position localization utilizing Nucletron's Applicator Modeling plugin and our clinical protocol results in equivalent dosimetry for the simple, water phantom geometry investigated. Currently we are investigating the validity of this conclusion utilizing ovoids of different sizes as well as a CT/MR-compatible vaginal cylinder.


Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE (Q-soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor) protein syntaxin 6.
PDZ domains are involved in the scaffolding and assembly of multi-protein complexes at various subcellular sites. We describe here the isolation and characterization of a novel PDZ domain-containing protein that localizes to the Golgi apparatus. Using an in silico cloning approach, we have identified and isolated a cDNA encoding a ubiquitously expressed 59-kDa protein that we call FIG. It is composed of two coiled coil regions, a leucine zipper, and a single PDZ domain. Cytological studies using indirect immunofluorescence microscopy revealed that FIG is a peripheral protein that uses one of its coiled coil domains to localize to the Golgi apparatus. To ascertain the modalities of this Golgi localization, the same coiled coil region was tested for its ability to interact with a panel of coiled coil domain-containing integral membrane Golgi proteins. Using a series of GST fusion protein binding assays, co-immunofluorescence and co-immunoprecipitation experiments, we show that FIG specifically binds to the coiled coil domain-containing Q-SNARE (Q-soluble NSF attachment protein receptor) protein syntaxin 6 both in vitro and in vivo. The structural features of FIG and its interaction with a SNARE protein suggest that FIG may play a role in membrane vesicle trafficking. This is the first example of a PDZ domain-containing peripheral protein that localizes to the Golgi through a coiled coil-mediated interaction with a resident membrane protein. Our results broaden the scope of PDZ domain-mediated functions.


Effects of arthroscopic meniscectomy on the long-term prognosis for the discoid lateral meniscus.
This study compared the long-term clinical and radiological outcomes, according to the extent of arthroscopic meniscectomy, of complete and incomplete types of the discoid lateral meniscus. A total of 125 discoid menisci (74 complete and 51 incomplete types) without significant cartilage erosion at the time of surgery were included. The extent of meniscectomy was decided along with tear patterns and the stability of the discoid meniscus. Both clinical and radiological results were evaluated after total or partial meniscectomy. In the complete type of discoid meniscus with less than 5 years of follow-up, the total meniscectomy group showed better clinical results than the partial meniscectomy group. However, with over 5 years of follow-up, there were no differences between the two groups. In the radiological results, there was no significant difference between the two groups during the first 5 years after operation. However, with more than 5 years of follow-up, the partial meniscectomy group showed better results than the total meniscectomy group. In the incomplete-type discoid meniscus, clinical results were better in the partial meniscectomy group regardless of the follow-up periods. In the radiological results, the partial meniscectomy group showed better results for only more than 5 years of follow-up. The long-term prognosis after arthroscopic meniscectomy for the torn discoid lateral meniscus was related to the volume of the meniscus removed.


Integrative Approaches for microRNA Target Prediction: Combining Sequence Information and the Paired mRNA and miRNA Expression Profiles.
Gene regulation is a key factor in gaining a full understanding of molecular biology. microRNA (miRNA), a novel class of non-coding RNA, has recently been found to be one crucial class of post-transactional regulators, and play important roles in cancer. One essential step to understand the regulatory effect of miRNAs is the reliable prediction of their target mRNAs. Typically, the predictions are solely based on the sequence information, which unavoidably have high false detection rates. Recently, some novel approaches are developed to predict miRNA targets by integrating the typical algorithm with the paired expression profiles of miRNA and mRNA. Here we review and discuss these integrative approaches and propose a new algorithm called HCTarget. Applying HCtarget to the expression data in multiple myeloma, we predict target genes for ten specific miRNAs. The experimental verification and a loss of function study validate our predictions. Therefore, the integrative approach is a reliable and effective way to predict miRNA targets, and could improve our comprehensive understanding of gene regulation.


Inconsolable night-time awakening: beyond night terrors.
Sophia is a 3-year-old girl who was brought to her pediatrician by her parents who were concerned about inconsolable night-time awakening. Her mother indicated that she has frequent (>6), early nocturnal awakenings accompanied by screaming and crying lasting up to 1 hour since her birth. These episodes increased in intensity and frequency in the past year since the birth of her brother. With a bedtime routine (a cup of water by bedside with a washcloth and touching mother's nose, chin, and cheeks), Sophia falls asleep easily; however, within 1 hour she awakes screaming and flailing unaware of her surroundings and unable to be comforted. There are no tonic-clonic movements. Prior interventions, including a sleep coach and "letting Sophia cry it out," did not change her sleep pattern. Sophia's mother reports that she needs to be on a specific daily routine including set times for awakening, activity, snacks, naps, and meals. Diversion from the routine and separation from her mother results in a tantrum (kicking, hitting, screaming, and inconsolability) often lasting more than 30 minutes. Sophia was born after an uncomplicated 37-week gestation. Neonatal hyperbilirubinemia required readmission for 24 hours of phototherapy; serum bilirubin levels were performed daily for 3 weeks after discharge. At 6 weeks, daily episodes of screaming, inconsolability, forceful vomiting, and inability to sleep led to a diagnosis of gastroesophageal reflux. Medication trials were not successful, but the symptoms resolved by 5 months. Formula intolerance and difficulty swallowing and chewing different textures of solid food occurred in the first year. Occupational therapy was of "no benefit"; Sophia was overwhelmed by the activity and took a long time to warm up to the therapist. Her texture aversion resolved by 2 years of age. She prefers one-on-one play and has minimal interactions with other children. She has met all her developmental milestones appropriately and has no other health issues. Sophia lives with her parents and infant brother. There is a maternal family history of insomnia and sleep walking and a paternal history of sleep walking. Her mother adheres to a strict daily schedule. Sleep deprivation, different parental child-rearing practices, social isolation, and lack of quality parent time were all identified by the mother as significant marital stressors. During the office visit, Sophia required 30 minutes to warm up and smile, and over 60 minutes before she spoke her first word. Physical examination was normal (including growth measurements) and the developmental examination was age-appropriate. Upon completion of the assessment, she was engaging, playful, and cooperative with the pediatrician.


New partnerships, new perspectives: The relevance of sexual and reproductive health and rights for sustainable development.
In the light of the opportunities presented by the Sustainable Development Goals (SDGs) debate is being reignited to understand the connections between human population dynamics (including rapid population growth) and sustainable development. Sustainable development is seriously affected by human population dynamics yet programme planners too often fail to consider them in development programming, casting doubt on the sustainability of such programming. Some innovative initiatives are attempting to cross sector boundaries once again, such as the Population Health and Environment (PHE) programmes, which are integrated programmes encompassing family planning service provision with broader public health services and environmental conservation activities. These initiatives take on greater prominence in the context of the SDGs since they explicitly seek to provide cross-sector programming and governance to improve both human and planetary wellbeing. Yet such initiatives remain under-researched and under promoted.


Efficacy of high dose Vitamin D supplementation in improving serum 25(OH)D among migrant and non migrant population: a retrospective study.
Higher dose of vitamin D supplementation 50000 IU is required for those whose serum 25(OH)D levels are 50 nmol/L and below. The increment in serum 25(OH)D though not significantly affected by race, sex or age it is negatively correlated to the baseline 25(OH)D concentration. This study investigated whether the mean increase in serum 25(OH)D will be higher among participants with lower baseline 25(OH)D levels and whether the duration of supplementation has an influence on the serum 25(OH)D achieved. A clinical audit of patients' medical records from a community health centre in Melbourne for the period 01.01.2010 to 31-12.2012 was undertaken. Paired sample t test was used to determine difference in pre and post dose serum 25(OH)D. Simple and multiple linear regressions were used to examine the association between the difference in pre and post dose serum 25(OH)D and duration of supplementation and baseline serum 25(OH)D, adjusting for socio-demographic factors. A total of 205 patients were included in the study. Mean difference in serum 25(OH)D was highest 52.8 nmol/L (95 % CI: 46.63-58.92) among those whose serum 25(OH)D was below 25 nmol/L at baseline. Baseline 25(OH)D alone accounted for 13.7 % of variance in the effect size (F(2, 202) = 16.0. p < 0.001), with the effect size significantly higher among participants with a baseline 25(OH)D level of 25-49 nmol/L (β = 11.93, 95 % CI: 0.48, 23.40, p < 0.05). Mean serum 25(OH)D difference was highest, 47.53 nmol/L (95 % CI: 40.95-54.11) when measured within 3 months of supplementation. Duration of supplementation explained 2.9 % of the variance in the effect size (F (1, 203) = 6.11, p < 0.05) and there was an inverse relationship between the length of supplementation and mean pre and post supplementation serum 25(OH)D difference (β = -1.45, 95 % CI: -2.62, -0.29, p = 0.014). Following 50000 IU vitamin D3 for 12 months mean serum 25(OH)D increase was highest among those whose baseline serum 25(OH)D was lower. Migrants especially dark-skinned are at a high risk for vitamin D deficiency in Australia. High dose vitamin D3 50000 IU (cholecalciferol) is effective in achieving sufficient serum 25(OH)D among these populations who tend to have lower baseline serum 25(OH)D.


Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline.
Optimum management to prevent recurrent kidney stones is uncertain. To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. Agency for Healthcare Research and Quality.


Body Mass Index Can Increase the Risk of Gallbladder Cancer: A Meta-Analysis of 14 Cohort Studies.
BACKGROUND This study sought to appraise the association between raised body mass index (BMI) and the risk of gallbladder cancer (GBC) by performing a meta-analysis of 14 cohort studies. MATERIAL AND METHODS Eligible cohort studies were selected by searching PubMed and EMBASE from their inception to May 26, 2016, and the reference lists of retrieved articles were also consulted. The information was screened by two authors separately. We used a fixed-effects model to calculate the overall pooled risk estimates. A random-effects model was used to identify heterogeneity. RESULTS The meta-analysis incorporated 14 cohort studies. Nine papers were deemed to be of high quality based on the Newcastle-Ottawa Scale (NOS). Compared with normal weight (BMI 18.5-24.9 kg/m²), the overall pooled relative risks (RR) of GBC was 1.45 (95% CI 1.30-1.61) for excess body weight individuals (BMI ≥25 kg/m²); 1.10 (95% CI 1.02-1.18) for overweight persons (BMI 25-29.9 kg/m²) and 1.69(95% CI 1.54-1.86) for obese folks (BMI ≥30 kg/m²). A higher risk of GBC was presented in obese women (women: RR 1.78, 95% CI 1.59-1.99; men: RR 1.50, 95% CI 1.25-1.79). And a positive relationship between overweight and GBC risk was also displayed in female (RR 1.25, 95% CI 1.11-1.40), but not in male (RR 1.01, 95% CI 0.93-1.11). The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS This meta-analysis of 14 cohort studies demonstrated that raised BMI has a dramatic association with risk of GBC, especially in women. But, no association between overweight and GBC in men was found.


Odontogenic Tumours of Jaw: A Prospective Study on Clinico-Pathological Profile and Their Management.
Odontogenic tumours are a group of heterogeneous diseases that range from hamartomatous or non-neoplastic tissue proliferations to benign neoplasms to malignant tumours with metastatic potential. They are rare, comprising about <2-3% of all oral and maxillofacial biopsy specimens. The aim of the present study was to determine the clinico-pathological presentation of this heterogeneous group of lesions and review of literature. The present study was conducted in the ENT department of a Government Medical College and Hospital, West Bengal, India, over the period of 5 years from January 2011 to December 2015. It included a total of 15 patients who were clinico-radiologically diagnosed as odontogenic tumours, and were given appropriate treatment. Their diagnostic and management approaches are discussed. Among 15 odontogenic tumours, 13 were benign and two were malignant. Male to female ratio was 2:3. Mandible to maxilla ratio was 1.8:1. The patients were in between 4 and 56 years of age with highest incidence in 3rd decade of life. All patients are doing well till date with a minimum follow-up of 1 year. Incisional biopsy is considered as gold standard for preoperative diagnosis but FNAC can offer clinicians a less invasive alternative. CT is the choice of investigation for study of lesion, analysis of its extension and surgical planning. The challenge to proper management lies in balancing between conservative and radical approach to reduce morbidity and recurrence both. Final diagnosis is made by post-operative histopathological examination.


First Report of a Ceratobasidium sp. Causing Root Rot on Canola in Washington State.
Rhizoctonia root rot occurs commonly on canola (Brassica napus L.) in Washington State. Recently, isolates of an additional pathogen were found to be involved in this disease complex. Isolates of an AG-I-like Ceratobasidium sp. were collected from roots and root zone soil in central Washington near Ritzville. Identity of selected isolates was verified by sequencing the internal transcribed spacer (ITS) region of the rDNA (GenBank Accession Nos. JQ247570, JQ247571, and JQ247572), with a 90 to 93% identity to AG-I. All isolates also amplified with AG-I-like specific primers (1). Six isolates were included in pathogenicity assays conducted in the greenhouse. There were five replicates of three plants for each treatment and the experiment was conducted twice. Pasteurized soil was infested with ground oat inoculum (1%) and placed into containers (3.8 × 21 cm). Infested soils were seeded with canola, chickpea (Cicer arietinum L.), lentil (Lens culinaris Medik.), pea (Pisum sativum L.), barley (Hordeum vulgare L.), or wheat (Triticum aestivum L.). After 3 weeks of incubation at 15°C, the plants were destructively harvested. The emergence of canola was consistently reduced in soil infested with a Ceratobasidium sp., with reductions of 0 to 23% (average 11%). There was no postemergence damping-off, a symptom commonly associated with AG-2-1 (2). Plant height and top dry weights were significantly reduced for canola seeded into infested soil. Heights of plants growing in infested soil was reduced by 25 to 53% (average 42%) and top dry weight was reduced by 37 to 81% (average 61%) compared with the noninfested control. The legume hosts tested in this study were also affected by this Ceratobasidium sp., but to a lesser extent. Compared with the noninfested controls, there was evidence of preemergence damping-off in chickpea (0 to 27%, average 13%) and pea plants were consistently stunted (5 to 23%, average 12%). Chickpea and pea plants grown in infested soil also had reduced top dry weights of 9 to 28% (average 17%) and 13 to 35% (average 21%), respectively. The roots of all infected hosts had a characteristic brown discoloration with tapered, rotted root tips (spear tips). There was no reduction in emergence or plant height of wheat and barley; there was inconsistent reduction in dry weight of these plants. To our knowledge, this is the first report of a Ceratobasidium sp. causing disease on canola in Washington State. References: (1) P. A. Okubara et al. Phytopathology 98:837, 2008. (2) T. C. Paulitz et al. Plant Dis. 90:829, 2006.


Is Putting SUGAR (Sampling Utterances of Grammatical Analysis Revised) Into Language Sample Analysis a Good Thing? A Response to Pavelko and Owens (2017).
In this letter, the authors respond to Pavelko and Owens' (2017) newly advanced set of procedures for language sample analysis: Sampling Utterances and Grammatical Analysis Revised (SUGAR). The authors contrast some of the new guidelines for transcription, morpheme segmentation, and language sample elicitation in SUGAR with traditional conventions for language sample analysis (LSA). They address the potential impact of the new guidelines on some of the target measures in SUGAR-mean length of utterances in morphemes (MLUm), words per sentence (WPS), and clauses per sentence (CPS)-and provide their suggestions. Inclusion of partially intelligible utterances in SUGAR may over- or underestimate children's MLUm and reduce the reliability of computing WPS. Counting derivational morphemes and the component morphemes of catenatives (e.g., gonna) may result in overestimation of children's morphosyntactic skills. Further data are needed to determine whether MLUm including derivational morphemes and the component morphemes of catenatives is a better measure of children's morphosyntactic skills than MLUm excluding those morphemes. Pending such data, the authors recommend maintaining traditional LSA conventions and measures. Furthermore, free, fast automated utilities already exist that reduce barriers for clinicians to conduct informative, in-depth LSA.


Meteorological, environmental remote sensing and neural network analysis of the epidemiology of malaria transmission in Thailand.
In many malarious regions malaria transmission roughly coincides with rainy seasons, which provide for more abundant larval habitats. In addition to precipitation, other meteorological and environmental factors may also influence malaria transmission. These factors can be remotely sensed using earth observing environmental satellites and estimated with seasonal climate forecasts. The use of remote sensing usage as an early warning tool for malaria epidemics have been broadly studied in recent years, especially for Africa, where the majority of the world's malaria occurs. Although the Greater Mekong Subregion (GMS), which includes Thailand and the surrounding countries, is an epicenter of multidrug resistant falciparum malaria, the meteorological and environmental factors affecting malaria transmissions in the GMS have not been examined in detail. In this study, the parasitological data used consisted of the monthly malaria epidemiology data at the provincial level compiled by the Thai Ministry of Public Health. Precipitation, temperature, relative humidity, and vegetation index obtained from both climate time series and satellite measurements were used as independent variables to model malaria. We used neural network methods, an artificial-intelligence technique, to model the dependency of malaria transmission on these variables. The average training accuracy of the neural network analysis for three provinces (Kanchanaburi, Mae Hong Son, and Tak) which are among the provinces most endemic for malaria, is 72.8% and the average testing accuracy is 62.9% based on the 1994-1999 data. A more complex neural network architecture resulted in higher training accuracy but also lower testing accuracy. Taking into account of the uncertainty regarding reported malaria cases, we divided the malaria cases into bands (classes) to compute training accuracy. Using the same neural network architecture on the 19 most endemic provinces for years 1994 to 2000, the mean training accuracy weighted by provincial malaria cases was 73%. Prediction of malaria cases for 2001 using neural networks trained for 1994-2000 gave a weighted accuracy of 53%. Because there was a significant decrease (31%) in the number of malaria cases in the 19 provinces from 2000 to 2001, the networks overestimated malaria transmissions. The decrease in transmission was not due to climatic or environmental changes. Thailand is a country with long borders. Migrant populations from the neighboring countries enlarge the human malaria reservoir because these populations have more limited access to health care. This issue also confounds the complexity of modeling malaria based on meteorological and environmental variables alone. In spite of the relatively low resolution of the data and the impact of migrant populations, we have uncovered a reasonably clear dependency of malaria on meteorological and environmental remote sensing variables. When other contextual determinants do not vary significantly, using neural network analysis along with remote sensing variables to predict malaria endemicity should be feasible.


Age of onset has limited association with body mass index at time of presentation for anorexia nervosa: comparison of peak-onset and late-onset anorexia nervosa groups.
The clinical characteristics differentiating late-onset anorexia nervosa (AN) from typical pubertal onset AN remain unclear. The purpose of the present study was to examine these differences in a retrospective analysis. A total of 149 female AN patients was divided into two groups: a peak-onset AN group (n = 125) in which onset occurred between the ages of 15 and 24 years, and a late-onset AN group (n = 24) in which onset occurred at the age of > or =25 years. A logistic regression analysis was conducted with this classification as the target variable and five clinical factors as explanatory variables for the clinical characteristics at the time of initial examination. Body mass index (BMI) at the time of presentation was identified as a possible factor affecting classification as peak-onset or late-onset AN. In addition, a negative linear correlation was detected between age of onset and BMI at the time of initial examination. The results suggest that BMI at the time of the initial examination is an important clinical characteristic to differentiate peak-onset AN and late-onset AN.


Social relationship difficulties in autism and reactive attachment disorder: Improving diagnostic validity through structured assessment.
Autism Spectrum Disorder (ASD) versus Reactive Attachment Disorder (RAD) is a common diagnostic challenge for clinicians due to overlapping difficulties with social relationships. RAD is associated with neglect or maltreatment whereas ASD is not: accurate differential diagnosis is therefore critical. Very little research has investigated the relationship between the two, and it is unknown if standardised measures are able to discriminate between ASD and RAD. The current study aimed to address these issues. Fifty eight children with ASD, and no history of maltreatment, were group matched on age with 67 children with RAD. Group profiles on multi-informant measures of RAD were investigated and group differences explored. Discriminant function analysis determined assessment features that best discriminated between the two groups. Although, according to parent report, children with ASD presented with significantly fewer indiscriminate friendliness behaviours compared to the RAD group (p<0.001), 36 children with ASD appeared to meet core RAD criteria. However, structured observation clearly demonstrated that features were indicative of ASD and not RAD for all but 1 of these 36 children. Children with RAD and children with ASD may demonstrate similar social relationship difficulties but there appears to be a difference in the social quality of the interactions between the groups. In most cases it was possible to differentiate between children with ASD and children with RAD via structured observation. Nevertheless, for a small proportion of children with ASD, particularly those whose difficulties may be more subtle, our current standardised measures, including structured observation, may not be effective in differentiating RAD from ASD.


REPAIRtoire--a database of DNA repair pathways.
REPAIRtoire is the first comprehensive database resource for systems biology of DNA damage and repair. The database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases. REPAIRtoire contains information about eight main DNA damage checkpoint, repair and tolerance pathways: DNA damage signaling, direct reversal repair, base excision repair, nucleotide excision repair, mismatch repair, homologous recombination repair, nonhomologous end-joining and translesion synthesis. The pathway/protein dataset is currently limited to three model organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens. The DNA repair and tolerance pathways are represented as graphs and in tabular form with descriptions of each repair step and corresponding proteins, and individual entries are cross-referenced to supporting literature and primary databases. REPAIRtoire can be queried by the name of pathway, protein, enzymatic complex, damage and disease. In addition, a tool for drawing custom DNA-protein complexes is available online. REPAIRtoire is freely available and can be accessed at http://repairtoire.genesilico.pl/.


Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion.
An emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (SFTSV) is responsible for thousands of clinical cases and associated fatalities in China, Japan, and South Korea. Akin to other phleboviruses, SFTSV relies on a viral glycoprotein, Gc, to catalyze the merger of endosomal host and viral membranes during cell entry. Here, we describe the postfusion structure of SFTSV Gc, revealing that the molecular transformations the phleboviral Gc undergoes upon host cell entry are conserved with otherwise unrelated alpha- and flaviviruses. By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever virus, we show that these changes involve refolding of the protein into a trimeric state. Reverse genetics and rescue of site-directed histidine mutants enabled localization of histidines likely to be important for triggering this pH-dependent process. These data provide structural and functional evidence that the mechanism of phlebovirus-host cell fusion is conserved among genetically and patho-physiologically distinct viral pathogens.


Efficient multi-scale 3D CNN with fully connected CRF for accurate brain lesion segmentation.
We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network's soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available.


Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid.
Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be further metabolized to supposedly less active diols by the soluble epoxide hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we compared retinal vasculature development in wild-type and sEH(-/-) mice. Deletion of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation, a phenomenon associated with activation of the Notch signaling pathway. In the retina, sEH was localized in Müller glia cells, and Müller cell-specific sEH deletion reproduced the sEH(-/-) retinal phenotype. Lipid profiling revealed that sEH deletion decreased retinal and Müller cell levels of 19,20-dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 19,20-DHDP suppressed endothelial Notch signaling in vitro via inhibition of the γ-secretase and the redistribution of presenilin 1 from lipid rafts. Moreover, 19,20-DHDP, but not the parent epoxide, was able to rescue the defective angiogenesis in sEH(-/-) mice as well as in animals lacking the Fbxw7 ubiquitin ligase, which demonstrate strong basal activity of the Notch signaling cascade. These studies demonstrate that retinal angiogenesis is regulated by a novel form of neuroretina-vascular interaction involving the sEH-dependent generation of a diol of DHA in Müller cells.


The glycosaminoglycan-binding domain of decoy receptor 3 is essential for induction of monocyte adhesion.
Decoy receptor 3 (DcR3), a soluble receptor for Fas ligand, LIGHT (homologous to lymphotoxins shows inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes), and TNF-like molecule 1A, is highly expressed in cancer cells and in tissues affected by autoimmune disease. DcR3.Fc has been shown to stimulate cell adhesion and to modulate cell activation and differentiation by triggering multiple signaling cascades that are independent of its three known ligands. In this study we found that DcR3.Fc-induced cell adhesion was inhibited by heparin and heparan sulfate, and that DcR3.Fc was unable to bind Chinese hamster ovary K1 mutants defective in glycosaminoglycan (GAG) synthesis. Furthermore, the negatively charged, sulfated GAGs of cell surface proteoglycans, but not their core proteins, were identified as the binding sites for DcR3.Fc. A potential GAG-binding site was found in the C-terminal region of DcR3, and the mutation of three basic residues, i.e., K256, R258, and R259, to alanines abolished its ability to trigger cell adhesion. Moreover, a fusion protein comprising the GAG-binding region of DcR3 with an Fc fragment (DcR3_HBD.Fc) has the same effect as DcR3.Fc in activating protein kinase C and inducing cell adhesion. Compared with wild-type THP-1 cells, cell adhesion induced by DcR3.Fc was significantly reduced in both CD44v3 and syndecan-2 knockdown THP-1 cells. Therefore, we propose a model in which DcR3.Fc may bind to and cross-link proteoglycans to induce monocyte adhesion.


Anti-proliferative and apoptosis induction activity of green tea polyphenols on human promyelocytic leukemia HL-60 cells.
Anti-proliferation and apoptosis inducing effects of green tea polyphenols (GTPs) were studied against human promyeolcytic leukemia HL-60 cells. Anti-proliferation activity of GTPs against HL-60 cells and cytotoxicity against normal cells, V79-4 were measured with the MTT assay. Nuclear fragmentation of GTP-treated cells was observed with a fluorescence microscope and flow-cytometric analysis was performed to observe the appearance of apoptotic bodies. Changes in apoptosis-related protein levels were investigated by Western blot analysis. GTPs significantly reduced the HL-60 proliferation, however, they did not show significant inhibition in proliferation of normal V79-4 cells. GTP treatment induced apoptosis in HL-60 cells, evidenced by nuclei fragmentation and apoptotic body appearance. The expression level of Bcl-2 was decreased and caspase-3 was activated by GTP treatment. GTPs revealed anti-proliferative and apoptosis-inducing activity against HL-60 cells through the down-regulation of Bcl-2 and activation of caspase-3.


Possible consequences of the overlap between the CaMV 35S promoter regions in plant transformation vectors used and the viral gene VI in transgenic plants.
Multiple variants of the Cauliflower mosaic virus 35S promoter (P35S) are used to drive the expression of transgenes in genetically modified plants, for both research purposes and commercial applications. The genetic organization of the densely packed genome of this virus results in sequence overlap between P35S and viral gene VI, encoding the multifunctional P6 protein. The present paper investigates whether introduction of P35S variants by genetic transformation is likely to result in the expression of functional domains of the P6 protein and in potential impacts in transgenic plants. A bioinformatic analysis was performed to assess the safety for human and animal health of putative translation products of gene VI overlapping P35S. No relevant similarity was identified between the putative peptides and known allergens and toxins, using different databases. From a literature study it became clear that long variants of the P35S do contain an open reading frame, when expressed, might result in unintended phenotypic changes. A flowchart is proposed to evaluate possible unintended effects in plant transformants, based on the DNA sequence actually introduced and on the plant phenotype, taking into account the known effects of ectopically expressed P6 domains in model plants.


Optimizing Rubisco and its regulation for greater resource use efficiency.
Rubisco catalyses the carboxylation of ribulose-1,5-bisphosphate (RuBP), enabling net CO2 assimilation in photosynthesis. The properties and regulation of Rubisco are not optimal for biomass production in current and projected future environments. Rubisco is relatively inefficient, and large amounts of the enzyme are needed to support photosynthesis, requiring large investments in nitrogen. The competing oxygenation of RuBP by Rubisco decreases photosynthetic efficiency. Additionally, Rubisco is inhibited by some sugar phosphates and depends upon interaction with Rubisco activase (Rca) to be reactivated. Rca activity is modulated by the chloroplast redox status and ADP/ATP ratios, thereby mediating Rubisco activation and photosynthetic induction in response to irradiance. The extreme thermal sensitivity of Rca compromises net CO2 assimilation at moderately high temperatures. Given its central role in carbon assimilation, the improvement of Rubisco function and regulation is tightly linked with irradiance, nitrogen and water use efficiencies. Although past attempts have had limited success, novel technologies and an expanding knowledge base make the challenge of improving Rubisco activity in crops an achievable goal. Strategies to optimize Rubisco and its regulation are addressed in relation to their potential to improve crop resource use efficiency and climate resilience of photosynthesis.


Investigations of the modular structure of bacterial promoters.
Bacterial RNA polymerase holoenzyme carries different determinants that contact different promoter DNA sequence elements. These contacts are essential for the recognition of promoters prior to transcript initiation. Here, we have investigated how active promoters can be built from different combinations of elements. Our results show that the contribution of different contacts to promoter activity is critically dependent on the overall promoter context, and that certain combinations of contacts can hinder transcription initiation.


DeltaNp63 antagonizes p53 to regulate mesoderm induction in Xenopus laevis.
p63, a homolog of the tumor suppressor p53, is critical for the development and maintenance of complex epithelia. The developmentally regulated p63 isoform, DeltaNp63, can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological roles is unclear. Based on our initial finding that the mesoderm-inducing factor activin A is suppressed by DeltaNp63 in human keratinocytes, we investigated the role of DeltaNp63 in regulating mesoderm induction during early Xenopus laevis development. We find that down-regulation of DeltaNp63 by morpholino injection in the early Xenopus embryo potentiates mesoderm formation whereas ectopic expression of DeltaNp63 inhibits mesoderm formation. Furthermore, we show that mesodermal induction after down-regulation of DeltaNp63 is dependent on p53. We propose that a key function for p63 in defining a squamous epithelial phenotype is to actively suppress mesodermal cell fates during early development. Collectively, we show that there is a distinct requirement for different p53 family members during the development of both mesodermal and ectodermal tissues. These findings have implications for the role of p63 and p53 in both development and tumorigenesis of human epithelia.


Marine biodiversity in the Caribbean: regional estimates and distribution patterns.
This paper provides an analysis of the distribution patterns of marine biodiversity and summarizes the major activities of the Census of Marine Life program in the Caribbean region. The coastal Caribbean region is a large marine ecosystem (LME) characterized by coral reefs, mangroves, and seagrasses, but including other environments, such as sandy beaches and rocky shores. These tropical ecosystems incorporate a high diversity of associated flora and fauna, and the nations that border the Caribbean collectively encompass a major global marine biodiversity hot spot. We analyze the state of knowledge of marine biodiversity based on the geographic distribution of georeferenced species records and regional taxonomic lists. A total of 12,046 marine species are reported in this paper for the Caribbean region. These include representatives from 31 animal phyla, two plant phyla, one group of Chromista, and three groups of Protoctista. Sampling effort has been greatest in shallow, nearshore waters, where there is relatively good coverage of species records; offshore and deep environments have been less studied. Additionally, we found that the currently accepted classification of marine ecoregions of the Caribbean did not apply for the benthic distributions of five relatively well known taxonomic groups. Coastal species richness tends to concentrate along the Antillean arc (Cuba to the southernmost Antilles) and the northern coast of South America (Venezuela-Colombia), while no pattern can be observed in the deep sea with the available data. Several factors make it impossible to determine the extent to which these distribution patterns accurately reflect the true situation for marine biodiversity in general: (1) highly localized concentrations of collecting effort and a lack of collecting in many areas and ecosystems, (2) high variability among collecting methods, (3) limited taxonomic expertise for many groups, and (4) differing levels of activity in the study of different taxa.


Knowledge on uterine prolapse among married women of reproductive age in Nepal.
Uterine prolapse (UP), which affects about 10% of women of reproductive age in Nepal, is the most frequently reported cause of poor health in women of reproductive age and postmenopausal women. Currently, women's awareness of UP is unknown, and attempts to unravel the UP problem are inadequate. This study aims to assess UP knowledge among married reproductive women, and determine the association between UP knowledge and socioeconomic characteristics. Our cross-sectional descriptive study investigated 25 districts representing all five administrative regions, three ecological zones, and urban and rural settings. We used structured questionnaires to interview 4,693 married women aged 15-49 years. We assessed UP knowledge by asking women whether they had ever heard about UP, followed by specific questions about symptoms and preventive measures. Descriptive statistics characterized the study population regarding socioeconomic status, assessed how many participants had ever heard about UP, and determined UP knowledge level among participants who had heard about the condition. Simple regression analysis identified a possible association between socioeconomic characteristics, ever heard about UP, and level of UP knowledge. Mean age of participants was 30 years (SD [standard deviation] 7.4), 67.5% were educated, 48% belonged to the advantaged Brahmin and Chhetri groups, and 22.2% were Janajati from the hill and terai zones. Fifty-three percent had never heard about UP. Among women who had heard about UP, 37.5% had satisfactory knowledge. Any knowledge about UP was associated with both urban and rural settings, age group, and education level. However, satisfactory knowledge about UP was associated with administrative region, ecological zones, caste/ethnic group, and age group of women. Fifty-three percent of participants had never heard about UP, and UP knowledge level was satisfactory in 37.% of those who had ever heard about UP. Any knowledge was associated with urban/rural setting, age group, and education level, whereas satisfactory knowledge was associated with geography, caste/ethnic group, and age group. UP-related health promotion programs should target women from all caste/ethnic groups, age groups, and education levels, including urban and rural communities.


Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter.
Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose of 0.64 mg/kg body weight. The levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine, 1,N(6)-etheno-2'-deoxyadenosine, and 1-N(2)-etheno-2'-deoxyguanosine (εdG) were significantly increased with 23% (95% confidence interval [CI]: 0.1-45%), 54% (95% CI:18-90%), and 73% (95% CI: 31-134%) in the liver of rats exposed orally to CB, respectively. Rats orally exposed to PM from the wood stove area and low oxygen combustion WSPM (LOWS) had 35% (95% CI: 0.1-71%) and 45% (95% CI: 10-82%) increased levels of εdG in the liver, respectively. No significant differences were observed for bulky DNA adducts. Increased gene expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results indicate that WSPM and CB exert the strongest effect in terms of oxidative stress-induced response, inflammation, and genotoxicity in the organ closest to the port of entry.


Efficient optimization of diffractive optical elements based on rigorous diffraction models.
An efficient optimization strategy for the design of diffractive optical elements that is based on rigorous diffraction theory is described. The optimization algorithm combines diffraction models of different degrees of accuracy and computational complexity. A fast design algorithm for diffractive optical elements is used to yield estimates of the optimum surface profile based on paraxial diffraction theory. These estimates are subsequently evaluated with a rigorous diffraction model. This scheme allows one to minimize the need to compute diffraction effects rigorously, while providing accurate design. We discuss potential applications of this scheme as well as details of an implementation based on a modified Gerchberg-Saxton algorithm and the finite-difference time-domain method. Illustrative examples are provided in which we use the algorithm to design Fourier array illuminators.


An integrated console for capsule-based, automated organic synthesis.
The current laboratory practices of organic synthesis are labor intensive, impose safety and environmental hazards, and hamper the implementation of artificial intelligence guided drug discovery. Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions with prepacked capsules. The machine conducts coupling reactions and delivers the purified products with minimal user involvement. Two desirable reaction classes - the synthesis of saturated N-heterocycles and reductive amination - were implemented, along with multi-step sequences that provide drug-like organic molecules in a fully automated manner. We envision that this system will serve as a console for developers to provide synthetic methods as integrated, user-friendly packages for conducting organic synthesis in a safe and convenient fashion.


A conserved family of enzymes that phosphorylate inositol hexakisphosphate.
Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6.