Trauma in the Russian Federation: then and now.
Russia has made substantial, largely unrecognized contributions to the field of trauma. These include the early development of triage, improvement of blood transfusions and blood bank networks, and Mobile Emergency Medical Services. Despite these advances, injury fatality rates in Russia are alarmingly high (∼50% higher than other Eastern European countries). They fluctuated dramatically during 1980 to 2006, a period that included the dissolution of Union of Soviet Socialist Republics. Suggested causes, including inaccurate data, alcohol use, and economic hardship, are investigated in this article. Injury mortality rates for homicide, suicide, accidental poisoning, and total injuries (source: World Health Organization), alcohol consumption (source: World Health Organization), and economic data (source: United Nations Economic Commission for Europe) for the Russian Federation from 1980 to 2006 were examined and compared with the Baltic States, Central Asian Republics, other Eastern European nations, and the United States. Injury mortality rates declined in Russia from 1980 to 1987. The total injury mortality rate more than doubled between 1987 and 1994, followed by a 40% decline from 1994 to 1998. The 1984 to 1994 mortality rates generally parallel alcohol consumption trends. The 1991 to 1994 climb coincides with the dissolution of the Union of Soviet Socialist Republics. A smaller rise in fatality rates occurred in the early 2000s. Deaths caused by injuries in the Russian Federation are related to multiple factors. Some authors conclude that the data accurately reflect injury mortality. Financial concerns during these times may have led to riskier behaviors resulting in more deaths from injuries. Heavy alcohol consumption also likely contributes to high injury mortality rates. Excessive injury mortality calls for action by Russian policy makers.


Association of early CT abnormalities, infarct size, and apparent diffusion coefficient reduction in acute ischemic stroke.
Diffusion-weighted (DW) imaging is more sensitive for early ischemia than CT, and apparent diffusion coefficient (ADC) mapping permits quantification of the severity of cytotoxic edema. We examined the relationship between early CT findings, ischemic lesion volume on DW images, and edema subtype. Patients in whom early signs of ischemia were detected on baseline CT scans were scored CT positive. Baseline DW lesion volumes were compared between the CT-positive and CT-negative patients. In CT-positive patients, we outlined the CT-positive part of the DW lesion and transferred these regions of interest to the corresponding DW sections. The ADC values of the outlined CT-positive areas were then compared with the ADC values of the CT-negative areas within patients. Lesions with significantly increased T2 hyperintensity were excluded to correct for the effect of early vasogenic edema on ADC measurements. Twenty-four patients with cerebral ischemia in whom both CT and DW imaging were performed within 8 hours of symptom onset were entered into the study. Patients with early CT signs of infarction (n = 12) had significantly larger DW lesion volumes than did patients without early CT abnormalities (mean volume, 62.8 versus 14.6 mL; P =. 002). In patients displaying early CT abnormalities, CT-positive regions of the DW lesion had lower relative ADC (rADC) values than did the CT-negative regions, when lesions with significant T2 hyperintensity were excluded (mean rADC, 0.65 versus 0.75; P =.037). These findings support the hypothesis that early CT signs of infarction indicate more extensive and severe cerebral ischemia, as reflected by lower ADC.


Morphology of Evaporating Sessile Microdroplets on Lyophilic Elliptical Patches.
The evaporation of droplets occurs in a large variety of natural and technological processes such as medical diagnostics, agriculture, food industry, printing, and catalytic reactions. We study the different droplet morphologies adopted by an evaporating droplet on a surface with an elliptical patch with a different contact angle. We perform experiments to observe these morphologies and use numerical calculations to predict the effects of the patched surfaces. We observe that tuning the geometry of the patches offers control over the shape of the droplet. In the experiments, the drops of various volumes are placed on elliptical chemical patches of different aspect ratios and imaged in 3D using laser scanning confocal microscopy, extracting the droplet's shape. In the corresponding numerical simulations, we minimize the interfacial free energy of the droplet, by employing Surface Evolver. The numerical results are in good qualitative agreement with our experimental data and can be used for the design of micropatterned structures, potentially suggesting or excluding certain morphologies for particular applications. However, the experimental results show the effects of pinning and contact angle hysteresis, which are obviously absent in the numerical energy minimization. The work culminates with a morphology diagram in the aspect ratio vs relative volume parameter space, comparing the predictions with the measurements.


Trends in malaria admissions at the Mbakong Health Centre of the North West Region of Cameroon: a retrospective study.
Malaria is the leading cause of death worldwide. It is urgent to assess the impact of interventions and scaled-up control efforts. Despite reported reduction in malaria prevalence in Africa, the trends in Cameroon are not yet fully understood. The aim of this study was to investigate the trends in malaria admissions among febrile patients seeking treatment over a seven-year period (2006-2012) in an endemic area in Cameroon, hypothesizing a declining trend. This period followed changes in malaria treatment policy. The objectives were to identify possible trends in malaria admissions and to evaluate the impact of changes to treatment guidelines on the prevalence. Data was collected through consultation and perusal of laboratory and prescription registers of the Mbakong Health Centre. Data analysis was conducted using SPSS and SAS Statistics. Analysis revealed that 4,230 febrile patients were received from 2006-2012. Of these febrile cases, 29.30% were confirmed positive. Between 2006 and 2012 confirmed malaria positive cases of those tested fluctuated, dropping from 53.21% in 2006 to 17.20% in 2008; then rising to 35.00% in 2011 and, finally, dropping to 18.2% of those tested in 2012. The prevalence in females and males across all age groups were similar: a slightly higher risk of males to have malaria (OR = 1.08, 95% CI 0.94-1.25) were not practically significant. Of those tested, the 5 to < 15 years and the 1 to < 5 years age groups were the hardest hit by malaria in the area. A practically visible and significant association was observed between the age and gender with regards to the number of malaria positive results (Pearson ×2 = 153.675, p < 0.00001, Cramer's V = 0.352). Malaria prevalence exhibited a fluctuating yet declining trend, as observed over the 28 quarters between January, 2006 and December, 2012. The changes to the treatment guidelines appear to result in a declining trend as was observed between 2006 and 2008. However, malaria admissions fluctuated between 2008 and 2012. There is, therefore, a need to step up control efforts of especially the vulnerable groups, such as the very young.


An exploratory, comparative study investigating attrition and retention of student midwives.
to explore the retention and attrition of pre-registration midwifery students. an exploratory, comparative design that enabled the comparison of a 3-year and a 78-week midwifery programme. The methodology was designed into two main phases using both quantitative and qualitative methodology. a university in the South West of England. 36 questionnaires were sent to students who had left the programmes during 2001-2003. A purposive sample of 16 student midwives formed two separate focus groups. The participants were selected from current 3-year and 78-week midwifery programmes. midwifery attracts highly motivated students. In order for this motivation to continue through an emotional and demanding programme of study, their motivation needs to be nurtured and retained. The findings of this study clearly illustrate that in only a few cases can one over-riding reason be given for students withdrawing from midwifery programmes. there is often a complexity of 'personal reasons' and an accumulation of clinical and theoretical demands as to why students leave. Although there were realistic expectations of the programmes, the lived experiences of these expectations created anxiety and tension. It is therefore imperative that clinicians and academics work in harmony to plan and offer a programme of adequate mentorship and support for student midwives. This should also acknowledge the uniqueness of the different programmes that lead to qualification as a midwife.


The effect of correlation and false negatives in pool testing strategies for COVID-19.
During the current COVID-19 pandemic, active testing has risen as a key component of many response strategies around the globe. Such strategies have a common denominator: the limited availability of diagnostic tests. In this context, pool testing strategies have emerged as a means to increase testing capacity. The efficiency gains obtained by using pool testing, derived from testing combined samples simultaneously, vary according to the spread of the SARS-CoV-2 virus in the population being tested. Motivated by the need for testing closed populations, such as long-term care facilities (LTCFs), where significant correlation in infections is expected, we develop a probabilistic model for settings where the test results are correlated, which we use to compute optimal pool sizes in the context of two-stage pool testing schemes. The proposed model incorporates the specificity and sensitivity of the test, which makes it possible to study the impact of these measures on both the expected number of tests required for diagnosing a population and the expected number and variance of false negatives. We use our experience implementing pool testing in LTCFs managed by SENAMA (Chile's National Service for the Elderly) to develop a simulation model of contagion dynamics inside LTCFs, which incorporates testing and quarantine policies implemented by SENAMA. We use this simulation to estimate the correlation of test results among collected samples when following SENAMA's testing guidelines. Our results show that correlation estimates are high in settings representative of LTCFs, which validates the use of the proposed model for incorporating correlation in determining optimal pool sizes for pool testing strategies. Generally, our results show that settings in which pool testing achieves efficiency gains, relative to individual testing, are likely to be found in practice. Moreover, the results show that incorporating correlation in the analysis of pool testing strategies both improves the expected efficiency and broadens the settings in which the technique is preferred over individual testing.


Regulation of the Aurora-A gene following topoisomerase I inhibition: implication of the Myc transcription factor.
During the G2 phase of the cell cycle, the Aurora-A kinase plays an important role in centrosome maturation and progression to mitosis. In this study, we show in colorectal cell lines that Aurora-A expression is downregulated in response to topoisomerase I inhibition. Using chromatin immunoprecipitation assays, we have observed that the Myc transcription factor and its Max binding partner are associated with the Aurora-A promoter during the G2 phase of the cell cycle. RNA interference experiments indicated that Myc is involved in the regulation of the Aurora-A gene. Following topoisomerase I inhibition, the expression of Myc decreased whereas Mad was upregulated, and the association of Myc and Max with the promoter of the kinase was inhibited. In parallel, an increased association of Mad and Miz-1 was detected on DNA, associated with an inhibition of the recruitment of transcriptional coactivators. Interestingly, a gain of H3K9 trimethylation and HP1gamma recruitment was observed on the Aurora-A promoter following sn38 treatment, suggesting that this promoter is located within SAHF foci following genotoxic treatment. Since Aurora-A is involved in centrosome maturation, we observed as expected that topoisomerase I inhibition prevented centrosome separation but did not affect their duplication. As a consequence, this led to G2 arrest and senescence induction.These results suggest a model by which the Aurora-A gene is inactivated by the G2 checkpoint following topoisomerase I inhibition. We therefore propose the hypothesis that the coordinated overexpression of Myc and Aurora-A, together with a downregulation of Mad and Miz-1 should be tested as a prognosis signature of poor responses to topoisomerase I inhibitors.


The molecular basis of familial dysautonomia: overview, new discoveries and implications for directed therapies.
Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manifestations of FD have been extensively studied and therapeutic modalities have, until recently, focused primarily on addressing the symptoms experienced by those with this fatal disorder. The primary FD-causing mutation is an intronic nucleotide substitution that alters the splicing of the IKBKAP-derived transcript. Recent efforts have resulted in the development of new therapeutic modalities that facilitate the increased production of the correctly spliced transcript and mitigate the symptoms of those with FD. Furthermore, the recent demonstration of the reduced presence of monoamine oxidase A in cells and tissues of individuals with FD has provided new insight into the cause of hypertensive crises experienced by these patients.


Can facet joint fluid on MRI and dynamic instability be a predictor of improvement in back pain following lumbar fusion for degenerative spondylolisthesis?
To investigate the relationship between lumbar facet fluid and dynamic instability in degenerative spondylolisthesis (DS), as well as the relationship between facet fluid and patient-reported outcomes following a posterior lumbar fusion. We analyzed consecutive patients with degenerative spondylolisthesis undergoing single level posterior lumbar fusion from December 2010 to January 2013 at a single academic institution. We investigated the relationship between fluid in the facet joint as measured on axial MRI and the presence of dynamic instability. We investigated the impact of facet fluid, Modic changes, and dynamic instability on patient-reported outcomes. There was a significant association between the amount of facet joint fluid and the presence of dynamic instability (p = 0.03); as facet fluid increases, the probability of dynamic instability also increases. For every 1 mm of facet fluid, there was a 41.6 % increase (95 % CI 1.8-97) in the odds of dynamic instability. A facet fluid amount less than 0.5 mm gave a 90 % probability that there was no dynamic instability. The presence of facet fluid and dynamic instability were associated with achieving minimal clinical important difference (MCID) in low back pain following lumbar fusion (p = 0.04 and 0.05, respectively). Facet joint fluid is associated with the presence of dynamic instability in DS. The presence of facet fluid and dynamic instability may predict increased likelihood of achieving MCID for improvement in back pain following posterior lumbar fusion.


Silicone gel breast implant adverse event reports to the Food and Drug Administration, 1984-1995.
To characterize the adverse event reports on silicone gel breast implants (SGBIs), including death reports, submitted to the Food and Drug Administration (FDA) from 1984 through 1995 and to analyze changes in the type and complexity of reports following extensive media coverage of breast implants. The authors analyzed mandatory and voluntary reports from the adverse events reporting system for medical devices at the FDA. In 1988, adverse event reports related to SGBIs accounted for 2.4% of the 14,473 mandatory reports entered into the FDA database on medical devices. In 1992, SGBI-related reports accounted for 30.3% of the total 66,476 mandatory reports of adverse events. The most frequently reported adverse event in 1988, before the widespread publicity on breast implants, was implant burst or rupture. In contrast, in 1992 the most frequently reported event was reaction, a term used to describe a range of adverse effects. The numbers of mandatory and voluntary reports of SGBI-related adverse events increased exponentially, as did the complexity of the reports, following publicity over the lack of safety data on breast implants and a short voluntary moratorium on their sale. A significant proportion of reports lacked information on specific medical symptoms or diagnoses.


Heterogeneous expressions of hepcidin isoforms in hepatoma-derived cells detected using simultaneous LC-MS/MS.
Hepcidin, a key regulator of iron homeostasis, is known to have three isoforms: hepcidin-20, -22, and -25. Hepcidin-25 is thought to be the major isoform and the only one known to be involved in iron metabolism; the physiological roles of other isoforms are poorly understood. Because of its involvement in the pathophysiology of hereditary hemochromatosis and the anemia of chronic disease, the regulatory mechanisms of hepcidin expression have been extensively investigated, but most studies have been performed only at the transcriptional level. Difficulty in detecting hepcidin has impeded in vitro research. In the present study, we developed a novel method for simultaneous quantification of hepcidin-20, -22, and -25 in the media from hepatoma-derived cell lines. Using this method, we determined the expression patterns of hepcidin isoforms and the patterns of responses to various stimuli in human hepatoma-derived cultured cells. We found substantial differences among cell lines. In conclusion, a novel method for simultaneous quantification of hepcidin isoforms is presented. Heterogeneous expressions of hepcidin isoforms in human hepatoma-derived cells were revealed by this method. We believe our method will facilitate quantitative investigation of the role hepcidin plays in iron homeostasis.


Identifying predators - a role for veterinary pathologists (abstract).
Predator identification has traditionally been the domain of ecologists who have relied on the feeding sign left by various predator species at the nest or carcass. Thus destructive animals such as cats and dogs can be distinguished from relatively clean predators such as mustelids and messy predators such as possums and rats. The presence of scats or foot imprints, and the location of the nest or carcass are also useful signs, however in many cases it may be impossible to distinguish between predators and scavengers. New technology such as time-lapse photography and video surveillance are valuable tools but still cannot monitor every event. Veterinary pathology can play a useful role by carefully examining and recording the site and severity of lesions and distinguishing between ante- and post mortem tissue damage, using histopathology if necessary. Distances between the canine teeth can be measured from bite marks in the skin and subcutaneous tissues, and mammalian fur on the claws and beak of larger birds can be identified by measuring fibre length and diameter.


Do blood concentrates influence inflammatory signs and symptoms after mandibular third molar surgery? A systematic review and network meta-analysis of randomized clinical trials.
To investigate, through a network meta-analysis, the effectiveness of blood concentrates in reducing pain perception, trismus, and edema after mandibular third molar extraction. An electronic search was performed in nine databases to locate randomized clinical trials comparing blood concentrate use after mandibular third molar extraction. Two authors selected and extracted the data independently. The individual risk of bias in the studies was assessed with the RoB v2.0 tool. A network meta-analysis compared postoperative pain and trismus scores after applying different blood concentrates, using the mean difference (MD) as an effect estimate. The GRADE approach assessed the certainty of evidence. Thirty-one randomized clinical trials were included in the review and 18 in the meta-analysis. Leukocyte- and platelet-rich fibrin (L-PRF) was the most used blood concentrate, followed by platelet-rich plasma (PRP). The network meta-analysis, depending on the analyzed period, evaluated up to 1240 surgeries. Among the analyzed blood concentrates, advanced platelet-rich fibrin (A-PRF) performed better among the analyzed blood concentrates, decreasing postoperative pain in 1, 2, 3, and 7 days and reducing trismus up to the inflammatory peak compared to blood clots. Only two studies had a low risk of bias. Based on very low certainty of evidence, using concentrates seemed efficient compared to blood clots in reducing pain and trismus after mandibular third molar surgeries. A-PRF decreased postoperative pain throughout the evaluated time and trismus during the acute inflammatory peak. A-PRF after mandibular third molar extractions performed better among the analyzed blood concentrates and seemed efficient in improving postoperative quality by decreasing inflammatory signs and symptoms.


Effect of rehabilitation and botulinum toxin injection on gait in chronic stroke patients: a randomized controlled study.
Botulinum toxin injections are used to treat spasticity in stroke. Although this treatment is effective on muscle tone, its effect on functional gait-related activities remains uncertain. The aim of this randomized controlled trial was to determine the effect of a self-rehabilitation programme as an adjunct to botulinum toxin injections on gait-related activities in patients with chronic hemiparesis. Thirty-five outpatients were included. Each patient was randomized to 1 of 2 groups: botulinum toxin + standardized self-rehabilitation programme (R group, n = 19) or botulinum toxin alone (C group, n = 16). Each patient was evaluated with the following tests before botulinum toxin injections and one month afterwards: 10-m timed walk, Timed Up and Go, distance covered in 6 min over an ecological circuit, and the stair test. There were significant improvements in the R group compared with the C group: maximal gait speed improved by 8% (p = 0.003); distance covered in 6 min over an ecological circuit increased by 7.1% (p = 0.01); and time to ascend and to descend a flight of stairs decreased by 9.8% (p = 0.003) and 6.6% (p = 0.009), respectively. The self-rehabilitation programme was well tolerated and safe. These results strongly suggest that a standardized self-rehabilitation programme constitutes a useful adjunct to botulinum toxin injections in order to improve gait-related activities.


The potential of robotic technology applied to meet requirements for tools to support microsurgery and cellular surgery.
Microsurgery and processes involving cell manipulation or cell surgery are clinical practices where the operator works at or beyond the threshold of human dexterity. Current tools available are conventional in their design, and this limits consistency and the level of reliability and achievement. Surgical robotic devices have been explored to improve precision in minimal access surgical procedures to augment control of tool points in tissues, and have enabled feedback of sensory data from which the operator is able to deduce information on the tool at the working site. In this paper, relevant technologies are described that can be harnessed to improve perception of tool point interaction with tissues at the working site and to improve tool control at the small scale required in clinical practice for microsurgery and for cell surgery.


Theoretical design of durable and strong polycarbonates against photodegradation.
The photodegradation mechanism of polycarbonate (PC) was investigated by quantum chemistry, and a novel antidegradation molecular design using substituents was proposed. It was demonstrated that electron-withdrawing substituents in the phenyl moiety controlled bond alternation, leading to inhibition of the O-C bond cleavage in the carbonate moiety. These results provide a promising alternative for durable PC synthesis.


Open and Percutaneous Trigeminal Nucleotractotomy: A Case Series and Literature Review.
Nucleotractotomy is an efficient surgical technique that provides a high pain relief rate for specific clinical indications. There are two main approaches for performing this operation: an open and percutaneous technique. In the Federal Center of Neurosurgery (Novosibirsk, Russia) from 2016 to 2022, 13 trigeminal nucleotractotomies (7 open and 6 percutaneous) were performed in 12 patients (5 women and 7 men). The indications for surgery were deafferentation pain and chronic drug-resistant pain syndrome caused by malignancy in the facial region. A neurological examination was done on each patient 1 day before the surgery, right after the surgery, and at the follow-up (examinations were done after 1, 6, and 12 months, or when the patient independently applied to our hospital). In the early postoperative period, patients underwent brain MRI. The average pain intensity score before nucleotractotomy on the 11-point (0-10) visual analog scale (VAS) was 9.3. The effectiveness of open interventions was somewhat higher; the average VAS score in the early postoperative period for the open technique was 1.57, in the group of patients who underwent percutaneous nucleotractotomy were 2.66. Complete regression of the pain syndrome was achieved in 6 patients; in 5 patients, the pain in the face decreased by more than 50%. One case had an unsatisfactory outcome. In the open-surgery group in the early postoperative period, according to MRI, the average length of the visualized area of signal change was longer (21.5 mm, the average diameter was 3.75 mm) than in a percutaneous nucleotractotomy group (16 mm, the average diameter was 3.75 mm). During the postoperative period (average follow-up 40 months), the pain recurred in 3 patients (30%): 2 patients after percutaneous nucleotractotomy (3 and 18 months after surgery) and in 1 patient 4 months after the open surgery. The mean VAS score at the last follow-up was 2.6. Trigeminal nucleotractotomy is an effective approach to the treatment of intractable facial pain. Our experience suggests this technique is highly effective in patients with drug-resistant pain caused by craniofacial tumors and deafferentation conditions after treating trigeminal neuralgia.


In the Netherlands, approximately 200 to 300 patients are diagnosed with imported malaria every year. The symptoms of malaria are non-specific. The current gold standard for malaria diagnostics is to conduct a thick and thin blood smear. New diagnostic techniques are increasingly applied. At present, the treatment of uncomplicated malaria consists of an artemisinin-based combination therapy (ACT). An alternative treatment for malaria caused by P. vivax,P. knowlesi,P. ovale and P. malariae in the Netherlands is chloroquine. Severe malaria is treated with artesunate intravenously, followed by a full three-day course of oral ACT. Uncomplicated malaria during pregnancy is treated with an ACT (e.g. artemether-lumefantrine) and severe malaria with artesunate intravenously, the latter followed by a full three-day course of oral ACT. There is currently no malaria vaccine available for travellers.


Advancements and critical steps for statistical analyses in blood pressure response to resistance training in hypertensive older women: a methodological approach.
Repeated measures analysis of covariance and three-way analysis of variance with repeated measures are common statistical methods. For a valid interpretation of blood pressure (BP) response to exercise, a variety of additional statistical methods must be implemented. Four additional statistical methods are presented: technical error of measurement (SEM), smallest real difference (SRD), magnitude-based inference and mixed effect modeling technique (MEM). The aim of this perspective article is to demonstrate how to apply already known statistical analyses regarding BP responsiveness in order to improve interpretation and achieve higher reliability for future studies in exercise science. A total of 27 hypertensive older women (aged 68.37 ± 5.55 years) participated in the present study. A whole-body resistance training (RT) program was performed on two nonconsecutive days per week for 10 weeks. BP was monitored during the 10-week RT intervention and after 15 weeks of detraining. First, individuals were classified as high and low responders, then statistical methods to analyze data included the use of SEM, SRD, magnitude-based inference and MEM. When magnitude-based inference was used to classify responsiveness, most participants displayed a trivial response. Decrements in SBP between 1 and 10 mmHg were not clinically meaningful but fell within the measurement error of the SBP measurements. Baseline SBP and time of training predicted post-SBP response. Changes over time and declines in SBP might not be a SRD and fell in the SEM. Moreover, SBP responsiveness was the result of inappropriate control of covariates such as period of training.


Unequal lives: a sociodemographic analysis of COVID-19 transmission and mortality in India.
Existing socio-economic inequalities shape, in very particular and measurable ways, the differential impact that a disease has on different sections of the same society. This is particularly true of COVID-19, which has rapidly exhausted the public health system in India, and magnified the gradient of vulnerability in an underserved populace. Using publicly available data, we have aimed to deconstruct this gradient into individual variables of inequality and quantify their impact on the transmission and mortality outcomes of COVID-19 in India. Sociodemographic analysis. We quantify doubling times and case fatality ratios for all districts in India, then correlate them to 20 variables of socio-economic vulnerability and demographic structure. Variables that exhibit persistent correlation are then analysed using multivariate beta regression models to validate their impact on COVID-19 outcomes in India. The transmission of COVID-19 in India is enhanced by the lack of access to indoor latrines, drainage facilities, electricity, and proximate sources of drinking water. Transmission is slowed by the presence of an elderly population. Fatality rates relate negatively to an area's medical infrastructure and the presence of a college-educated populace. An interactive matrix of social inequalities, cultural practices, and behavioural patterns determines the path of COVID-19 through a community. Specific variables exhibit patterns of persistent vulnerability; others indicate a resistance to infection and mortality. This body of evidence, when incorporated into policy design, may lead to localised, need-sensitive models of intervention, both for preventive measures and medical care.


New antidepressant drug candidate: Hypericum montbretti extract.
This study was designed to investigate possible antidepressant-like effects of the extract prepared from the flowers of Hypericum montbretti Spach. (Guttiferae, Clusiaceae). Phytochemical constituents of the methanolic extract were analysed by HPLC method. The main flavonoid component was detected as rutin, and another highly concentrated phenolic compound was quercitrin. Antidepressant activity of the extract was examined by tail suspension and modified forced swimming tests, whereas the motor coordination of the animals was tested by the Rota-Rod apparatus. Reboxetine at a dose of 20 mg kg⁻¹ was used as a reference drug. Dose-dependent antidepressant activity was observed in both tests following the administration of extract at 100 and 250 mg kg⁻¹ doses. To the best of our knowledge, this is the first study reporting the antidepressant activity of H. montbretti extract. Additionally, the results of this work support previous papers reporting the antidepressant activity of rutin.


Retrospective cohort study: Effect of age as a barrier to diagnosis of eosinophilic oesophagitis.
Prior work suggests eosinophilic oesophagitis (EoE) is rare in those aged over 65 years. However, elderly patients with EoE experience a substantial diagnostic delay from symptom onset to diagnosis. To assess if age predicted whether oesophageal biopsies were obtained in patients with EoE symptoms, what clinical features predict EoE in the elderly, and if EoE phenotype differs between elderly and non-elderly patients. We conducted a retrospective cohort study utilising the University of North Carolina (UNC) electronic medical record, EoE clinicopathologic database and UNC endoscopy software from July 2008 to April 2021. A sample of 193 elderly and non-elderly patients with dysphagia, chest pain and/or heartburn were assembled. Patients with EoE were newly diagnosed per contemporaneous guidelines. Patient demographics, clinical characteristics and procedural data were extracted. Summary statistics, bivariate and multivariate analyses were performed. Of 193 patients, we included 91 elderly (47%) and 102 non-elderly (53%). Age independently predicted the odds of biopsies (adjusted odds ratio (aOR): 0.44 elderly vs. non-elderly; 95% CI: 0.21-0.92). Endoscopic features of EoE, but not symptoms, were more common in elderly than non-EoE elderly patients. Elderly patients with EoE differed from non-elderly only by time to diagnosis (aOR per year of symptoms preceding diagnosis: 1.08, 95% CI: 1.04-1.11). Elderly patients with EoE have <50% the odds of oesophageal biopsies. There were no significant differences between elderly and non-elderly EoE patients, although endoscopic features helped discriminate the two groups. Our findings suggest that older age represents a barrier to EoE diagnosis.


Fathers who kill their children: an analysis of the literature.
Roughly half of filicidal acts are committed by fathers, though the majority of the literature focuses on maternal filicide. This paper reviews the existing literature on paternal filicide with the goal of identifying characteristics common among these fathers. Fathers who killed their children were, on average, in their mid thirties. The mean age of their victims was five. They may have multiple victims. Sons and daughters were killed in equal numbers. Reasons included death related to abuse, mental illness (including psychosis and depression), and revenge against a spouse. The method often involved wounding violence. Suicide following the act occurred frequently. After being tried for their crimes, filicidal fathers were more frequently incarcerated than hospitalized. Given the range of those capable of this act, mental health professionals must be alert to the possibility of filicide in a variety of fathers. Considering this risk, clinicians should inquire about thoughts of harming children, partners, and themselves.


Course and outcome in individuals with atypical anorexia nervosa: Findings from the Study of Refeeding to Optimize iNpatient Gains (StRONG).
We previously reported that participants with atypical anorexia nervosa (atypical AN) had higher historical and admission weights, greater eating disorder psychopathology, but similar rates of amenorrhea and weight suppression at baseline as compared to anorexia nervosa (AN); here, we compare 1-year outcomes. Weight, % median body mass index (%mBMI), Eating Disorder Examination Questionnaire (EDE-Q) scores, resumption of menses, and rehospitalizations were examined at 3, 6, and 12 months post-discharge. Analyses (N = 111) compared changes in %mBMI, weight suppression, and EDE-Q scores over time between atypical AN and AN. Among the participants (48 atypical AN, 63 AN), both groups gained weight but those with atypical AN had lower gains than those with AN in %mBMI (p = .02) and greater weight suppression (p = .002) over time. EDE-Q scores improved over time, independent of weight suppression, with no significant difference between atypical AN and AN. Groups did not differ by rates of resumption of menses (80% atypical AN, 76.9% AN) or rehospitalization (29.2% atypical AN, 37.9% AN). Greater weight suppression predicted longer time to restore menses and more days of rehospitalization. Individuals with atypical AN regained a smaller proportion of body mass and were more weight suppressed over time. Change in eating disorder cognitions, resumption of menses, and rehospitalization rates at 1-year follow-up did not differ between groups. There was no significant difference in weight suppression between groups for those who were psychologically improved at 12 months. Findings highlight limitations in our understanding of weight recovery in atypical AN. New metrics for recovery are urgently needed. Little is known about outcome in atypical anorexia nervosa (atypical AN). We examined recovery metrics in young people with atypical AN and anorexia nervosa (AN) 1 year after medical hospitalization. Individuals with atypical AN showed slower weight gain and remained further from their pre-illness weight. There were no differences in the rates of psychological recovery, resumption of menses, or rehospitalization. New metrics are needed to assess recovery in atypical AN.


Sequence organization in Dictyostelium: unique structure at the 5'-ends of protein coding genes.
We have compared the sequences which lie 5' to the coding regions of 15 Dictyostelium genes transcribed by RNA polymerase II. These sequences are extremely (approximately 90%) A + T rich and contain extensive homopolymeric regions. Like most eukaryotic genes, those in Dictyostelium possess a TATA or Goldberg-Hogness Box approximately 25-35bp 5' to the site of transcription initiation. In addition, each gene contains an oligo (dT) stretch between the TATA Box and mRNA start site; this oligo (dT) sequence is, thus far, unique to Dictyostelium. We suggest that the TATA-oligo (dT) structure is an essential component of the Dictyostelium promoter. The general sequence structure of coding, non-coding and untranscribed flanking regions in Dictyostelium is also discussed.


Delayed release of an abnormal fibrinopeptide A from fibrinogen Manchester: effect of the A alpha 16 Arg leads to His substitution upon fibrin monomer polymerization and the immunological crossreactivity of the peptide.
Fibrinogen Manchester is an abnormal fibrinogen with an impaired release of fibrinopeptide A (FPA) and a polymerization abnormality. In the accompanying article we have identified the amino acid substitution in fibrinogen Manchester as A alpha 16 Arg leads to His. When fibrinogen Manchester was digested with low thrombin concentrations approximately 40-50% of the total FPA content was release at a rate similar to FPA release from normal fibrinogen. The fibrin so formed exhibited an impaired polymerization of monomers. Digestion of fibrinogen Manchester with high concentrations of thrombin for prolonged times released the remaining FPA which had an abnormal retention time when studied by high performance liquid chromatography (HPLC). This fibrinopeptide has been shown previously to contain the A alpha 16 Arg leads to His substitution. fibrin resulting from this exhaustive digestion had normal polymerization of monomers. The normal and substituted FPAs were isolated by HPLC and compared in a double antibody competitive-binding assay for normal FPA. The immunological cross-reactivity of the abnormal peptide was reduced, so that approximately 5 times more abnormal peptide was required on a molar basis to displace labelled normal FPA. Normal intact fibrinogen was 10-fold less reactive (on a half molar basis) than free normal FPA and the crossreactivity of fibrinogen Manchester was measurably less than that of normal fibrinogen. It is concluded that immunological measurement alone of FPA released from abnormal fibrinogens may not give a complete description of the kinetics of peptide release if the amino acid substitution lies within the FPA sequence. The combination of radioimmunoassay and HPLC, however, provides a powerful analytical approach that should be useful in classifying and characterizing abnormal fibrinogens.


Acculturation and orofacial pain among Hispanic adults.
This study examined the associations between acculturation and orofacial pain and healthcare among Hispanic adults. Understanding the effects of acculturation on Hispanic oral health may improve understanding of oral health disparities in the United States. Data were collected from 911 Hispanic adults reporting tooth pain and painful oral sores who were part of a larger study of South Florida residents conducted using random-digit dialing methodology. The survey was conducted in Spanish or English by bilingual interviewers per the choice of each respondent. Greater use of the Spanish language was associated with disparities in healthcare visits for orofacial pain, not having a usual dentist, having greater pain, increased difficulty eating and sleeping, and more depression. Respondents' and their parents' nativity (families that had been in the United States longer) and those identifying more closely to Hispanic culture were also predictive of several of the outcomes. Gender, financial status, and age, independent of acculturation, were also associated with orofacial pain, accessing health care, and pain-related loss of functioning among Hispanics. The data support the hypothesis that Hispanics with less acculturation are less able to access needed oral health care. This study highlights the need for outreach programs targeting recent Hispanic immigrants focusing on oral health care. This study found that lower levels of acculturation, particularly less frequent use of English, were associated with greater oral pain and depression for Hispanics adults. This emphasizes the need to provide Hispanic patients with information in Spanish and the importance of having bilingual materials and staff in dental clinics.


Low-glutamine fed-batch cultures of 293-HEK serum-free suspension cells for adenovirus production.
Recent developments in gene therapy using adenoviral (Ad) vectors have fueled renewed interest in the 293 human embryonic kidney cell line traditionally used to produce these vectors. Low-glutamine fed-batch cultures of serum-free, suspension cells in a 5-L bioreactor were conducted. Our aim was to tighten the control on glutamine metabolism and hence reduce ammonia and lactate accumulation. Online direct measurement of glutamine was effected via a continuous cell-exclusion system that allows for aseptic, cell-free sampling of the culture broth. A feedback control algorithm was used to maintain the glutamine concentration at a level as low as 0.1 mM with a concentrated glucose-free feed medium. This was tested in two media: a commercial formulation (SFM II) and a chemically defined DMEM/F12 formulation. The fed-batch and batch cultures were started at the same glucose concentration, and it was not controlled at any point in the fed-batch cultures. In all cases, fed-batch cultures with double the cell density and extended viable culture time compared to the batch cultures were achieved. An infection study on the high density fed-batch culture using adenovirus-green fluorescent protein (Ad-GFP) construct was also done to ascertain the production capacity of the culture. Virus titers from the infected fed-batch culture showed that there is an approximately 10-fold improvement over a batch infection culture. The results have shown that the control of glutamine at low levels in cultures is sufficient to yield significant improvements in both cell densities and viral production. The applicability of this fed-batch system to cultures in different media and also infected cultures suggests its potential for application to generic mammalian cell cultures.


Gabapentin is a first line drug for the treatment of neuropathic pain in spinal cord injury.
Prospective, randomized, double blind, placebo-controlled, crossover clinical trial. To determine the efficacy of gabapentin in the treatment of neuropathic pain related to spinal cord injury. Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. Neuropathic pain associated with spinal cord injury is quite refractory, and current treatments are not effective. Gabapentin, an anticonvulsant, has become the first choice in the treatment of neuropathic pain. The place of gabapentin in the treatment of spinal cord injury-related neuropathic pain was questioned in only a few recent reports; however, they are retrospectively designed, nonstandardized, and uncontrolled studies, or involve a very small series of patients using less than optimum doses. A total of 18-week study period included a 4-week medication/placebo titration period. This was followed by a 4-week stable dosing period when the patients continued to receive maximum tolerated doses, a 2-week washout period, then a crossover of 4 weeks of medication/placebo titration, and another 4 weeks of stable dosing period. Twenty paraplegic patients (female/male: 7/13) with complete spinal cord injury at the thoracic and lumbar level, aged between 20 and 65 years, with neuropathic pain for more than 6 months were recruited for the study. All patients completed the study. Gabapentin reduced the intensity as well as the frequency of pain, relieved all neuropathic pain descriptors except the itchy, sensitive, dull, and cold types, and improved the quality of life (P < 0.05). Gabapentin can be added to the list of first-line medications for the treatment of chronic neuropathic pain in spinal cord injury patients. It is a promising new agent and offers advantages over currently available treatments.


Influence of tubule orientation on cone-shaped texture development in laser-ablated dentin.
In the present paper, the influence of tubule orientation on surface texture development was studied. Specimens of dentin with a wide range of tubule orientations were extracted from caries-free human teeth, processed using KrF laser radiation, and analyzed by scanning electron microscopy. When a transverse cross section of dentin cut perpendicularly to the tooth axis is processed with KrF laser radiation, a cone-like topography develops in the inner dentin where tubules are parallel to the laser beam. When laser processing is carried out in the outer dentin, because tubules are significantly tilted with respect to the laser beam, flat surfaces are achieved. The surface texture after laser processing depends effectively on the angle between the tubules and the laser beam. The dependency of cone growth on tubule orientation was confirmed using a simple differential ablation model.


Complex imaging features of accidental cerebral intraventricular gadolinium administration.
Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) is a contrast agent commonly used for enhancing MRI. In this paper, the authors report on 2 cases of postoperative inadvertent administration of Gd-DTPA directly into a ventriculostomy tubing side port that was mistaken for intravenous tubing. Both cases demonstrated a low signal on MRI throughout the ventricular system and dependent portions of the subarachnoid spaces, which was originally believed to be CSF with areas of T1 shortening in the nondependent portions of the subarachnoid spaces, and misinterpreted as basal leptomeningeal enhancement and meningitis. The authors propose that the appearance of profound T1 hypointensity within the ventricles and diffuse susceptibility artifact along the ependyma is pathognomonic of intraventricular Gd-DTPA and should be recognized.


State-of-the-art treatment of coccidioidomycosis: skin and soft-tissue infections.
Coccidioidomycosis is a fungal infection common in the southwestern United States that is caused by the endemic Coccidioides species of fungus. Coccidioidal infections are generally manifested as self-limited respiratory illnesses, but affected patients rarely present with coccidioidomycosis in extrapulmonary locations. Skin and soft-tissue coccidioidomycosis may occur in 15% to 67% of patients with disseminated infection. Skin manifestations of coccidioidomycosis can either be reactive rashes, such as erythema multiforme or erythema nodosum associated with primary pulmonary infection, or they can be the result of extrapulmonary dissemination of the infection to the skin. As many as 90% of persons with disseminated infection to the skin have other extrapulmonary sites of infection, and the presence of coccidioidal skin lesions should prompt an investigation for other extrapulmonary foci of infection. Lymph nodes are a common site of extrapulmonary infection. Nearly every organ system and soft-tissue have been described as infected with Coccididioides species, but subcutaneous abscesses, phlegmon, and sinus tracts are not uncommon and often are themselves the result of coccidioidal infection in neighboring lymph nodes, bones, or joints. A biopsy of the abnormal area is the most direct way to diagnose skin and soft-tissue lesions. Fluconazole and itraconazole are preferred therapeutic agents, and surgical intervention may be required as an adjunctive measure. This article reviews the types and locations of disseminated infections, as well as diagnostic studies and treatment of this difficult-to-treat manifestation of coccidioidomycosis.


End modification of a linear DNA duplex enhances NER-mediated excision of an internal Pt(II)-lesion.
The study of DNA repair has been facilitated by the development of extract-based in vitro assay systems and the use of synthetic DNA duplexes that contain site-specific lesions as repair substrates. Unfortunately, exposed DNA termini can be a liability when working in crude cell extracts because they are targets for DNA end-modifying enzymes and binding sites for proteins that recognize DNA termini. In particular, the double-strand break repair protein Ku is an abundant DNA end-binding protein that has been shown to interfere with nucleotide excision repair (NER) in vitro. To facilitate the investigation of NER in whole-cell extracts, we explored ways of modifying the exposed ends of synthetic repair substrates to prevent Ku binding and improve in vitro NER efficiency. Replacement of six contiguous phosphodiester linkages at the 3'-ends of the duplex repair substrate with nuclease-resistant nonionic methylphosphonate linkages resulted in a 280-fold decrease in binding affinity between Ku and the modified duplex. These results are consistent with the published crystal structure of a Ku/DNA complex [Walker et al. (2001) Nature 412, 607-614] and show that the 3'-terminal phosphodiester linkages of linear DNA duplexes are important determinants in DNA end-binding by Ku. Using HeLa whole-cell extracts and a 149-base pair DNA duplex repair substrate, we tested the effects of modification of exposed DNA termini on NER-mediated in vitro excision of a 1,3-GTG-Pt(II) intrastrand cross-link. Methylphosphonate modification at the 3'-ends of the repair substrate resulted in a 1.6-fold increase in excision. Derivatization of the 5'-ends of the duplex with biotin and subsequent conjugation with streptavidin to block Ku binding resulted in a 2.3-fold increase excision. By combining these modifications, we were able to effectively reduce Ku-derived interference of NER excision in vitro and observed a 4.4-fold increase in platinum lesion excision. These modifications are easy to incorporate into synthetic oligonucleotides and may find general utility whenever synthetic linear duplex DNAs are used as substrates to investigate DNA repair in whole-cell extracts.


Transformation of mouse C3H/10T1/2 cells by single and fractionated doses of X-rays and fission-spectrum neutrons.
A mouse embryo-derived cell line, C3H/10T1/2, was used to measure the frequency of in vitro neoplastic transformation induced by 50-kVp X-rays and by fission-spectrum neutrons from the JANUS reactor at the Argonne National Laboratory. The transformation frequency after single X-ray doses rises exponentially, reaching a plateau at about 3 X 10(-3) transformant/survivor. The induction curve following single neutron doses, while qualitatively similar, initially rises more steeply and levels off at a maximum of about 6 X 10(-3) transformant/survivor. For both radiations, transformation frequency varies with changes in the number of viable cells per dish, showing about a 10-fold decrease in transformation frequency when the number of viable cells per 90-mm dish was increased from about 300 to about 1000. Fractionation of a total X-ray dose of 700 rads results in an approximately 6-fold increase in survival and reduction in transformation frequency over a 16-hr interval. Fractionation of the total neutron dose of 378 rads has no effect upon cell survival, and transformation frequency declines by a factor of only about 1.7 at most over a 24-hr period. Cells derived from transformed foci formed fibrosarcomas when injected into appropriately treated mice.


Influences of Culture and Visual Context on Real-Time Social Categorization.
Social categorization is often thought to be based on facial features and immune to visual context. Moreover, East Asians have been argued to attend to context more than Westerners. American and Chinese participants were presented with faces varying along a White-Asian morph continuum either in American, neutral, or Chinese contexts. American contexts made White categorizations more likely, and Chinese contexts made Asian categorizations more likely. Further, the compatibility between facial and contextual cues influenced the directness of participants' hand trajectories en route to selecting a category response. Even when an ultimate response was not biased by context, the trajectory was nevertheless partially attracted to the category response associated with the context. Importantly, such partial attraction effects in hand trajectories revealed that the influence of context began earlier in time for Chinese relative to American participants. Together, the results show that context systematically influences social categorization, sometimes altering categorization responses and other times only temporarily altering the process. Further, the timing of contextual influences differs by culture. The findings highlight the role of contextual and cultural factors in social categorization.


Impact of junior doctor strikes on patient flow in the emergency department: a cross-sectional analysis.
Healthcare worker strikes are a global phenomenon. Mortality and morbidity seem to be unaffected by doctor strikes, but there is little evidence on the impact on emergency department (ED) flow and patient characteristics. In March and April 2023, two consecutive UK junior doctor strikes occurred. This study investigated the impact of junior doctor strikes on ED patient flow. Additionally, variation in patient presentations was compared between non-strike and strike days. This cross-sectional study was conducted at King's College Hospital ED, a university hospital in London. All ED attendances during the 72- and 96-hour strike actions were compared with the corresponding non-strike days of the previous week. National key performance indicators (KPIs) were analysed and compared between non-strike and strike days. Patients' demographics, acuity and diagnoses were compared. Outcome measures included number of 4-hour breaches, number of patients admitted or discharged and ED mortality. Staff seniority was categorised into levels for analysis. There was increased ED patient flow during strike days with a significantly shorter total time in department in March [240 min (IQR 155-469) vs. 286 min (IQR 198.5-523.5), P < 0.001] and in April [222.5 min (IQR 147-351) vs. 251.5 min (IQR 174-443), P < 0.001]. Time to first clinician, treatment, and decision to admit were all shorter during both strike actions. Number of attendances, acuity, diagnoses, admission, discharge, and mortality rates were similar during strike and non-strike days. Staffing numbers were lower or equivalent on strike days but level of seniority was higher (P < 0.001). The improved KPIs and increased patient flow during strike days, while multifactorial, seem largely attributed to the higher number of senior staff. Patient presentations and outcomes were unaffected by junior doctor strike action.


Mechanocellular models of epithelial morphogenesis.
Embryonic epithelia achieve complex morphogenetic movements, including in-plane reshaping, bending and folding, through the coordinated action and rearrangement of individual cells. Technical advances in molecular and live-imaging studies of epithelial dynamics provide a very real opportunity to understand how cell-level processes facilitate these large-scale tissue rearrangements. However, the large datasets that we are now able to generate require careful interpretation. In combination with experimental approaches, computational modelling allows us to challenge and refine our current understanding of epithelial morphogenesis and to explore experimentally intractable questions. To this end, a variety of cell-based modelling approaches have been developed to describe cell-cell mechanical interactions, ranging from vertex and 'finite-element' models that approximate each cell geometrically by a polygon representing the cell's membrane, to immersed boundary and subcellular element models that allow for more arbitrary cell shapes. Here, we review how these models have been used to provide insights into epithelial morphogenesis and describe how such models could help future efforts to decipher the forces and mechanical and biochemical feedbacks that guide cell and tissue-level behaviour. In addition, we discuss current challenges associated with using computational models of morphogenetic processes in a quantitative and predictive way.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.


Conductance quantisation in patterned gate In0.75Ga0.25As structures up to 6 × (2e 2/h).
We present electrical measurements from In0.75Ga0.25As 1D channel devices with Rashba-type, spin-orbit coupling present in the 2D contact regions. Suppressed backscattering as a result of the time-reversal asymmetry at the 1D channel entrance results in enhanced ballistic transport characteristics with clear quantised conductance plateaus up to 6 × (2e 2/h). Applying DC voltages between the source and drain ohmic contacts and an in-plane magnetic field confirms a ballistic transport picture. For asymmetric patterned gate biasing, a lateral spin-orbit coupling effect is weak. However, the Rashba-type spin-orbit coupling leads to a g-factor in the 1D channel that is reduced in magnitude from the 2D value of 9 to ~6.5 in the lowest subband when the effective Rashba field and the applied magnetic field are perpendicular.


Twitching motility among pathogenic Xylella fastidiosa isolates and the influence of bovine serum albumin on twitching-dependent colony fringe morphology.
Fourteen Xylella fastidiosa isolates from grapevines exhibiting Pierce's disease symptoms in California, Texas, and South Carolina were examined for type IV pilus-mediated twitching motility, a phenotype previously observed in a Temecula isolate from California. All isolates except one from South Carolina (SC 19A97) exhibited colonies with a peripheral fringe on PW agar, a feature indicative of twitching motility; however, when individual cells of SC 19A97 were examined at higher magnifications twitching motility was observed. The presence and width of colony peripheral fringes were related to the amount of bovine serum albumin (BSA) present in the medium; no or low levels of BSA (0-1.8 g L(-1)) permitted development of the widest fringe, whereas higher levels (3.5-6.0 g L(-1)) severely limited, and in many instances prevented, peripheral fringe development. The growth rate of the wild-type Temecula isolate in PW broth with different concentrations of BSA was similar for all tested concentrations of BSA; however, growth was significantly reduced in medium without BSA.


Cadaveric feasibility study of da Vinci Si-assisted cochlear implant with augmented visual navigation for otologic surgery.
To our knowledge, this is the first reported cadaveric feasibility study of a master-slave-assisted cochlear implant procedure in the otolaryngology-head and neck surgery field using the da Vinci Si system (da Vinci Surgical System; Intuitive Surgical, Inc). We describe the surgical workflow adaptations using a minimally invasive system and image guidance integrating intraoperative cone beam computed tomography through augmented reality. To test the feasibility of da Vinci Si-assisted cochlear implant surgery with augmented reality, with visualization of critical structures and facilitation with precise cochleostomy for electrode insertion. Cadaveric case study of bilateral cochlear implant approaches conducted at Intuitive Surgical Inc, Sunnyvale, California. Bilateral cadaveric mastoidectomies, posterior tympanostomies, and cochleostomies were performed using the da Vinci Si system on a single adult human donor cadaveric specimen. Radiographic confirmation of successful cochleostomies, placement of a phantom cochlear implant wire, and visual confirmation of critical anatomic structures (facial nerve, cochlea, and round window) in augmented stereoendoscopy. With a surgical mean time of 160 minutes per side, complete bilateral cochlear implant procedures were successfully performed with no violation of critical structures, notably the facial nerve, chorda tympani, sigmoid sinus, dura, or ossicles. Augmented reality image overlay of the facial nerve, round window position, and basal turn of the cochlea was precise. Postoperative cone beam computed tomography scans confirmed successful placement of the phantom implant electrode array into the basal turn of the cochlea. To our knowledge, this is the first study in the otolaryngology-head and neck surgery literature examining the use of master-slave-assisted cochleostomy with augmented reality for cochlear implants using the da Vinci Si system. The described system for cochleostomy has the potential to improve the surgeon's confidence, as well as surgical safety, efficiency, and precision by filtering tremor. The integration of augmented reality may be valuable for surgeons dealing with complex cases of congenital anatomic abnormality, for revision cochlear implant with distorted anatomy and poorly pneumatized mastoids, and as a method of interactive teaching. Further research into the cost-benefit ratio of da Vinci Si-assisted otologic surgery, as well as refinements of the proposed workflow, are required before considering clinical studies.


The Relative Performance of Ensemble Methods with Deep Convolutional Neural Networks for Image Classification.
Artificial neural networks have been successfully applied to a variety of machine learning tasks, including image recognition, semantic segmentation, and machine translation. However, few studies fully investigated ensembles of artificial neural networks. In this work, we investigated multiple widely used ensemble methods, including unweighted averaging, majority voting, the Bayes Optimal Classifier, and the (discrete) Super Learner, for image recognition tasks, with deep neural networks as candidate algorithms. We designed several experiments, with the candidate algorithms being the same network structure with different model checkpoints within a single training process, networks with same structure but trained multiple times stochastically, and networks with different structure. In addition, we further studied the over-confidence phenomenon of the neural networks, as well as its impact on the ensemble methods. Across all of our experiments, the Super Learner achieved best performance among all the ensemble methods in this study.


Case Study: Improving the Quality of Dairy Cow Reconstruction with a Deep Learning-Based Framework.
Three-dimensional point cloud generation systems from scanning data of a moving camera provide extra information about an object in addition to color. They give access to various prospective study fields for researchers. With applications in animal husbandry, we can analyze the characteristics of the body parts of a dairy cow to improve its fertility and milk production efficiency. However, in the depth image generation from stereo data, previous solutions using traditional stereo matching algorithms have several drawbacks, such as poor-quality depth images and missing information in overexposed regions. Additionally, the use of one camera to reconstruct a comprehensive 3D point cloud of the dairy cow has several challenges. One of these issues is point cloud misalignment when combining two adjacent point clouds with the small overlapping area between them. In addition, another drawback is the difficulty of point cloud generation from objects which have little motion. Therefore, we proposed an integrated system using two cameras to overcome the above disadvantages. Specifically, our framework includes two main parts: data recording part applies state-of-the-art convolutional neural networks to improve the depth image quality, and dairy cow 3D reconstruction part utilizes the simultaneous localization and calibration framework in order to reduce drift and provide a better-quality reconstruction. The experimental results showed that our approach improved the quality of the generated point cloud to some extent. This work provides the input data for dairy cow characteristics analysis with a deep learning approach.


Operationalizing the Deployment of Low-Titer O-Positive Whole Blood Within a Regional Trauma System.
The implementation of a low-titer O+ whole blood (LTOWB) resuscitation algorithm, particularly in the prehospital environment, has several inherent challenges, including cost, limited and inconsistent supply, and the logistics of cold-chain management. The Southwest Texas Regional Advisory Council has implemented the nation's first multidisciplinary, multi-institutional regional LTOWB program. This research effort was to illustrate the successful deployment of LTOWB within a regional trauma system. A deliberate systems approach to the deployment of LTOWB was used. Tenets of this program included the active management of blood donor sources and blood supply levels to minimize wastage as a result of expiration, maximize product utilization, the use of prehospital transfusion triggers, and efforts to decrease program costs prehospital agencies. A novel LTOWB rotation system was established using the concept of a "rotation site" and "rotation center." Standardized transfusion criteria, a regional approved equipment list, a regional Prehospital Blood Product Transfusion Record, and a robust multilevel communication plan serves as the framework for the program. The San Antonio Whole Blood Consortium was developed to create a consensus driven forum to manage and guide the program. From January 2018 to October 2019, LTOWB has been placed at 18 helicopter emergency medical services (HEMS) bases, 12 ground emergency medical service (EMS) agencies, 1 level I trauma center, and 1 level IV trauma center. A total of 450 patients have received a prehospital LTOWB transfusion. Program wide, the wastage rate of LTOWB due to expiration is between 1% and 2%. No complications related to prehospital LTOWB administration have been identified. This work demonstrates a novel model for the development of a trauma system LTOWB program. The program's implementation augments remote damage control resuscitation strategies and requires the integration and collaboration of a multidisciplinary stakeholder team to optimize efficiency, performance, and safety of the program.


Association of Hospital Volume With Laryngectomy Outcomes in Patients With Larynx Cancer.
A volume-outcome association exists for larynx cancer surgery, but to date it has not been investigated for specific surgical procedures. To characterize the volume-outcome association specifically for laryngectomy surgery and to identify a minimum hospital volume threshold associated with improved outcomes. In this cross-sectional study, the Nationwide Inpatient Sample was used to identify 45 156 patients who underwent laryngectomy procedures for a malignant laryngeal or hypopharyngeal neoplasm between January 2001 and December 2011. The analysis was performed in 2018. Hospital laryngectomy volume was modeled as a categorical variable. Associations between hospital volume and in-hospital mortality, complications, length of hospitalization, and costs were examined using multivariate logistic regression analysis. Among 45 156 patients (mean age, 62.6 years; age range, 20-96 years; 80.2% male) at 5516 hospitals, higher-volume hospitals were more likely to be teaching hospitals in urban locations; were more likely to treat patients who had hypopharyngeal cancer, were of white race/ethnicity, were admitted electively, had no comorbidity, and had private insurance; and were more likely to perform flap reconstruction or concurrent neck dissection. After controlling for all other variables, hospitals treating more than 6 cases per year were associated with lower odds of surgical and medical complications, with a greater reduction in the odds of complications with increasing hospital volume. High-volume hospitals in the top-volume quintile (>28 cases per year) were associated with decreased odds of in-hospital mortality (odds ratio, 0.45; 95% CI, 0.23-0.88), postoperative surgical complications (odds ratio, 0.63; 95% CI, 0.50-0.79), and acute medical complications (odds ratio, 0.63; 95% CI, 0.48-0.81). A statistically meaningful negative association was observed between very high-volume hospital care and the mean incremental length of hospitalization (-3.7 days; 95% CI, -4.9 to -2.4 days) and hospital-related costs (-$4777; 95% CI, -$9463 to -$900). Laryngectomy outcomes appear to be associated with hospital volume, with reduced morbidity associated with a minimum hospital volume threshold and with reduced mortality, morbidity, length of hospitalization, and costs associated with higher hospital volume. These data support the concept of centralization of complex care at centers able to meet minimum volume thresholds to improve patient outcomes.


Measurement of second-order coherence in a light beam using a microscope and a grating.
The measurement of the complex cross-spectral density function of a light beam is discussed using a new type of shearing interferometer. This interferometer is composed principally of only an imaging lens system such as a microscope and an ordinary transparent diffraction grating replica. This interferometer is selfaligning, inexpensive, and able to introduce precise wavefront shears of the order of a few light wavelengths. A theoretical analysis of the instrument is developed giving expressions for calculating the magnitude and phase of the cross-spectral density function using observable properties of the interference pattern formed by the instrument. A simple experiment is described which demonstrates the operation of the instrument.


Sleep and cognitive functioning in childhood: Ethnicity, socioeconomic status, and sex as moderators.
We examined children's sleep at age 9 as a predictor of developmental trajectories of cognitive performance from ages 9 to 11 years. The effects of sleep on cognition are not uniform and thus we tested race/ethnicity, socioeconomic status (SES), and sex as moderators of these associations. At the first assessment, 282 children aged 9.44 years (52% boys, 65% European American [EA], 35% African American [AA]) participated. Two more waves of data collection spaced 1 year apart followed. The majority of children (63%) were living at or below the poverty line. Children's sleep was measured objectively with actigraphy and 2 well-established sleep parameters were derived: duration, indexed by sleep minutes between sleep onset and wake time, and quality, indexed by efficiency. Multiple cognitive functioning domains were examined with the Woodcock Johnson Tests of Cognitive Abilities (WJ III). Across the sample, higher sleep efficiency, but not duration, was associated with better cognitive performance. Significant moderation effects emerged. Controlling for SES, AA children scored lower on general intellectual ability and working memory (WM) at age 11 only if they experienced lower sleep efficiency at age 9. Further, boys scored lower on general abilities and processing speed (PS) at age 11 only if their sleep efficiency was lower at age 9. Findings indicate that lower sleep efficiency may contribute to lower cognitive functioning especially for AA children and boys. These vulnerabilities appear to emerge early in development and are maintained over time. Results underscore the importance of individual differences in explicating relations between sleep and children's cognitive performance. (PsycINFO Database Record


Quantitative structure-biotransformation relationships of organic micropollutants in aerobic and anaerobic wastewater treatments.
Biotransformation is one of the dominant processes to remove organic micropollutants (OMPs) in wastewater treatment. However, studies on the role of molecular structure in determining the biotransformation rates of OMPs are limited. We evaluated the biotransformation of 14 OMPs belonging to different chemical classes under aerobic and anaerobic conditions, and then explored the quantitative structure-biotransformation relationships (QSBRs) of the OMPs based on biotransformation rates using valid molecular structure descriptors (electrical and physicochemical parameters). Pseudo-first-order kinetic modeling was used to fit the biotransformation rate, and only 3 of the 14 OMPs showed that the biotransformation rate constant (kbio) values were higher under anaerobic conditions than aerobic conditions, indicating that aerobic conditions were more favorable for biotransformation of most OMPs. QSBRs infer that the electrophilicity index (ω) is a reliable predictor for OMPs biotransformation under aerobic conditions. ω corresponds to the interaction between OMPs and microbial enzyme active sites, this process is the rate-limiting step of biotransformation. However, under anaerobic conditions the QSBR based on ω was not significant, indicating that specific functional groups may be more critical than electrophilicity. In conclusion, QSBRs can serve as alternative tools for the prediction of the biotransformation of OMPs and provide further insights into the factors that influence biotransformation.


Peritoneal Dialysis for the Treatment of Cardiorenal Syndrome Type 1: A Prospective Brazilian Study.
This study aimed to explore the role of high-volume peritoneal dialysis (HVPD) in cardiorenal syndrome (CRS) type 1 patients in relation to metabolic and fluid control and outcome. Sixty-four patients were treated by HVPD (prescribed Kt/V = 0.50/session), flexible catheter and cycler. Mean age was 68.8 ± 15.4 years, 54.7% needed intravenous inotropic agents and/or intravenous vasodilators, 31.2% were on mechanical ventilation, acute coronary syndrome (ACS) was the main cause of acute disease heart failure (ADHF) 48.3%, median left ventricular ejection fraction (LVEF) was 38% and the main dialysis indications were uremia and hypervolemia. Blood ureic nitrogen and creatinine levels stabilized after 4 sessions at around 50 and 4 mg/dL, respectively. Negative fluid balance (FB) and ultrafiltration (UF) increased progressively and stabilized around 2.6 L and -2.5 L/day, respectively. Weekly-delivered Kt/V was 3.0 ± 0.42, and 32.8% died. There was a significant difference between the survivors (S) and non-survivors (NS) in age (71.4 ± 15.7 vs 63.6 ± 17.6, p < 0.001), main diagnosis of ADHF (ACS: 76.2 vs 34.8%, p = 0.04), mechanical ventilation (52.4 vs 20.1%, p = 0.03), fluid overload (FO) at predialysis moment (52.4 vs 25.6%, p = 0.04), and FB and UF from the 2nd to 5th dialysis session. In conclusion, HVPD treatment was effective in CRS type 1 patients, allowing adequate metabolic and fluid control. Age, ACS, FO and positive FB after 2 HVPD sessions were higher in NS patients.


An iminodibenzyl-quinoxaline-iminodibenzyl scaffold as a mechanochromic and dual emitter: donor and bridge effects on optical properties.
The influence of phenyl linkage and donor strength on the photophysical properties of new derivatives of quinoxaline-containing iminodibenzyl and iminostilbene moieties is studied. The donor-acceptor derivatives showed dual thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) despite a large energy gap between the excited singlet and triplet states (ca. 0.5 eV). This extremely rare observation is explained by the twisted and rigidified structure of the iminodibenzyl moiety.


Roles of fibroblast growth factor-inducible 14 in hepatocellular carcinoma.
The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressions in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson χ(2) test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.


Role of antibodies to self-antigens in chronic allograft rejection: potential mechanism and therapeutic implications.
Significant progress has been made in preventing acute allograft rejection following solid organ transplantation resulting in improved allograft survival. However, long term function still remains disappointing primarily due to chronic allograft rejection. Alloimmune responses primarily defined by the development of antibodies (Abs) to donor mismatched major histocompatibility antigens during the post-transplantation period have been strongly correlated to the development of chronic rejection. In addition, recent studies have demonstrated an important role for autoimmunity including the development of Abs to organ specific self-antigens in the pathogenesis of chronic allograft rejection. Based on this, a new paradigm has evolved indicating a possible cross-talk between the alloimmune responses and autoimmunity leading to chronic rejection. In this review, we will discuss the emerging concept for the role of cellular and humoral immune responses to self-antigens in the immunopathogenesis of chronic allograft rejection which has the potential to develop new strategies for the prevention and/or treatment of chronic rejection.


Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli.
Rat monoclonal antibody FA/11 has been used to identify macrosialin, a sialoglycoprotein confined to murine mononuclear phagocytes and related cells. Originally identified as a macrophage-associated glycoprotein predominantly localized in intracellular membranes (Smith, M.J., and G.L.E. Koch. 1987. J. Cell Sci. 87:113), the antigen is widely expressed on tissue macrophages, including those in lymphoid areas, and is expressed at low levels on isolated dendritic cells. Immuno-adsorption experiments reported here show that macrosialin is identical to the major 87-115-kD sialoglycoprotein previously identified by lectin blotting in exudate but not resident peritoneal macrophages (Rabinowitz, S., and S. Gordon. 1989. J. Cell Sci. 93:623). Resident peritoneal macrophages express low levels of macrosialin antigen in a glycoform that does not bind 125I wheat germ agglutinin or 125I peanut agglutinin; inflammatory stimuli upregulate expression of this antigen (up to 17-fold), in an alternative glycoform that is detected by these lectins. Pulse-chase experiments reveal a 44-kD core peptide that initially bears high-mannose chains (giving Mr 66 kD) and is subsequently processed to a mature protein of Mr 87-104 kD. Each glycoform contains N-linked glycan, as well as O-linked sugar structures that show alternative processing. Poly-N-acetyllactosamine structures are detected in the exudate cell glycoform only. This new marker for mononuclear phagocytes illustrates two strategies by which macrophages remodel their membranes in response to inflammatory stimuli. Its predominantly intracellular location and restricted cell distribution suggest a possible role in membrane fusion or antigen processing.


A comparison of the effects of progesterone sponges and ear implants, PGF2alpha, and their combination on efficacy of estrus synchronization and fertility of Mashona goat does.
Efficacy of estrus synchronization and fertility after synchronization of 60 multiparous Mashona goat does using intravaginal progesterone (P4) sponges (Group 1), norgestomet ear implants (Group 2), cloprostenol (Group 3), or a combination of P4 sponges and cloprostenol (Group 4) was compared with untreated does (Group 5). At the end of treatments, all does were mated to intact fertile bucks for 21 d. The number of does bred within 11 to 96 h was significantly higher (P < 0.05) in the treated groups than the untreated control, with rates of 80, 80, 64, 67 and 30% for Groups 1 to 5, respectively. There were no differences (P > 0.05) among treated does. Kidding rates ranged from 64 to 83% but were not different (P > 0.05) between groups. Prolificacy and overall fecundity were similar (P > 0.05) among the groups. The results indicate that all 4 treatment methods were effective in synchronizing estrus and that none of the methods affected overall fertility of the does.


Case report of a coyote attack in Yellowstone National Park.
We report the case of an unprovoked coyote attack on a human visitor to Yellowstone National Park. Although the patient suffered only soft tissue injuries, unprovoked attacks are rarely reported in the medical literature. This case and plans on how to manage coyote attacks are discussed.


Temperature-controlled plasmid regulon associated with low calcium response in Yersinia pestis.
Both the low calcium response and virulence in Yersinia pestis strain KIM5 are mediated by genes located on the 75.4-kilobase plasmid pCD1. The results presented here demonstrate the existence of two new genetic loci of pCD1 whose expression is regulated in response to temperature. Levels of transcription in the trtA and trtB loci were elevated 12- to 16-fold at 37 degrees C compared with levels of transcription at 30 degrees C. In addition, the absolute levels of transcription were the highest that have been reported for genes on pCD1. Mutations in trtB also abolished production of the V antigen. Thermal induction at these loci was dramatically reduced in strains harboring a Tn5 insertion in the lcrF locus of pCD1. lcrF lies 33 and 13 kilobases from the trtA and trtB loci, respectively. Thus, lcrF is a positive regulatory gene responsible for temperature-induced transcription of genes required for the low calcium response.


Minocycline and Diacetyl Minocycline Eye Drops Reduce Ocular Neovascularization in Mice.
To evaluate the efficacy of minocycline and a novel, modified minocycline analogue that lacks antimicrobial action, diacetyl minocycline (DAM), on choroidal neovascularization (CNV) in mice of both sexes. CNV was induced via laser injury in female and male C57BL/6J mice. Minocycline, DAM, or saline was administered via topical eye drops twice a day for 2 weeks starting the day after laser injury. CNV volume was measured using immunohistochemistry labeling and confocal microscopy. Minocycline reduced lesion volume by 79% (P ≤ 0.0004) in female and male mice. DAM reduced lesion volume by 73% (P ≤ 0.001) in female and male mice. There was no significant difference in lesion volume between minocycline and DAM treatment groups or between female and male mice. Both minocycline and DAM eye drops significantly reduced laser-induced CNV lesion volume in female and male mice. While oral tetracyclines have been shown to mitigate pathologic neovascularization in both preclinical studies and clinical trials, the present data are the first to suggest that tetracycline derivatives may be effective to reduce pathologic CNV when administered via topical eye drops. However, the action is unrelated to antimicrobial action. Targeted delivery of these medications via eye drops may reduce the potential for systemic side effects. Topical administration of minocycline and/or DAM via eye drops may represent a novel therapeutic strategy for disorders involving pathologic CNV.


[Frequency of detection of anaerobic microorganisms in the maxillary sinuses of patients with different forms of chronic maxillary sinusitis].
The aim of the investigation was to determine the frequency of detection of anaerobic microorganisms in the maxillary sinuses of patients with different forms of chronic maxillary sinusitis. 36 patients were examined. Fence clinical material was carried out from the walls of the maxillary sinus with transport tubes Ames during "Operation maxillary sinusotomy." In order to create anaerobic conditions, we used a set of equipment and supplies (manufacturer bio Mérieux, France) of a company bio Merieux in Ukraine--"Company Diaveritas." It was found that the presence of anaerobic infection is not typical for chronic sinusitis of the odontogenic origin. A wider range of pathogens (60%), observed in chronic odontogenic sinusitis with the presence of a foreign body in the lumen of the sinus. In the mixed associations set aside 50% of anaerobic flora.


Upregulation of CDKN2A and suppression of cyclin D1 gene expressions in ACTH-secreting pituitary adenomas.
Cushing's disease (CD) is usually caused by ACTH-secreting pituitary microadenomas, while silent corticotroph adenomas (SCA) are macroadenomas without Cushingoid features. However, the molecular mechanism(s) underlying their different tumor growth remains unknown. The aim of the current study was to evaluate and compare the gene expression profile of cell cycle regulators and cell growth-related transcription factors in CD, SCA, and non-functioning adenomas (NFA). Tumor tissue specimens resected from 43 pituitary tumors were studied: CD (n=10), SCA (n=11), and NFA (n=22). The absolute transcript numbers of the following genes were quantified with real-time quantitative PCR assays: CDKN2A (or p16(INK4a)), cyclin family (A1, B1, D1, and E1), E2F1, RB1, BUB1, BUBR1, ETS1, and ETS2. Protein expressions of p16 and cyclin D1 were semi-quantitatively evaluated by immunohistochemical study. CDKN2A gene expression was about fourfold greater in CD than in SCA and NFA. The gene expressions of cyclins D1, E1, and B1, but not of A1, in CD were significantly suppressed than those in NFA. Cyclin D1 gene expression positively correlated with cyclins B1 and E1. The gene expressions of E2F1, RB1, BUB1, BUBR1, ETS1, and ETS2 did not differ between each group. Positive immunostaining for p16 and negative immunostaining for cyclin D1 were more frequent in CD than in NFA; there were positive correlations between mRNA and protein expressions of p16 and cyclin D1. Thus, it is suggested that upregulated CDKN2A with the concomitant downregulated cyclin gene family is partly involved in the small size of ACTH-secreting adenoma.


Functional outcomes after fixation of "terrible triad" elbow fracture dislocations.
Historically, the published literature on "terrible triad" injuries has shown a high rate of unacceptable results. The use of systematic treatment protocols may improve functional outcome. The authors performed a retrospective study of all patients aged 18 years or older who underwent surgical treatment for "terrible triad" elbow fracture dislocation at their institution over a period 7 years. Surgical treatment involved fixation or replacement of the radial head, repair of the anterior capsule or coronoid fracture in most cases, and repair of the lateral collateral ligament. Outcomes included grip strength, range of motion, Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score, and a visual analog score for pain as well as radiographic assessment of arthritis, maintenance of reduction, and development of heterotopic ossification. Eighteen patients were identified and 11 enrolled. Seven patients had suture fixation of the coronoid fragment and anterior capsule, 2 had screw fixation, and 2 had no repair of the coronoid. The radial head was replaced in 9 patients and repaired in 1, and a fracture fragment was excised in another. The average follow-up was 38 months. The average arc of motion of the injured elbow was 112° and that of the contralateral elbow was 142°. The average DASH score was 19.7 (scale, 0-100). The average visual analog score for pain was 2.2 (scale, 0-10). No patients had recurrent elbow instability. Three patients underwent further surgical procedures, all for loss of motion. The authors concluded that a systematic approach to the fixation of "terrible triad" elbow fracture dislocations can provide predictable elbow stability and functional range of motion in the medium term.


Dermatoglyphics and the persistence of 'Mongolism'.
In 1961, a prestigious group of medical researchers called on their colleagues to stop using the language of 'Mongolism' to describe people with what we now call 'Down's syndrome' (or Trisomy 21). This call responded to new knowledge about the biological basis of Down's syndrome: rather than the product of racial degeneration, as had been hypothesized in the 19th century, the condition was the result of an extra chromosome, dubbed '21'. Yet, despite this plea, the terms 'Mongol' and 'Mongolism' continued in scientific use through the 1960s. Drawing on published and archival materials, I argue that the new knowledge about chromosomes did not rupture older patterns of scientific practice or interpretation, and with them, older terminological habits. The persistence of the language of Mongolism reflects the continuity of a network of older approaches to interpreting the condition within the community of human and medical geneticists, including an enduring diagnostic and interpretive technology, dermatoglyphics. Old networks were not supplanted; they were re-aligned.


Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines.
Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. In this study high-level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) were created, and comparative genomic hybridisation was used to identify genomic regions associated with resistance to docetaxel. MCF-7 resistant cells showed an amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of chromosomes 6p, 10q11.2-qter and 12p. MDA-MB-231 resistant cells showed a gain of chromosomes 5p, 7q11.1-q35, 9, and loss of chromosomes 4, 8q24.1-qter, 10, 11q23.1-qter, 12q15-q24.31, 14q and 18. Whole chromosome paints confirmed these findings. Amplification of 7q21 and loss of 10q may represent a common mechanism of acquired docetaxel resistance in breast cancer cells. This study is the first description of a genomic approach specifically to identify genomic regions involved in resistance to docetaxel.


Detecting copy number variation with mated short reads.
The development of high-throughput sequencing (HTS) technologies has opened the door to novel methods for detecting copy number variants (CNVs) in the human genome. While in the past CNVs have been detected based on array CGH data, recent studies have shown that depth-of-coverage information from HTS technologies can also be used for the reliable identification of large copy-variable regions. Such methods, however, are hindered by sequencing biases that lead certain regions of the genome to be over- or undersampled, lowering their resolution and ability to accurately identify the exact breakpoints of the variants. In this work, we develop a method for CNV detection that supplements the depth-of-coverage with paired-end mapping information, where mate pairs mapping discordantly to the reference serve to indicate the presence of variation. Our algorithm, called CNVer, combines this information within a unified computational framework called the donor graph, allowing us to better mitigate the sequencing biases that cause uneven local coverage and accurately predict CNVs. We use CNVer to detect 4879 CNVs in the recently described genome of a Yoruban individual. Most of the calls (77%) coincide with previously known variants within the Database of Genomic Variants, while 81% of deletion copy number variants previously known for this individual coincide with one of our loss calls. Furthermore, we demonstrate that CNVer can reconstruct the absolute copy counts of segments of the donor genome and evaluate the feasibility of using CNVer with low coverage datasets.


[Chronic obstructive pulmonary disease--work-related disease].
Chronic obstructive pulmonary disease (COPD) can be induced by hazardous agents present in the work environment. It is estimated that employment in exposure to dust and irritant gases is responsible for 10 to 20% of COPD cases. The paper reviews the etiology (particularly the occupational risk factors) of the disease, its clinical symptoms, and diagnostic procedures. The significance of COPD in occupational medicine, especially in terms of prophylactic care of workers is also presented.


Ambient seismic wave field.
The ambient seismic wave field, also known as ambient noise, is excited by oceanic gravity waves primarily. This can be categorized as seismic hum (1-20 mHz), primary microseisms (0.02-0.1 Hz), and secondary microseisms (0.1-1 Hz). Below 20 mHz, pressure fluctuations of ocean infragravity waves reach the abyssal floor. Topographic coupling between seismic waves and ocean infragravity waves at the abyssal floor can explain the observed shear traction sources. Below 5 mHz, atmospheric disturbances may also contribute to this excitation. Excitation of primary microseisms can be attributed to topographic coupling between ocean swell and seismic waves on subtle undulation of continental shelves. Excitation of secondary microseisms can be attributed to non-linear forcing by standing ocean swell at the sea surface in both pelagic and coastal regions. Recent developments in source location based on body-wave microseisms enable us to estimate forcing quantitatively. For a comprehensive understanding, we must consider the solid Earth, the ocean, and the atmosphere as a coupled system.


A natural population of Helisoma duryi in Brazil.
A well established natural population of Helisoma duryi (Wetherby) was recently found in central Brazil, where it was introduced probably with aquatic plants conveyed by aquarists. A morphological description based on the observation of 10 specimens is presented, involving the shell, cephalopodal mass, mantle organs, reproductive system and buccal apparatus.


Computational screening of M/Cu core/shell nanoparticles and their applications for the electro-chemical reduction of CO2 and CO.
To improve the catalytic activity of copper nanoparticles (Cu NPs) in the electro-chemical catalysis of the CO2 reduction reactions (CO2RRs), the formation and use of core/shell nanoparticles (CSNPs) with Cu as the shell composite may be an effective way. Using Cu79 NP as the representative, we performed computational screening and confirmed four Mx@Cu79-x CSNPs that can stably exist. Then, the catalytic performance of the screened CSNPs was tested through first-principles calculations. The free energy profiles indicate that Fe19@Cu60 is more desirable for CO2RR catalysis due to its high selectivity for CO rather than HCOOH at a low potential. Moreover, when it electro-catalyzes CO2 into CH4, the Fe19@Cu60 CSNP exhibits much lower limiting potential (-0.58 V) compared with pure Cu79 NP (-0.86 V) or the Cu (211) surface (-0.70 V). Taking the cost into consideration, the Fe19@Cu60 CSNP is highly recommended as a promising electro-catalyst for CO2RRs. In addition, when CO is taken as the initial reactant to be reduced, all the screened CSNPs exhibit lower limiting potentials than Cu79 NP. From the view of material design, the significant weakening of CO binding originating from the change in the d-band center could be the reason why the formation of a core/shell structure will enhance the catalytic performance of Cu NPs in CO reduction.