Faster Rates of Molecular Sequence Evolution in Reproduction-Related Genes and in Species with Hypodermic Sperm Morphologies.
Sexual selection drives the evolution of many striking behaviors and morphologies and should leave signatures of selection at loci underlying these phenotypes. However, although loci thought to be under sexual selection often evolve rapidly, few studies have contrasted rates of molecular sequence evolution at such loci across lineages with different sexual selection contexts. Furthermore, work has focused on separate sexed animals, neglecting alternative sexual systems. We investigate rates of molecular sequence evolution in hermaphroditic flatworms of the genus Macrostomum. Specifically, we compare species that exhibit contrasting sperm morphologies, strongly associated with multiple convergent shifts in the mating strategy, reflecting different sexual selection contexts. Species donating and receiving sperm in every mating have sperm with bristles, likely to prevent sperm removal. Meanwhile, species that hypodermically inject sperm lack bristles, potentially as an adaptation to the environment experienced by hypodermic sperm. Combining functional annotations from the model, Macrostomum lignano, with transcriptomes from 93 congeners, we find genus-wide faster sequence evolution in reproduction-related versus ubiquitously expressed genes, consistent with stronger sexual selection on the former. Additionally, species with hypodermic sperm morphologies had elevated molecular sequence evolution, regardless of a gene's functional annotation. These genome-wide patterns suggest reduced selection efficiency following shifts to hypodermic mating, possibly due to higher selfing rates in these species. Moreover, we find little evidence for convergent amino acid changes across species. Our work not only shows that reproduction-related genes evolve rapidly also in hermaphroditic animals, but also that well-replicated contrasts of different sexual selection contexts can reveal underappreciated genome-wide effects.


Intraperitoneal chemotherapy in the management of ovarian cancer.
Initial phase I trials of intraperitoneal chemotherapy in ovarian cancer patients demonstrated that a pharmacologic advantage was achieved with the direct instillation of drugs into the peritoneal cavity. Recent trials have reported that approximately 30% of patients who have small-volume residual disease following induction chemotherapy will achieve a complete remission with intraperitoneal cisplatin. The demonstrated effectiveness and acceptable toxicity makes cisplatin the current drug of choice in the intraperitoneal therapy of ovarian cancer patients. Additional clinical studies are required to determine the role of combinations intraperitoneally, the necessity of intravenous sodium thiosulfate for use with intraperitoneal cisplatin, the activity of other agents, the optimum techniques to deliver intraperitoneal drugs, and the appropriate clinical situations where intraperitoneal therapy should be used in the overall management of ovarian cancer.


Synaptic unreliability facilitates information transmission in balanced cortical populations.
Synaptic unreliability is one of the major sources of biophysical noise in the brain. In the context of neural information processing, it is a central question how neural systems can afford this unreliability. Here we examine how synaptic noise affects signal transmission in cortical circuits, where excitation and inhibition are thought to be tightly balanced. Surprisingly, we find that in this balanced state synaptic response variability actually facilitates information transmission, rather than impairing it. In particular, the transmission of fast-varying signals benefits from synaptic noise, as it instantaneously increases the amount of information shared between presynaptic signal and postsynaptic current. Furthermore we show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not reach an optimum at a finite noise level.


New insights into changing honey bee (Apis mellifera) immunity molecules pattern and fatty acid esters, in responses to Ascosphaera apis infection.
Monitoring of metabolite changes could provide valuable insights into disturbances caused by an infection and furthermore, could be used to define the status of an organism as healthy or diseased and define what could be defensive elements against the infection. The present investigation conducted a gas chromatography-mass spectrometry (GC/MS) for haemolymph of larval honey bees (Apis mellifera L.) infected with the fungal pathogen Ascosphaera apis in comparison with control haemolymph non-infected insects. Results revealed that the pathogen caused a general disturbance of metabolites detected in the haemolymph of the honey bee. The majority of metabolites identified before and after infection were fatty acid esters. The disease caused an elevation in levels of methyl oleate, methyl palmitate, and methyl stearate, respectively. Further, the disease drove to the disappearance of methyl palmitoleate, and methyl laurate. Conversely, methyl linolelaidate, and ethyl oleate were identified only in infected larvae. A high reduction in diisooctyl phthalate was recorded after the infection. Interestingly, antimicrobial activities were confirmed for haemolymph of infected honey bee larvae. In spite of the presence of some previously known bioactive compounds in healthy larvae there were no antimicrobial activities.


Use of Pathology Data to Improve High-Value Treatment of Cervical Neoplasia.
We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.


Early implanon discontinuation and associated factors among women ever used implanon in Mettu district, Oromia regional state, southwest Ethiopia, 2021.
Implanon is an effective form of long-acting reversible contraceptive used to prevent conception with a clinical failure rate of less than one per 100 users. However, in sub-Saharan countries the utilization of implanon was very low. Regardless of low utilization; its early discontinuation is very common in most developing countries including Ethiopia. To assess the prevalence of early implanon discontinuation and associated factors among women ever used implanon in Mettu district. A community based cross-sectional study design was conducted from October 11 to December 4, 2020 G C. A total of 430 women were included in the study by systematic random sampling technique. Data were entered into epi data version 3.1 and analyzed by SPSS version 25.0. Descriptive analysis was computed to describe descriptive results. Logistics regression was computed to see the relative effect of factors on the outcome variable. Adjusted odds ratio was calculated with 95% confidence intervals to show strength of association and p-value < 0.05 was used to declare statistical significance. The finding of the study was presented using narrations, tables and chart. The total proportion of early implanon discontinuation among 430 mothers was 19.3%. Women who did not counseled about the presence of alternatives methods [AOR = 2.28: 95% CI (1.22-4.26)], women who experienced dizziness after insertion of implanon [AOR = 1.90: 95% CI (1.06-3.43)] and being having menstrual disturbance after insertion of implanon [AOR = 2.17: 95% CI (1.16-4.08)] were significantly associated with early implanon discontinuation. Women who were counseled about the advantage of implanon [AOR: 0.49: 95% CI (0.28-0.87)] were protective from early implanon discontinuation. Early implanon discontinuation among mothers was found to be high. Hence, effective counseling on advantages and side effects of implanon and proper management of the side effects should be made to increase implanon retention.


Developing a training program to improve supervisor-resident relationships, step 1: defining the types of issues.
By some estimates, the teacher-learner relationship explains roughly half of the variance attributed to the effectiveness of teaching. Despite this, relationships largely have been ignored in the educational literature. This qualitative pilot study sought to identify factors in the supervisor-resident relationship that hinder learning among University of Toronto psychiatry residents. Thirteen postgraduate-year residents in Years 2-5 and their supervisors were interviewed regarding interactions that either assisted or adversely affected learning. Qualitative analysis of the interview data led to the identification of 5 types of issues affecting the supervisory relationship: goals and individual differences, communication and feedback, power and rivalry, support and collegiality, and role modeling and expertise. Face validity was supported when typed anonymous written feedback obtained from annual supervisor evaluations also could be organized into the 5 categories. Recognition of the types of interpersonal interactions that assist or hinder learning may contribute to enhanced teaching effectiveness.


Small molecule-based tandem solar cells with solution-processed and vacuum-processed photoactive layers.
A tandem solar cell device whose sub-cells are fabricated exclusively from small molecules (SMs) through both solution-processed and vacuum-processed deposition techniques is described. The front sub-cell's active layer consists of a bulk heterojunction (BHJ) DPP(TBFu)2:PC70BM device while the back cell has a typical bilayer structure employing a 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl] squaraine (SQ) donor and a C60 acceptor.


Primary cilia found on HeLa and other cancer cells.
For many years now, researchers have known of a sensory appendage on the surface of most differentiated cell types called primary cilium. Primary cilia are both chemo- and mechano-sensory in function and have an obvious role in cell cycle control. Because of this, it has been thought that primary cilia are not found on rapidly proliferating cells, for example, cancer cells. Here we report using immunofluorescent staining for the ciliary protein Arl13b that primary cilia are frequently found on HeLa (human epithelial adenocarcinoma) and other cancer cell lines such as MG63 (human osteosarcoma) commonly used for cell culture studies and that the ciliated population is significantly higher (ave. 28.6% and 46.5%, respectively in starved and 15.7-18.6% in un-starved cells) than previously anticipated. Our finding impacts the current perception of primary cilia formed in highly proliferative cells.


Notes on necropsy.
From the above it can be seen that autopsy is not a grotesque, macabre procedure performed for peculiar and disreputable reasons in a remote corner of the hospital. On the contrary, it is a scientific study designed to forward our knowledge of health and disease by the three primary methods of service, teaching and research. The examination of a dead body is always an emotional procedure. The pathologist and those concerned with frequent performance of autopsies become accustomed to it. To witness an autopsy may cause considerable emotional reaction in inexperienced people. As part of the learning experience, it can be very useful and appropriate staff are welcome to attend by arrangement. As proper protection garments are required and the suitability of viewing certain autopsies may arise, a formal request to the responsible pathologist is necessary. Whatever one's religious beliefs, it may be helpful to think of the deceased person's body as something which he or she has used during life, but which is no longer in any real way the persons once life has departed. The decreased body must be treated with dignity and respect as representing the remains of what was a human being and because of the natural desire of the next of kin that the remains of their relative should so be treated; it is not the person who used the body during life.


The metabolic syndrome--a neuroendocrine disorder?
Central obesity is a powerful predictor for disease. By utilizing salivary cortisol measurements throughout the day, it has now been possible to show on a population basis that perceived stress-related cortisol secretion frequently is elevated in this condition. This is followed by insulin resistance, central accumulation of body fat, dyslipidaemia and hypertension (the metabolic syndrome). Socio-economic and psychosocial handicaps are probably central inducers of hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. Alcohol, smoking and traits of psychiatric disease are also involved. In a minor part of the population a dysregulated, depressed function of the HPA axis is present, associated with low secretion of sex steroid and growth hormones, and increased activity of the sympathetic nervous system. This condition is followed by consistent abnormalities indicating the metabolic syndrome. Such 'burned-out' function of the HPA axis has previously been seen in subjects exposed to environmental stress of long duration. The feedback control of the HPA axis by central glucocorticoid receptors (GR) seems inefficient, associated with a polymorphism in the 5' end of the GR gene locus. Homozygotes constitute about 14% of Swedish men (women to be examined). Such men have a poorly controlled cortisol secretion, abdominal obesity, insulin resistance and hypertension. Furthermore, polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity, with elevated and low blood pressure, respectively. These results suggest a complex neuroendocrine background to the metabolic syndrome, where the kinetics of the regulation of the HPA axis play a central role.


Gestational weight gain and group prenatal care: a systematic review and meta-analysis.
Group visits for chronic medical conditions in non-pregnant populations have demonstrated successful outcomes including greater weight loss compared to individual visits for weight management. It is plausible that group prenatal care can similarly assist women in meeting gestational weight gain goals. The purpose of this study was to evaluate the effect of group vs. traditional prenatal care on gestational weight gain. A keyword search of Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and Google Scholar was performed up to April 2017. Studies were included if they compared gestational weight gain in a group prenatal care setting to traditional prenatal care in either randomized controlled trials, cohort, or case-control studies. The primary and secondary outcomes were excessive and adequate gestational weight gain according to the Institute of Medicine guidelines. Heterogeneity was assessed with the Q test and I2 statistic. Pooled relative risks (RRs) and confidence intervals (CI) were reported with random-effects models from the randomized controlled trials (RCT) and cohort studies. One RCT, one secondary analysis of an RCT, one study with "random assignment", and twelve cohort studies met the inclusion criteria for a total of 13,779 subjects. Thirteen studies used the CenteringPregnancy model, defined by 10 sessions that emphasize goal setting and self-monitoring. Studies targeted specific populations such as adolescents, African-Americans, Hispanics, active-duty military or their spouses, and women with obesity or gestational diabetes. There were no significant differences in excessive [7 studies: pooled rates 47% (1806/3582) vs. 43% (3839/8521), RR 1.09, 95% CI 0.97-1.23] or adequate gestational weight gain [6 studies: pooled rates 31% (798/2875) vs. 30% (1410/5187), RR 0.92, 95% CI 0.79-1.08] in group and traditional prenatal care among the nine studies that reported categorical gestational weight gain outcomes in the meta-analysis. Group prenatal care was not associated with excessive or adequate gestational weight gain in the meta-analysis. Since outcomes were overall inconsistent, we propose that prenatal care models (e.g., group vs. traditional) should be evaluated in a more rigorous fashion with respect to gestational weight gain.


A meta-analysis of spinal surgical site infection and vancomycin powder.
Surgical site infection (SSI) is a serious and costly complication of spinal surgery. There have been several conflicting reports on the use of intrawound vancomycin powder in decreasing SSI in spine surgery. The purpose of this study is to answer the question: "Does intrawound vancomycin powder reduce the rate of SSIs in spine surgery?" A comprehensive search of multiple electronic databases and bibliographies was conducted to identify clinical studies that evaluated the rates of SSI with and without the use of intrawound vancomycin powder in spine surgery. Independent reviewers extracted data and graded the quality of each paper that met inclusion criteria. A random effects meta-analysis was then performed. The search identified 9 retrospective cohort studies (Level III evidence) and 1 randomized controlled trial (Level II evidence). There were 2574 cases and 106 infections in the control group (4.1%) and 2518 cases and 33 infections (1.3%) in the treatment group, yielding a pooled absolute risk reduction and relative risk reduction of 2.8% and 68%, respectively. The meta-analysis revealed the use of vancomycin powder to be protective in preventing SSI (relative risk = 0.34, 95% confidence interval 0.17-0.66, p = 0.021). The number needed to treat to prevent 1 SSI was 36. A subgroup analysis found that patients who had implants had a reduced risk of SSI with vancomycin powder (p = 0.023), compared with those who had noninstrumented spinal operations (p = 0.226). This meta-analysis suggests that the use of vancomycin powder may be protective against SSI in open spinal surgery; however, the exact population in which it should be used is not clear. This benefit may be most appreciated in higher-risk populations or in facilities with a high baseline rate of infection.


The Rare Variant rs35356162 in UHRF1BP1 Increases Bladder Cancer Risk in Han Chinese Population.
Background: Seventeen loci have been found to be associated with bladder cancer risk by genome-wide association studies (GWAS) in European population. However, little is known about contribution of low-frequency and rare variants to bladder cancer susceptibility, especially in Eastern population. Methods: We performed a three-stage case-control study including 3,399 bladder cancer patients and 4,647 controls to identify low-frequency and rare variants associated with bladder cancer risk in Han Chinese. We examined exome-array data in 1,019 bladder cancer patients and 1,008 controls in discovery stage. Two replication stages were included to validate variants identified. Bonferroni adjustment was performed to define statistical significance. Logistic regression was conducted to evaluate single marker association with bladder cancer risk. We used SKAT-O method to perform gene level-based analysis. We also conduct additional experiments to explore the underlying mechanism of filtered gene(s). Results: We identified a novel rare coding variant (rs35356162 in UHRF1BP1: G > T, OR = 4.332, P = 3.62E-07 < 7.93E-07, Bonferroni cutoff) that increased bladder cancer risk in Han Chinese. Gene-level analysis showed a significant association of UHRF1BP1 (P = 4.47E-03) with bladder cancer risk. Experiments indicated down-regulation of UHRF1BP1 promoted migration and invasion through epithelial-mesenchymal transition in bladder cancer cell lines. Conclusion: The rare variant of UHRF1BP1, rs35356162, increases bladder cancer risk in Han Chinese and UHRF1BP1 might act as a tumor suppressor in bladder cancer development and progression. Summary: Little is known about potential contribution of low-frequency and rare variants to bladder cancer susceptibility. We performed a three-stage case-control study and identified a new rare variant, rs35356162 in UHRF1BP1, which increased bladder cancer risk in Han Chinese.


Translating DREAMS into practice: Early lessons from implementation in six settings.
The 'DREAMS Partnership' promotes a multi-sectoral approach to reduce adolescent girls and young women's (AGYW) vulnerability through a core package of interventions targeting multiple sources of HIV risk-to promote Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) lives. Implementation of such multi-sectoral programmes is complex and requires adaptation to national and local contexts. We describe the early implementation of DREAMS in diverse settings, to identify lessons for the scale-up and replication of combination programmes for young people. As part of evaluations underway in six DREAMS sites in three countries (Kenya, South Africa and Zimbabwe), we draw on process evaluation data collected from focus group discussions, key informant interviews, and in-depth interviews with beneficiaries, parents/caregivers, programme managers and opinion leaders. Additionally, structured observations were conducted and Gantt charts completed upon consultation with implementers. We concurrently reviewed documentation available on DREAMS and held cross-site discussions to interpret findings. All sites sought to implement all components of the DREAMS core package, but how and when they were implemented varied by context. Models of delivery differed, with either multiple or single partners responsible for some or all interventions. Key challenges included the urgent and ambitious expectations of DREAMS; 'layering' multiple interventions across different sectors (health, education, social welfare); supporting individuals' journeys between services to improve uptake and retention; engaging communities beyond direct beneficiaries; avoiding perceived/actual exclusivity; and ensuring continuity of commitment and funding for DREAMS. Despite significant challenges, DREAMS was well-received in the communities and perceived by both beneficiaries and implementers to empower AGYW to remain HIV negative. Structures, protocols and tools were introduced to strengthen referrals and deliver services targeted to the age and circumstances of young people. The benefits of combinations or integrated 'packages' of interventions are increasingly recognised. Early implementation of DREAMS provides useful lessons for improving coordination across multiple partners using a phased, systematic approach, regular adaptions to each unique context, and ensuring community ownership.


Fatalities above 30,000 feet: characterizing pediatric deaths on commercial airline flights worldwide.
We conducted this study to characterize in-flight pediatric fatalities onboard commercial airline flights worldwide and identify patterns that would have been unnoticed through single case analysis of these relative rare events. Retrospective cohort study of pediatric in-flight medical emergencies resulting in fatalities between January 2010 and June 2013. A ground-based medical support center providing remote medical support to commercial airlines worldwide. Children (age 0-18 yr) who experienced a medical emergency resulting in death during a commercial airline flight. None. There were a total of 7,573 in-flight medical emergencies involving children reported to the ground-based medical support center, resulting in 10 deaths (0.13% of all pediatric in-flight emergencies). The median subject age was 3.5 months with 90% being younger than 2 years, the age until which children are allowed to travel sharing a seat with an adult passenger, also known as lap infants. Six patients had no previous medical history, with one suffering cardiorespiratory arrest after developing acute respiratory distress during flight and five found asystolic (including four lap infants). Four subjects had preflight medical conditions, including two children traveling for the purpose of accessing advanced medical care. Pediatric in-flight fatalities are rare, but death occurs most commonly in infants and in subjects with a preexisting medical condition. The number of fatalities involving seemingly previously healthy children under the age of 2 years (lap infants) is intriguing and could indicate a vulnerable population at increased risk of death related to in-flight environmental factors, sleeping arrangements, or yet another unrecognized factor.


The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine.
Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.


Influence of nanosecond pulsed plasma on the non-enzymatic pathway for the generation of nitric oxide from L-arginine and the modification of graphite oxide to increase the solar cell efficiency.
In this work, we demonstrated the action of nanosecond pulsed plasma (NPP) on the generation of nitric oxide (NO) from the non-enzymatic pathway and on the modification of graphite oxide (GO) sheets to increase polymer solar cells (PSCs) efficiency. NO is an important signal and an effector molecule in animals, which is generated from the enzyme-catalyzed oxidation of L-arginine to NO and L-citrulline. Hence, L-arginine is an important biological precursor for NO formation. Therefore, we developed a new non-enzymatic pathway for the formation of NO and L-citrulline using NPP and characterized the pathway using NO detection kit, NMR, liquid chromatography/capillary electrophoresis-mass spectrometry (LC/CE-MS) for both quantitative and qualitative bioanalysis. We then synthesized and modified the functional groups of GO using NPP, and it was characterised by X-ray photoelectron spectroscopy (XPS), confocal Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) imaging, cathodoluminescence (CL) and work function using γ-FIB. Further, we also tested the power conversion efficiency of the PSCs devices with modified GO that is similar to the one obtained with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) as HTL. This work is perceived to have great implications for inexpensive and efficient methodology for NO generation and modification of GO, which are applicable in materials from nanomaterials to biomolecules.


Detection of Coxiella burnetii in cow's milk by PCR-enzyme-linked immunosorbent assay combined with a novel sample preparation method.
The use of an adequate concentration of Triton X-100 enhanced immunomagnetic separation of Coxiella burnetii from milk. PCR-enzyme-linked immunosorbent assay (PCR-ELISA) could detect coxiellas more sensitively than could conventional PCR. PCR-ELISA is therefore thought to be suitable for the simultaneous assay of a large number of samples. However, the number of cows from which raw milk tested positive for coxiellas by PCR-ELISA was inconsistent with that found with the antibody to coxiella by indirect immunofluorescence assay. The inconsistency is thought to be associated with the differences in the infectious route, infectious dose, or the timing of yielding the antibody and the period of duration of the antibody.


Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells by targeting NF‑κB pathway.
Uveal melanoma (UM) is a highly aggressive intraocular malignancy that lacks any effective targeted-therapy. Neither survival nor prognosis has been improved for the past decades in patients with metastatic UM. NF‑κB pathway is reported to be abnormally activated in UM. However, the role of NF‑κB pathway as a potential therapeutical target in UM remains unclear. Here, the effect of pristimerin, a potent inhibitor of NF‑κB pathway, on UM cells in terms of growth, apoptosis, motility, invasion and cancer stem-like cells (CSCs) was evaluated in vitro. We showed that pristimerin suppressed tumor necrosis factor α (TNFα)-induced IκBα phosphorylation, translocation of p65, and expression of NF‑κB-dependent genes. Moreover, pristimerin decreased cell viability and clonogenic ability of UM cells. A synergistic effect was observed in the treatment of pristimerin combined with vinblastine, a frontline therapeutic agent, in UM. Pristimerin led to a significant increase in the Annexin V+ cell population as measured by flow cytometry. We also observed that pristimerin impaired the abilities of migration and invasion in UM cells. Furthermore, pristimerin eliminated the ALDH+ cells and weakened serial re-plating ability of melanosphere. Collectively, pristimerin shows remarkable anticancer activities in UM cells through inactivating NF‑κB pathway, revealing that pristimerin may be a promising therapeutic agent in UM.


Substance use patterns and unprotected sex among street-involved youth in a Canadian setting: a prospective cohort study.
Rates of sexually transmitted infections (STI) and unplanned pregnancy are high among youth. While the intersection between drug and alcohol use and unprotected sex is well recognized, few studies have examined the relationship between substance use patterns and unprotected sex among high risk-populations such as street-involved youth. Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort of street-involved youth from Vancouver, Canada. Generalized estimating equations (GEE) were used to examine substance use patterns that were independently associated with unprotected sex, defined as (vaginal or anal) sexual intercourse without consistent condom use. Between September 2005 and May 2013, 1,026 youth were recruited into the ARYS cohort and 75% (n = 766) reported engaging in recent unprotected sex at some point during the study period. In a multivariable analysis, female gender (adjusted odds ratio [AOR] = 1.46, 95% confidence interval [CI]: 1.18-1.81), Caucasian ancestry (AOR = 1.38, 95% CI: 1.13-1.68), being in a stable relationship (AOR = 4.64, 95% CI: 3.82-5.65), having multiple sex partners (AOR = 2.60, 95% CI: 2.18-3.10) and the following substance use patterns were all independently associated with recent unprotected sex: injection or non-injection crystal methamphetamine use (AOR = 1.21, 95% CI: 1.03-1.43), injection or non-injection cocaine use (AOR = 1.20, 95% CI: 1.02-1.41), marijuana use (AOR = 1.23, 95% CI: 1.02-1.49), ecstasy use (AOR = 1.23, 95% CI: 1.01-1.48) and alcohol use (AOR = 1.31, 95% CI: 1.11-1.55) (all p < 0.05). Unprotected sex was prevalent among street-involved youth in this setting, and independently associated with female gender and a wide range of substance use patterns. Evidence-based and gender-informed sexual health interventions are needed in addition to increased access to youth-centered addiction treatment services. STI testing and linkages to healthcare professionals remain important priorities for street-involved youth, and should be integrated across all health and social services.


[Two cases of sellar chordomas. Ultrastructural and histochemical study (author's transl)].
Two cases of sellar chordomas are reported, with ultrastructural and histochemical study. The embryological origin and the histochemical data are discussed. The question of chondroid chordomas is evoked and the results of the ultrastructural study are interpreted on the basis of the cases hitherto reported. Special attention is called to the methods for the detection of polysaccharides by electron microscopy in such proliferations. Tissue culture seems to be able of providing a good information as to the secretory activity of the chordomas located at the skull base.


Towards automated biomedical ontology harmonization.
The use of biomedical ontologies is increasing, especially in the context of health systems interoperability. Ontologies are key pieces to understand the semantics of information exchanged. However, given the diversity of biomedical ontologies, it is essential to develop tools that support harmonization processes amongst them. Several algorithms and tools are proposed by computer scientist for partially supporting ontology harmonization. However, these tools face several problems, especially in the biomedical domain where ontologies are large and complex. In the harmonization process, matching is a basic task. This paper explains the different ontology harmonization processes, analyzes existing matching tools, and proposes a prototype of an ontology harmonization service. The results demonstrate that there are many open issues in the field of biomedical ontology harmonization, such as: overcoming structural discrepancies between ontologies; the lack of semantic algorithms to automate the process; the low matching efficiency of existing algorithms; and the use of domain and top level ontologies in the matching process.


Underutilization of calcium and vitamin D by older adults in a large general internal medicine practice.
The underutilization of calcium and vitamin D supplements in the prevention and treatment of osteoporosis is common among high-risk elders. Less is known about the prevalence and adequacy of calcium and vitamin D use by the general population of older adults. We performed a retrospective chart analysis of 617 women and 383 men over the age of 60 (mean age 73 +/- 9 years) seen at an internal medicine practice to establish the prevalence and evaluate the adequacy of calcium and vitamin D supplementation. Adequate supplementation was defined according to the National Osteoporosis Foundation guidelines and the National Institutes of Health Consensus Development Panel on Osteoporosis. Osteoporosis or osteopenia was documented in 207 (33.6%) women and 21 (5.5%) men (P < 0.01). Of 383 men, 116 (30.3%) used calcium, 25 (6.5%) used adequate doses of calcium, 109 (28.5%) used vitamin D, and only 8 (2.1%) used adequate doses of vitamin D. Of 617 women, 415 (67.3%) used calcium, 199 (32.3%) used adequate doses of calcium, 347 (56.2%) used vitamin D, and 83 (21.7%) used adequate doses of vitamin D. When compared with women, men were less likely to be on calcium (OR 0.21, 95% CI 0.16-0.28), on adequate calcium replacement (OR0.15, 95% CI 0.11-0.23), on vitamin D (OR 0.32, 95% CI 0.25-0.42), and on adequate vitamin D replacement (OR 0.13, 95% CI 0.07-0.26). Calcium and vitamin D were greatly underutilized among older patients in an internal medicine clinic. Inadequate replacement doses were common, and men were particularly susceptible to undertreatment.


Effect of exercise training on sports enjoyment and leisure-time spending in adolescents with complex congenital heart disease: the moderating effect of health behavior and disease knowledge.
The aim of this study was to evaluate the effects of a standardized exercise program on sports enjoyment and leisure-time spending in adolescents with congenital heart disease and to know what the moderating impact of their baseline health behavior and disease knowledge is. Included were 93 patients, aged 10 to 25, with surgical repair for tetralogy of Fallot or with a Fontan circulation for single-ventricle physiology, of 5 participating centers of pediatric cardiology in The Netherlands. They were randomly allocated, stratified for age, gender, and type of congenital heart disease to a 12-week period with either: (1) three times per week standardized exercise training or (2) care as usual (randomization ratio 2:1). At baseline and after 12 weeks, participants completed Web-based questionnaires and were interviewed by phone. Primary analyses tested changes from baseline to follow-up in sports enjoyment and leisure-time spending in the exercise group vs. control group. Secondary analyses concerned the moderating influence of baseline health behavior and disease knowledge on changes from baseline to follow-up, and comparison with normative data. At follow-up, the exercise group reported a decrease in passive leisure-time spending (watching television and computer usage) compared with controls. Exercise training had no effect on sports enjoyment and active leisure-time spending. Disease knowledge had a moderating effect on improvement in sports enjoyment, whereas health behavior did not. Compared with normative data, patients obtained similar leisure time scores and lower frequencies as to drinking alcohol and smoking. Exercise training decreased passive, but not active, leisure-time spending. It did not influence sports enjoyment.


Modeling absorbance-modulation optical lithography in photochromic films.
A kinetic model describing the conversion of a photochromic layer under complex illumination conditions is applied to absorbance-modulation optical lithography to determine the influence of the material characteristics on the confinement to subdiffraction dimensions of the transmitted dose. We show that the most important parameters are the intensity ratio between the confining and writing beams, the overall absorption at the writing wavelength, the relative absorption coefficients, and the photoreaction quantum yields at the two wavelengths. As the confining beam ultimately determines the transferred dose pattern, we conclude that the modulation of the writing beam is not strictly necessary to produce subwavelength apertures.


[New recombinant variant of human immunodeficiency virus of type 1, subtype envB/envA, isolated in Novosibirsk].
The nucleotide sequence of the variant of human immunodeficiency virus of type 1 (HIV-1), mostly widespread on the territory of the Novosibirsk region, was determined. The analysis of the nucleotide sequence confirmed that this variant belonged to HIV-1 of subtype A. The HIV-1 recombinant variant of subtype envB/envA with the recombination area within the second conservative region C2 of gene env, so far unknown, was detected and characterized. In HIV-1 the area at the beginning of gene env (5'-env) was found to belong to subtype B and the sequence at the end of gene env (3'-env), to subtype A. The analysis of the amino acid sequence of the third variable region of gene env demonstrated that the viruses under study belonged to macrophagotropic "slow/low" variants, characterized by low replication speed. The analysis of nucleotide sequences of the isolated variants of HIV-1 revealed their close genetic relationship with HIV-1 isolates circulating on the territory of Ukraine.


Costs and quality of life of multiple sclerosis in Austria.
This cost-of-illness analysis is part of a Europe-wide study on the costs of multiple sclerosis (MS) and is based on information from patients in Austria. The objective was to estimate the costs and quality of life (QOL) related to the level of disease severity and progression. Questionnaires were sent to 2995 patients registered with a nationwide patient organization. Patients were asked to provide details regarding the type of disease, relapses, level of functional disability, resource consumption (medical and non-medical), work absence, sick leave and informal care, as well as QOL. Surveys from a total of 1.019 (34.0%) patients were used in the analysis, of which the mean (standard deviation [SD]) age was 50 (12.2) years; 70% of patients were female. Patients with mild disease (Expanded Disability Status Scale [EDSS] score 0-3) represented 41% of patients, 36% had moderate disease (EDSS score 4-6.5) and 22% had severe disease (EDSS score > or =7). The mean (SD) EDSS score in the sample was 4.4 (2.4), with a mean (SD) utility of 0.55 (0.32). Costs are presented from the societal perspective as well as from the viewpoint of payers of care and invalidity. Mean total annual costs for an average patient in the sample were estimated at euro 40.300 in the societal perspective, whereas payers' costs were estimated at only half of this. Disease-modifying drugs represented a quarter of all costs in the payer perspective, but only 12% of societal costs. For society, the highest cost was the loss of productivity (36%), while payments for this loss (invalidity pensions and sick-leave compensation) accounted for only 21% of total costs to payers. Costs are highly correlated with disease progression, increasing four-fold from early disease to very severe disease (euro 16.000 to euro 63.800). Mean annual costs per patient reported are thus determined by the distribution of disease severity in the sample. Workforce participation decreases from roughly 75% in early disease to less than 10% in the late stages, despite the fact that 70% of patients with an EDSS score of 8 or 9 are still below the official retirement age. Consequently, productivity losses increase over fivefold. In parallel, costs of informal care increase from euro 325 per year at an EDSS score of 0-1 to over euro 20.000 at an EDSS score of 8-9. Hospitalization is very infrequent in early disease, representing less than euro 1.000 for patients with an EDSS score of 0-1, but increases steeply for patients with an EDSS score > or =5. QOL, measured as utility scores, decreases rapidly from almost 0.90 to 0.05 as disability becomes severe. However, the loss of utility is evident at all disease levels. Young patients with an EDSS score of approximately 2 have a utility that is 0.15 lower than matched individuals from the general population. This loss increases to approximately 0.4 for patients over 60 years of age with an average EDSS score of 6.0-6.5. Patients with a recent relapse had lower utility (-0.1) and higher costs (+ euro 4.750).


Growth in children with congenital heart disease.
We sought to describe growth in young children with congenital heart disease (CHD) over time. We performed a retrospective matched cohort study, identifying children with CHD in a large primary care network in Pennsylvania, New Jersey, and Delaware and matching them 10:1 with control subjects. The primary endpoint was the difference in mean World Health Organization z score for cases and controls for weight-for-age (WFAZ), length-for-age (LFAZ), weight-for-length (WFLZ), and head circumference-for-age (HCFAZ) at traditional ages for preventive visits, stratified by CHD category. We evaluated 856 cases: 37 with single ventricle (SV) physiology, 52 requiring complex repair (CR), 159 requiring simple repair (SR), and 608 requiring no repair. For children in the SV, CR, and SR categories, large, simultaneous, and statistically significant (Student's t test P < .05) decreases in WFAZ and LFAZ appeared within the first month of life, peaked near 4 months, and persisted through 24 or 36 months. There were fewer and smaller decreases in the no-repair group between 2 and 18 months. HC data were available between 1 week and 24 months; at those ages, decreases in mean HCFAZ generally paralleled decreases in WFAZ and LFAZ in the SV, CR, and SR groups. Children with CHD experience early, simultaneous decreases in growth trajectory across weight, length, and head circumference. The simultaneous decrease suggests a role for altered growth regulation in children with CHD.


Initiator-elongator discrimination in vertebrate tRNAs for protein synthesis.
Initiator tRNAs are used exclusively for initiation of protein synthesis and not for the elongation step. We show, in vivo and in vitro, that the primary sequence feature that prevents the human initiator tRNA from acting in the elongation step is the nature of base pairs 50:64 and 51:63 in the TpsiC stem of the initiator tRNA. Various considerations suggest that this is due to sequence-dependent perturbation of the sugar phosphate backbone in the TpsiC stem of initiator tRNA, which most likely blocks binding of the elongation factor to the tRNA. Because the sequences of all vertebrate initiator tRNAs are identical, our findings with the human initiator tRNA are likely to be valid for all vertebrate systems. We have developed reporter systems that can be used to monitor, in mammalian cells, the activity in elongation of mutant human initiator tRNAs carrying anticodon sequence mutations from CAU to CCU (the C35 mutant) or to CUA (the U35A36 mutant). Combination of the anticodon sequence mutation with mutations in base pairs 50:64 and 51:63 yielded tRNAs that act as elongators in mammalian cells. Further mutation of the A1:U72 base pair, which is conserved in virtually all eukaryotic initiator tRNAs, to G1:C72 in the C35 mutant background yielded tRNAs that were even more active in elongation. In addition, in a rabbit reticulocyte in vitro protein-synthesizing system, a tRNA carrying the TpsiC stem and the A1:U72-to-G1:C72 mutations was almost as active in elongation as the elongator methionine tRNA. The combination of mutant initiator tRNA with the CCU anticodon and the reporter system developed here provides the first example of missense suppression in mammalian cells.


Monitoring virological responses to interferon-ribavirin and interferon monotherapy of chronic hepatitis C re-treated due to relapse or non-response.
Adding the nucleoside analog ribavirin (RBV) to interferon (IFN) for treatment of HCV has improved the sustained response rates, but the mechanism by which RBV mediates viral clearance is not fully understood. In this study, a highly sensitive method (Codes Amplicor HCV Monitor) was used to monitor the early (first 12 weeks of therapy) and long-term virological response in 20 patients who were treated first with IFN and later, due to non-sustained response, with IFN-RBV. All 10 IFN relapsers displayed a prompt virological response at week 4 to both IFN and IFN-RBV therapy; nine of them showed a sustained response to IFN-RBV. Out of 10 IFN non-responders, five showed a sustained response to IFN-RBV. Four of these were HCV RNA-negative at week 4 of IFN-RBV therapy and two of them had a transient early virological response (RNA-negative at weeks 4-8) to IFN alone. Overall, of the 14 patients (nine IFN relapsers, five IFN non-responders) with a sustained response to IFN-RBV, 11 and 13 had HCV RNA below 2000 copies/ml at week 4 of IFN and IFN-RBV, respectively, as compared with one and one of six patients without a sustained response to IFN-RBV (p < 0.02). Thus, addition of RBV to IFN increased both viral clearance during the first 12 weeks of therapy and the rate of sustained response. Loss of viremia at week 4 of IFN was associated with a sustained response to IFN-RBV and was seen in 11 of 13 patients (85%) with genotypes 2 or 3, as compared with one of seven patients (14%) with genotype 1 (p = 0.0044).


[Effect of oligoribonucleotides specifically bound by E. coli RNA-polymerase on DNA-dependent RNA synthesis].
It was shown previously that E. coli RNA-polymerase (EC 184.108.40.206) selectively binds certain fractions of penta- or hexaribonucleotides random mixtures (Knorre V. L., Vasilenko S. V., Salganik R. I., FEBS Lett., 30, 229, 1973). The data obtained demonstrate that such oligoribonucleotides compete with DNA for the RNA polymerase active centre and inhibit DNA dependent RNA synthesis catalyzed by the enzyme. These properties are absent in tri- and tetraribonucleotides which cannot be bound by RNA polymerase. The inhibitory action of the pentaribonucleotides was higher when they had been added prior to DNA to the mixture containing RNA polymerase.


Letters to the editor in response to studies of guns in the home and homicide and suicide.
Letters to the editor are an important venue for scientific discussion and ensuring accountability of authors and editors. We investigated the content and tone of letters to the editor published in response to research on having a firearm in the home as it relates to homicide and suicide. A recent meta-analysis found 16 analytic studies of household firearm access and homicide and suicide. We audited the letters to the editor emanating from those 16 articles. Each letter was coded for themes by two raters and analyzed using descriptive statistics and cluster analysis. For comparison, we also coded and analyzed the content of letters to the editor written in response to all other articles that were published in the same journal volumes where the firearm articles appeared. We identified 30 letters regarding the gun in the home studies: 24 (80%) letters to the editor and 6 (20%) replies from original authors. Of the 24 letters to the editor, 30% contained no scientific discussion, 46% made a political reference, 17% criticized the original author's character, and 25% criticized the journal. Moreover, 29% made a pro-gun reference, 25% made an anti-gun reference, 13% referred to the constitutional right to bear arms, 13% referred to the National Rifle Association (NRA), and 0% referred to advocacy organizations known to be in opposition to the NRA. Of these themes mentioned in letters to the editor, only the NRA was mentioned in a response by an original author. The median number of scientific citations in letters to the editor was one versus four in replies from original authors. In the articles on topics other than firearms that were analyzed as a point of comparison, only 8% contained no scientific discussion, 4% made a political reference, 2% criticized the authors' character, and 0% criticized the journal. Letters to the editor in response to epidemiologic research on guns in the home contain considerable content that minimally advances scientific discussion; author responses meet a higher standard for science and civility, as do letters to the editor regarding research topics other than firearms. The scientific study of firearm violence could be better served with more letters containing greater scientific commentary and dissent.


Suppressors of the organ-specific differentiation gene pha-1 of Caenorhabditis elegans.
The embryonic lethal gene pha-1 of the nematode Caenorhabditis elegans is required for late differentiation and morphogenesis of the pharynx in the developing embryo. Revertants of two temperature-sensitive alleles of pha-1 were isolated with the aim of obtaining mutations in genes that interact with pha-1. By various methods of mutagenesis, chemical, X-ray, transposon, or by spontaneous reversion, 220 recessive revertants were obtained, defining three complementation groups. The largest, sup-35 on linkage group (LG) III, maps close to but is separable from pha-1. This suppressor can exert its effect either maternally or zygotically to allow survival of pha-1(ts) embryos. The other two, sup-36 and sup-37, are required zygotically and map on LGIV and LGV, respectively. We have not noted a phenotype distinguishing any of the suppressors from wild type except for suppression of pha-1. That suppression is the null phenotype of at least sup-35 is indicated by the high frequency of mutation and by the fact that heterozygotes carrying sup-35 and a deficiency spanning the locus are also able to suppress. Five spontaneous mutations in sup-35 were found to be associated with recombination.


Global epidemiology of multiple birth.
Multiple births, which account for approximately 3% of births and 14% of infant deaths, are increasing in frequency. Multiple birth rates began to decline in the 1950s, reaching a minimum in the 1970s and rising since then. Both twin and triplet rates followed the same rising trend until 1998, after which triplet birth rates began to decline while twin birth rates continued to rise. Rising maternal age is associated with rising frequency of dizygotic twinning up to 37 years of age. Older maternal age, associated with the social trend to delayed child bearing, accounts for 25- 30% of the rise in multiple birth rates since 1970. The resulting rise in the prevalence of infertility has given rise to unprecedented use of ovarian stimulation treatments that stimulate the development of multiple oocytes. Assisted reproduction technology and ovulation stimulation with clomiphene citrate or gonadotrophins without assisted reproduction account for similar proportions of both twin births (20- 30%) and triplet births (30- 40%). The fall in triplet rates since 2000 is reassuring, but fetal reduction of high order pregnancies may be a factor in rising twin rates. Continuing attention is needed to all possible means of minimizing triplet pregnancies.


Side match and overlap match vector quantizers for images.
A class of vector quantizers with memory that are known as finite state vector quantizers (FSVQs) in the image coding framework is investigated. Two FSVQ designs, namely side match vector quantizers (SMVQs) and overlap match vector quantizers (OMVQs), are introduced. These designs take advantage of the 2-D spatial contiguity of pixel vectors as well as the high spatial correlation of pixels in typical gray-level images. SMVQ and OMVQ try to minimize the granular noise that causes visible pixel block boundaries in ordinary VQ. For 512 by 512 gray-level images, SMVQ and OMVQ can achieve communication quality reproduction at an average of 1/2 b/pixel per image frame, and acceptable quality reproduction. Because block boundaries are less visible, the perceived improvement in quality over ordinary VQ is even greater. Owing to the structure of SMVQ and OMVQ, simple variable length noiseless codes can achieve as much as 60% bit rate reduction over fixed-length noiseless codes.


Administration of four-factor prothrombin complex concentrate for a life-threatening bleed in a Jehovah's Witness patient.
: Life-threatening bleeds are medical emergencies that require time-sensitive decision making. Patients of the Jehovah's Witness faith can present a challenging conundrum when their beliefs conflict with modern treatment options for haemorrhage. Providers may not be aware of the grades of acceptance of the newer products outside of packed red blood cells. Researchers present a case of using four-factor prothrombin complex concentrate in a Jehovah's Witness patient in a life-threatening gastrointestinal haemorrhage along with a brief review of the literature.


Advance Care Planning and Care Coordination for People With Parkinson's Disease and Their Family Caregivers-Study Protocol for a Multicentre, Randomized Controlled Trial.
Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with motor- and non-motor symptoms. When the disease progresses, symptom burden increases. Consequently, additional care demands develop, the complexity of treatment increases, and the patient's quality of life is progressively threatened. To address these challenges, there is growing awareness of the potential benefits of palliative care for people with PD. This includes communication about end-of-life issues, such as Advance Care Planning (ACP), which helps to elicit patient's needs and preferences on issues related to future treatment and care. In this study, we will assess the impact and feasibility of a nurse-led palliative care intervention for people with PD across diverse European care settings. Methods: The intervention will be evaluated in a multicentre, open-label randomized controlled trial, with a parallel group design in seven European countries (Austria, Estonia, Germany, Greece, Italy, Sweden and United Kingdom). The "PD_Pal intervention" comprises (1) several consultations with a trained nurse who will perform ACP conversations and support care coordination and (2) use of a patient-directed "Parkinson Support Plan-workbook". The primary endpoint is defined as the percentage of participants with documented ACP-decisions assessed at 6 months after baseline (t1). Secondary endpoints include patients' and family caregivers' quality of life, perceived care coordination, patients' symptom burden, and cost-effectiveness. In parallel, we will perform a process evaluation, to understand the feasibility of the intervention. Assessments are scheduled at baseline (t0), 6 months (t1), and 12 months (t2). Statistical analysis will be performed by means of Mantel-Haenszel methods and multilevel logistic regression models, correcting for multiple testing. Discussion: This study will contribute to the current knowledge gap on the application of palliative care interventions for people with Parkinson's disease aimed at ameliorating quality of life and managing end-of-life perspectives. Studying the impact and feasibility of the intervention in seven European countries, each with their own cultural and organisational characteristics, will allow us to create a broad perspective on palliative care interventions for people with Parkinson's disease across settings. Clinical Trial Registration:www.trialregister.nl, NL8180.


Blurring contact maps of thousands of proteins: what we can learn by reconstructing 3D structure.
The present knowledge of protein structures at atomic level derives from some 60,000 molecules. Yet the exponential ever growing set of hypothetical protein sequences comprises some 10 million chains and this makes the problem of protein structure prediction one of the challenging goals of bioinformatics. In this context, the protein representation with contact maps is an intermediate step of fold recognition and constitutes the input of contact map predictors. However contact map representations require fast and reliable methods to reconstruct the specific folding of the protein backbone. In this paper, by adopting a GRID technology, our algorithm for 3D reconstruction FT-COMAR is benchmarked on a huge set of non redundant proteins (1716) taking random noise into consideration and this makes our computation the largest ever performed for the task at hand. We can observe the effects of introducing random noise on 3D reconstruction and derive some considerations useful for future implementations. The dimension of the protein set allows also statistical considerations after grouping per SCOP structural classes. All together our data indicate that the quality of 3D reconstruction is unaffected by deleting up to an average 75% of the real contacts while only few percentage of randomly generated contacts in place of non-contacts are sufficient to hamper 3D reconstruction.


The Efficacy of Pivotal Response Treatment in Teaching Question-Asking Initiations to Young Turkish Children with Autism Spectrum Disorder.
In the present study, a concurrent multiple baseline design across participants was used to evaluate the efficacy of pivotal response treatment (PRT) on the acquisition, maintenance, and generalization of the question-asking initiations by four children with autism spectrum disorder (ASD). The researchers also examined whether the implementation of PRT resulted in collateral changes in language development and other areas of development. The results of this study indicate that PRT is highly effective in teaching question-asking initiations. Participating children with ASD were able to generalize in natural settings and maintain long-term question-asking initiations. Furthermore, PRT resulted in positive collateral changes in language and other areas of development. Implications for future research and practice are then discussed.


Alpha-oxoaldehyde metabolism and diabetic complications.
The factors responsible for variable susceptibility to diabetic nephropathy are not clear. According to the non-enzymatic glycation hypothesis, diabetes-related tissue damage occurs due to a complex mixture of toxic products, including alpha-oxoaldehydes, which are inherently toxic as well as serving as precursors for advanced glycation end-products. Protective mechanisms exist to control this unavoidable glycation, and these are determined by genetic or environmental factors that can regulate the concentrations of the reactive sugars or end-products. In diabetes these protective mechanisms become more important, since glycation stress increases, and less efficient defence systems against this stress could lead to diabetic complications. Some of these enzymatic control mechanisms, including those that regulate alpha-oxoaldehydes, have been identified. We have observed significant increases in production of the alpha-oxoaldehydes methylglyoxal and 3-deoxyglucosone in three human populations with biopsy-proven progression of nephropathy. The increase in methylglyoxal could be secondary to defects in downstream glycolytic enzymes (such as glyceraldehyde-3-phosphate dehydrogenase) that regulate its production, or in detoxification mechanisms such as glyoxalase. Other mechanisms, however, appear to be responsible for the observed increase in 3-deoxyglucosone levels. We present results of our studies on the mechanisms responsible for variable production of alpha-oxoaldehydes by measuring the activity and characteristics of these enzymes in cells from complication-prone and -resistant diabetic patients. New therapeutic interventions designed to control these endogenous mechanisms could potentially enhance protection against excessive glycation and prevent or reverse complications of long-term diabetes.


Mesenteric lymphography and ligation of the thoracic duct in a cat with chylothorax.
Mesenteric lymphography was used to identify and ligate the thoracic duct in a 1-year-old Himalayan cat with chylothorax. Lymphography revealed the thoracic duct to be intact; however, multiple dilated lymphatics, indicative of lymphangiectasia were evident in the cranial portion of the thorax. Hemostatic clips were used to ligate the thoracic duct. The effusion stopped, and 9 months after surgery, effusion has not recurred.


Adrenomedullin Ameliorates Pulmonary Fibrosis by Regulating TGF-ß-Smads Signaling and Myofibroblast Differentiation.
Pulmonary fibrosis is an irreversible, potentially fatal disease. Adrenomedullin (AM) is a multifunctional peptide whose activity is regulated by receptor activity-modifying protein 2 (RAMP2). In the present study, we used the bleomycin (BLM)-induced mouse pulmonary fibrosis model to investigate the pathophysiological significance of the AM-RAMP2 system in the lung. In heterozygous AM knockout mice (AM+/-), hydroxyproline content and Ashcroft scores reflecting the fibrosis severity were significantly higher than in wild-type mice (WT). During the acute phase after BLM administration, FACS analysis showed significant increases in eosinophil, monocyte, and neutrophil infiltration into the lungs of AM+/-. During the chronic phase, fibrosis-related molecules were upregulated in AM+/-. Notably, nearly identical changes were observed in RAMP2+/-. AM administration reduced fibrosis severity. In the lungs of BLM-administered AM+/-, the activation level of Smad3, a receptor-activated Smad, was higher than in WT. In addition, Smad7, an antagonistic Smad, was downregulated and microRNA-21, which targets Smad7, was upregulated compared to WT. Isolated AM+/- lung fibroblasts showed less proliferation and migration capacity than WT fibroblasts. Stimulation with TGF-β increased the numbers of α-SMA-positive myofibroblasts, which were more prominent among AM+/- cells. TGF-β-stimulated AM+/- myofibroblasts were larger and exhibited greater contractility and extracellular matrix production than WT cells. These cells were α-SMA (+), F-actin (+), and Ki-67(-) and appeared to be nonproliferating myofibroblasts (non-p-MyoFbs), which contribute to the severity of fibrosis. Our findings suggest that in addition to suppressing inflammation, the AM-RAMP2 system ameliorates pulmonary fibrosis by suppressing TGF-β-Smad3 signaling, microRNA-21 activity and differentiation into non-p-MyoFbs.


Health professionals' and dietetics practitioners' perceived effectiveness of fruit and vegetable parenting practices across six countries.
Fruit and vegetable intake may reduce the risk of some chronic diseases. However, many children consume less-than-recommended amounts of fruit and vegetables. Because health professionals and dietetics practitioners often work with parents to increase children's fruit and vegetable intake, assessing their opinions about the effectiveness of parenting practices is an important step in understanding how to promote fruit and vegetable intake among preschool-aged children. Using a cross-sectional design, collaborators from six countries distributed an Internet survey to health and nutrition organization members. A self-selected sample reported their perceptions of the effectiveness of 39 parenting practices intended to promote fruit and vegetable consumption in preschool-aged children from May 18, 2008, to September 16, 2008. A total of 889 participants (55% United States, 22.6% Mexico, 10.9% Australia, 4.4% Spain, 3.3% Chile, 2.2% United Kingdom, and 1.6% other countries) completed the survey. The fruit and vegetable intake-related parenting practices items were categorized into three dimensions (structure, responsiveness, and control) based on a parenting theory conceptual framework and dichotomized as effective/ineffective based on professional perceptions. The theoretically derived factor structures for effective and ineffective parenting practices were evaluated using separate confirmatory factor analyses and demonstrated acceptable fit. Fruit and vegetable intake-related parenting practices that provide external control were perceived as ineffective or counterproductive, whereas fruit and vegetable intake-related parenting practices that provided structure, nondirective control, and were responsive were perceived as effective in getting preschool-aged children to consume fruit and vegetables. Future research needs to develop and validate a parent-reported measure of these fruit and vegetable intake-related parenting practices and to empirically evaluate the effect of parental use of the parenting practices on child fruit and vegetable consumption.


Immobilization of polymer-decorated liquid crystal droplets on chemically tailored surfaces.
We demonstrate that the assembly of an amphiphilic polyamine on the interfaces of micrometer-sized droplets of a thermotropic liquid crystal (LC) dispersed in aqueous solutions can be used to facilitate the immobilization of LC droplets on chemically functionalized surfaces. Polymer 1 was designed to contain both hydrophobic (alkyl-functionalized) and hydrophilic (primary and tertiary amine-functionalized) side chain functionality. The assembly of this polymer at the interfaces of aqueous dispersions of LC droplets was achieved by the spontaneous adsorption of polymer from aqueous solution. Polymer adsorption triggered transitions in the orientational ordering of the LCs, as observed by polarized light and bright-field microscopy. We demonstrate that the presence of polymer 1 on the interfaces of these droplets can be exploited to immobilize LC droplets on planar solid surfaces through covalent bond formation (e.g., for surfaces coated with polymer multilayers containing reactive azlactone functionality) or through electrostatic interactions (e.g., for surfaces coated with multilayers containing hydrolyzed azlactone functionality). The characterization of immobilized LC droplets by polarized, fluorescence, and laser scanning confocal microscopy revealed the general spherical shape of the polymer-coated LC droplets to be maintained after immobilization, and that immobilization led to additional ordering transitions within the droplets that were dependent on the nature of the surfaces with which they were in contact. Polymer 1-functionalized LC droplets were not immobilized on polymer multilayers treated with poly(ethylene imine) (PEI). We demonstrate that the ability to design surfaces that promote or prevent the immobilization of polymer-functionalized LC droplets can be exploited to pattern the immobilization of LC droplets on surfaces. The results of this investigation provide the basis of an approach that could be used to tailor the properties of dispersed LC emulsions and to immobilize these droplets on functional surfaces of interest in a broad range of fundamental and applied contexts.


The Neutrophil's Choice: Phagocytose vs Make Neutrophil Extracellular Traps.
Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, thus modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be "poised" in an unresponsive state. Environmental conditions, the metabolic, adhesive and activation state of the phagocyte, and the size of and signals associated with the tethered phagocytic cargo influence the choice of the neutrophils, prompting either phagocytic clearance or the generation of NETs. The choice is dichotomic and apparently irreversible. Defects in phagocytosis may foster the intravascular generation of NETs, thus promoting vascular inflammation and morbidities associated with diseases characterized by defective phagocytic clearance, such as systemic lupus erythematosus. There is a strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes.


In vitro synergistic activities of cefazolin and nisin A against mastitis pathogens.
First-generation cephalosporins such as cefazolin (CEZ) have been widely used for mastitis treatment in dairy cattle. However, the use of antibiotics results in the presence of antibiotic residues in milk, which is used for human consumption. Nisin A, a bacteriocin produced by Lactococcus lactis, has been used as a broad-spectrum food preservative for over 50 years. Therefore, a combination of CEZ and nisin A might provide an extended activity spectrum against mastitis pathogens and reduce the antibiotic dose for mastitis treatment. This study aimed to evaluate the combined effect of CEZ and nisin A against mastitis pathogens using the checkerboard and time-kill assays. In the checkerboard assay, the CEZ-nisin A combination exhibited a synergistic effect against Staphylococcus aureus (n=20/20) and Enterococcus faecalis (n=13/18), and meanwhile exhibited a mostly additive effect against Staphylococcus intermedius (n=12/20), Streptococcus agalactiae (n=10/10), Streptococcus dysgalactiae (n=18/18), and Escherichia coli (n=14/18). There were no indifferent or antagonistic effects between CEZ and nisin A. In the time-kill assay, the CEZ-nisin A combination at 0.5 × or 1 × minimum inhibitory concentration exhibited synergistic reduction of bacterial growth by over 3 log10 colony forming units per ml relative to that observed with either antimicrobial substance alone. These results suggest that the CEZ-nisin A combination can be used for developing an intramammary infusion for mastitis treatment, with lower antibiotic concentrations than normal.


Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy.
Tumor-endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their "crosstalk" with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluated the in vitro and in vivo synergistic and/or additive effects of a combination of conditional oncolytic adenovirus plus an adenoviral-mediated antiangiogenic therapy. In the in vitro study, we demonstrated that human umbilical vein endothelial cells (HUVEC) and human C4-2 androgen-independent (AI) prostate cancer cells, when infected with an antiangiogenic adenoviral (Ad)-Flk1-Fc vector secreting a soluble form of Flk1, showed dramatically inhibited proliferation, migration and tubular formation of HUVEC endothelial cells. C4-2 cells showed maximal growth inhibition when coinfected with Ad-Flk1-Fc and Ad-hOC-E1, a conditional replication-competent Ad vector with viral replication driven by a human osteocalcin (hOC) promoter targeting both prostate cancer epithelial and stromal cells. Using a three-dimensional (3D) coculture model, we found that targeting C4-2 cells with Ad-hOC-E1 markedly decreased tubular formation in HUVEC, as visualized by confocal microscopy. In a subcutaneous C4-2 tumor xenograft model, tumor volume was decreased by 40-60% in animals treated with Ad-Flk1-Fc or Ad-hOC-E1 plus vitamin D3 alone and by 90% in a combined treatment group, compared to untreated animals in an 8-week treatment period. Moreover, three of 10 (30%) pre-established tumors completely regressed when animals received combination therapy. Cotargeting tumor and tumor endothelium could be a promising gene therapy strategy for the treatment of both localized and metastatic human prostate cancer.


[Individual features of rat behavior: manifestations of anxiety].
Motor agitation developing in some white rats during painful stimulation of other individual decreases under the action of phenasepam (the most effective drug used in clinic in cases of neurotic alarm). This effect is accompanied by strengthening of tendency to reside in closed space. After phenasepam injection, increased not goal-directed motor activity developing against the background of reduced alimentary reactions also decreases in a part of grey rats selected by their ability to extrapolate, while their alimentary behaviour intensifies. Thus, initial peculiarities of behaviour i.e. enhanced motor activity not directed to fulfillment of the above forms of inborn behaviour (residing in closed space and eating) may be considered as a manifestation of anxiety. In this case, these forms of behaviour have a defensive function.


Use of plasmid profiles in epidemiologic surveillance of disease outbreaks and in tracing the transmission of antibiotic resistance.
Plasmids are circular deoxyribonucleic acid molecules that exist in bacteria, usually independent of the chromosome. The study of plasmids is important to medical microbiology because plasmids can encode genes for antibiotic resistance or virulence factors. Plasmids can also serve as markers of various bacterial strains when a typing system referred to as plasmid profiling, or plasmid fingerprinting is used. In these methods partially purified plasma deoxyribonucleic acid species are separated according to molecular size by agarose gel electrophoresis. In a second procedure, plasmid deoxyribonucleic acid which has been cleaved by restriction endonucleases can be separated by agarose gel electrophoresis and the resulting pattern of fragments can be used to verify the identity of bacterial isolates. Because many species of bacteria contain plasmids, plasmid profile typing has been used to investigate outbreaks of many bacterial diseases and to trace inter- and intra-species spread of antibiotic resistance.


Injectable hydrogel-incorporated cancer cell-specific cisplatin releasing nanogels for targeted drug delivery.
Cisplatin (CDDP) is a well-known anticancer agent, and it has been widely used to treat various solid tumors during clinical cancer therapy. Nevertheless, therapeutic applications of CDDP are hampered by its severe side effects. Although CDDP can be encapsulated into nano-scale drug delivery formulations to improve its physicochemical properties, the lack of stability in the formulation and cancer cell-specific targetability have prompted the exploration of novel vectors for the targeted delivery of CDDP. Here, we introduce CDDP-bearing chondroitin sulfate nanogels (CS-nanogels) that are synthesized through a chelating ligand-metal coordination cross-linking reaction, and then incorporated into pH- and temperature-responsive bioresorbable poly(ethylene glycol)-poly(β-aminoester urethane) (PEG-PAEU) hydrogels for cancer cell-specific delivery of CDDP. The CS-nanogels released from the hydrogels exhibit a pH-dependent release of CDDP. CDDP was released slowly under physiological conditions (pH 7.4), whereas the release of CDDP was triggered under acidic conditions (pH 5.0). Confocal microscopy images demonstrated that fluorescein-5-thiosemicarbazide-labeled CS-nanogels released from the hydrogels selectively bound to the A549 lung carcinoma cell line through the overexpressing CD44 receptor but not to NIH 3T3 cells. An in vitro cytotoxicity test indicated that CS-nanogels released from the hydrogels effectively inhibited the growth of A549 lung carcinoma cells. Subcutaneous injection of CS-nanogel-loaded PEG-PAEU copolymer sols into the dorsal region of Sprague-Dawley rats spontaneously formed a viscoelastic gel without causing noticeable inflammation at the injection site and was found to be bioresorbable in eight weeks. Overall, the injectable hydrogel-incorporated CS-nanogels were demonstrated to be a useful formulation for the targeted delivery of CDDP.


Where Are They Now? Evolution of a Nurse Anesthesia Training School in Ghana and a Survey of Graduates.
Ghana, like other countries in sub-Saharan African, has limited access to surgery. One contributing factor is the inadequate number of anesthesia providers. To address this need, Kybele, Inc., a US-based non-governmental organization, partnered with the Ghana Health Service to establish the third nurse anesthesia training school (NATS) in Ghana. The school, based at Ridge Regional Hospital (RRH) in Accra, opened in October 2009. This paper describes the evolution of the training program and presents the curriculum. Second, the results of a voluntary survey conducted among the first four classes of graduates (2011-2014) are presented to determine their perceived strengths and gaps in training and to identify employment locations and equipment availability. Seventy-five of 93 graduates (81%) responded to the survey. The graduates reported working in 39 hospitals across 7 of the 10 regions in Ghana. Six providers (8%) worked alone and 16 (21%) were one of only two providers. Fifty-three providers (71%) had no physician anesthesiologist at their facility. Most providers had access to basic anesthesia equipment; however, there was limited access to emergency airway equipment. While most graduates felt that their training had prepared them for their current positions, 21% reported experiencing a patient death during anesthesia. The NATS at RRH has been sustained and most of the graduates are working in Ghana, filling an important void. Quality improvement and continuing education must be emphasized in an effort to reduce surgical morbidity and mortality in Ghana.


Laparoscopic gastric bypass complicated by portal venous thrombosis and severe neurological complications.
The laparoscopic Roux-en-Y gastric bypass (LRYGBP) is increasingly popular for the treatment of morbid obesity, although its postsurgical complications are often underestimated. We report the case of a 22-year-old morbidly obese woman who underwent a LRYGBP, which was rapidly complicated by portal venous thrombosis and severe neurological complications due to vitamin deficiencies. She presented rapid body weight loss with optic and peripheral neuropathy. Clinical chemistry results showed low transthyretin and micronutrient levels. Intravenous micronutrient infusion and cyclic nocturnal enteral tube feeding were needed to slowly improve gait and visual acuity. We then discuss (1) factors that could have contributed to the nutritional deficiencies and (2) the preventive management of these types of nutritional complications. Gastric bypass procedures can cause multivitamin deficiencies. In the case presented here, complications occurred very soon after surgery. The increasing incidence of obesity and bariatric surgery warrants better patient education concerning strict adherence to vitamin supplementation.


Economic burden of attention-deficit/hyperactivity disorder among children and adolescents in the United States: a societal perspective.
To provide a comprehensive evaluation of the economic burden associated with attention-deficit/hyperactivity disorder (ADHD) among children and adolescents from a US societal perspective. Direct healthcare costs of children (5-11 years) and adolescents (12-17 years) with ADHD were obtained using claims data from the IBM MarketScan Research Databases (01/01/2017-12/31/2018). Direct non-healthcare and indirect costs were estimated based on literature and government publications. Each cost component was estimated using a prevalence-based approach, with per-patient costs extrapolated to the national level. The total annual societal excess costs associated with ADHD were estimated at $19.4 billion among children ($6,799 per child) and $13.8 billion among adolescents ($8,349 per adolescent). Education costs contributed to approximately half of the total excess costs in both populations ($11.6 billion [59.9%] in children; $6.7 billion [48.8%] in adolescents). Other major contributors to the overall burden were direct healthcare costs ($5.0 billion [25.9%] in children; $4.0 billion [29.0%] in adolescents) and caregiving costs ($2.7 billion [14.1%] in children; $1.6 billion [11.5%] in adolescents). Cost estimates were calculated based on available literature and/or governmental publications due to the absence of a single data source for all costs associated with ADHD. Thus, the quality of cost estimates is limited by the accuracy of available data as well as the study populations and methodologies used by different studies. ADHD in children and adolescents is associated with a substantial economic burden that is largely driven by education costs, followed by direct healthcare costs and caregiver costs. Improved intervention strategies and policies may reduce the clinical and economic burden of ADHD in these populations.


Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.
C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity, diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol, and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial, anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.


Bead-Based Hydrodynamic Simulations of Rigid Magnetic Micropropellers.
The field of synthetic microswimmers, micro-robots moving in aqueous environments, has evolved significantly in the last years. Micro-robots actuated and steered by external magnetic fields are of particular interest because of the biocompatibility of this energy source and the possibility of remote control, features suited for biomedical applications. While initial work has mostly focused on helical shapes, the design space under consideration has widened considerably with recent works, opening up new possibilities for optimization of propellers to meet specific requirements. Understanding the relation between shape on the one hand and targeted actuation and steerability on the other hand requires an understanding of their propulsion behavior. Here we propose hydrodynamic simulations for the characterization of rigid micropropellers of any shape, actuated by rotating external magnetic fields. The method consists of approximating the propellers by rigid clusters of spheres. We characterize the influence of model parameters on the swimming behavior to identify optimal simulation parameters using helical propellers as a test system. We then explore the behavior of randomly shaped propellers that were recently characterized experimentally. The simulations show that the orientation of the magnetic moment with respect to the propeller's internal coordinate system has a strong impact on the propulsion behavior and has to be known with a precision of ≤ 5° to predict the propeller's velocity-frequency curve. This result emphasizes the importance of the magnetic properties of the micropropellers for the design of desired functionalities for potential biomedical applications, and in particular the importance of their orientation within the propeller's structure.


Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium.
There is evidence for hormonal receptor desensitisation in human myometrium, but little is known about the mechanisms involved in the loss of myometrial response to agonists such as beta(2)-adrenergic agonists, prostaglandin gamma and oxytocin. It is well known that the receptors for these hormones are coupled to G-proteins. The first step of receptor desensitisation is the phosphorylation of activated receptors by a G-protein-coupled receptor kinase (GRK). GRKs are members of a multigene family and the various subtypes differ in their localisation, regulation and mode of action. We have used Western blotting and reverse transcription PCR to identify the GRKs present in human myometrium from pregnant and non-pregnant women as well as in cultured human myometrial cells. We have found that human myometrium expresses the GRK subtypes 2, 4gamma, 5 and 6. On the other hand, GRK3 and the isoforms GRK4alpha, beta and delta were not found in myometrial tissue. Our data indicate that GRK2 is only expressed in pregnant term myometrium and is not found in non-pregnant tissue. Moreover, GRK6 appears to be expressed at a much higher level in pregnant term tissue than in non-pregnant myometrium. Our observations suggest that GRK2 and GRK6 may contribute to the regulation of uterine contractility at term. Further work is necessary to determine whether GRKs and receptor desensitisation play a role in disorders of uterine contractility.


Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt.
An eleven-year-old clinically dysmorphic and developmentally retarded male child presenting with complaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic portocaval shunt (Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were confirmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed.


The wide-angle equation and its solution through the short-time iterative Lanczos method.
Properties of the wide-angle equation (WAEQ), a nonparaxial scalar wave equation used to propagate light through media characterized by inhomogeneous refractive-index profiles, are studied. In particular, it is shown that the WAEQ is not equivalent to the more complicated but more fundamental Helmholtz equation (HEQ) when the index of refraction profile depends on the position along the propagation axis. This includes all nonstraight waveguides. To study the quality of the WAEQ approximation, we present a novel method for computing solutions to the WAEQ. This method, based on a short-time iterative Lanczos (SIL) algorithm, can be applied directly to the full three-dimensional case, i.e., systems consisting of the propagation axis coordinate and two transverse coordinates. Furthermore, the SIL method avoids series-expansion procedures (e.g., Padé approximants) and thus convergence problems associated with such procedures. Detailed comparisons of solutions to the HEQ, WAEQ, and the paraxial equation (PEQ) are presented for two cases in which numerically exact solutions to the HEQ can be obtained by independent analysis, namely, (i) propagation in a uniform dielectric medium and (ii) propagation along a straight waveguide that has been tilted at an angle to the propagation axis. The quality of WAEQ and PEQ, compared with exact HEQ results, is investigated. Cases are found for which the WAEQ actually performs worse than the PEQ.


A study of risk factors for infection with HPAI H5N1 in small poultry farms in Thailand using a questionnaire survey.
A questionnaire was used to collect data on small poultry farm management and wild bird observed in poultry keeping areas to identify putative risk factors for infection with HPAI H5N1. The study was conducted in 2008 in four subdistricts of central Thailand that had experienced outbreaks of HPAI H5N1 in poultry. Descriptive and inferential analyses including univariable analyses and multivariable logistic regression were used to identify putative risk factors. Risk factors included purchasing native chickens/fighting cocks from commercial hatcheries, replacing or restocking birds individually, and observing lesser whistling ducks (Dendrocygna javanica) on the farm daily. Selecting healthy animals when purchasing animals to ensure that they were disease free was a protective factor. To fully understand the epidemiology of infection of small poultry farms with HPAI H5N1, control of movement of domestic poultry and serological and virological testing of the poultry population should be applied.


Evolutionary Sample Size and Consilience in Phylogenetic Comparative Analysis.
Phylogenetic comparative methods (PCMs) are commonly used to study evolution and adaptation. However, frequently used PCMs for discrete traits mishandle single evolutionary transitions. They erroneously detect correlated evolution in these situations. For example, hair and mammary glands cannot be said to have evolved in a correlated fashion because each evolved only once in mammals, but a commonly used model (Pagel's Discrete) statistically supports correlated (dependent) evolution. Using simulations, we find that rate parameter estimation, which is central for model selection, is poor in these scenarios due to small effective (evolutionary) sample sizes of independent character state change. Pagel's Discrete model also tends to favor dependent evolution in these scenarios, in part, because it forces evolution through state combinations unobserved in the tip data. This model prohibits simultaneous dual transitions along branches. Models with underlying continuous data distributions (e.g., Threshold and GLMM) are less prone to favor correlated evolution but are still susceptible when evolutionary sample sizes are small. We provide three general recommendations for researchers who encounter these common situations: i) create study designs that evaluate a priori hypotheses and maximize evolutionary sample sizes; ii) assess the suitability of evolutionary models-for discrete traits, we introduce the phylogenetic imbalance ratio; and iii) evaluate evolutionary hypotheses with a consilience of evidence from disparate fields, like biogeography and developmental biology. Consilience plays a central role in hypothesis testing within the historical sciences where experiments are difficult or impossible to conduct, such as many hypotheses about correlated evolution. These recommendations are useful for investigations that employ any type of PCM. [Class imbalance; consilience; correlated evolution; evolutionary sample size; phylogenetic comparative methods.].


Risk factors and prediction of very short term versus short/intermediate term post-stroke mortality: a data mining approach.
Data mining and knowledge discovery as an approach to examining medical data can limit some of the inherent bias in the hypothesis assumptions that can be found in traditional clinical data analysis. In this paper we illustrate the benefits of a data mining inspired approach to statistically analysing a bespoke data set, the academic multicentre randomised control trial, U.K Glucose Insulin in Stroke Trial (GIST-UK), with a view to discovering new insights distinct from the original hypotheses of the trial. We consider post-stroke mortality prediction as a function of days since stroke onset, showing that the time scales that best characterise changes in mortality risk are most naturally defined by examination of the mortality curve. We show that certain risk factors differentiate between very short term and intermediate term mortality. In particular, we show that age is highly relevant for intermediate term risk but not for very short or short term mortality. We suggest that this is due to the concept of frailty. Other risk factors are highlighted across a range of variable types including socio-demographics, past medical histories and admission medication. Using the most statistically significant risk factors we build predictive classification models for very short term and short/intermediate term mortality.


What effects have resident work-hour changes had on education, quality of life, and safety? A systematic review.
More than 15 years ago, the Institute of Medicine (IOM) identified medical error as a problem worthy of greater attention; in the wake of the IOM report, numerous changes were made to regulations to limit residents' duty hours. However, the effect of resident work-hour changes remains controversial within the field of orthopaedics. We performed a systematic review to determine whether work-hour restrictions have measurably influenced quality-of-life measures, operative and technical skill development, resident surgical education, patient care outcomes (including mortality, morbidity, adverse events, sentinel events, complications), and surgeon and resident attitudes (such as perceived effect on learning and training experiences, personal benefit, direct clinical experience, clinical preparedness). We performed a systematic review of PubMed, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Google Scholar using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were any English language peer-reviewed articles that analyzed the effect(s) of orthopaedic surgery resident work-hour restrictions on patient safety, resident education, resident/surgeon quality of life, resident technical operative skill development, and resident surgeon attitudes toward work-hour restrictions. Eleven studies met study inclusion criteria. One study was a prospective analysis, whereas 10 studies were of level IV evidence (review of surgical case logs) or survey results. Within our identified studies, there was some support for improved resident quality of life, improved resident sleep and less fatigue, a perceived negative impact on surgical operative and technical skill, and conflicting evidence on the topic of resident education, patient outcomes, and variable attitudes toward the work-hour changes. There is a paucity of high-level or clear evidence evaluating the effect of the changes to resident work hours. Future research in this area should focus on objective measures that include patient safety as a primary outcome.