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Clinical guidelines have emerged as an important tool for improving healthcare quality and controlling healthcare costs. However, they also have the potential to limit access to treatment and servi...

Networks provide a mathematically rich framework to represent social contacts sufficient for the transmission of disease. Social networks are often highly clustered and fail to be locally tree-like. In this paper, we study the effects of clustering on the spread of sequential strains of a pathogen using the generating function formulation under a complete cross-immunity coupling, deriving conditions for the threshold of coexistence of the second strain. We show that clustering reduces the coexistence threshold of the second strain and its outbreak size in Poisson networks, whilst exhibiting the opposite effects on uniform-degree models. We conclude that clustering within a population must increase the ability of the second wave of an epidemic to spread over a network. We apply our model to the study of multilayer clustered networks and observe the fracturing of the residual graph at two distinct transmissibilities., 9 pages, 5 figures

Background:Computer-Aided Drug Design has strongly accelerated the development of novel antineoplastic agents by helping in the hit identification, optimization, and evaluation.Results:Computational approaches such as cheminformatic search, virtual screening, pharmacophore modeling, molecular docking and dynamics have been developed and applied to explain the activity of bioactive molecules, design novel agents, increase the success rate of drug research, and decrease the total costs of drug discovery. Similarity, searches and virtual screening are used to identify molecules with an increased probability to interact with drug targets of interest, while the other computational approaches are applied for the design and evaluation of molecules with enhanced activity and improved safety profile.Conclusion:In this review are described the main in silico techniques used in rational drug design of antineoplastic agents and presented optimal combinations of computational methods for design of more efficient antineoplastic drugs.

An increasing elderly population in the United Kingdom has led to an increasing number of older patients with head and neck cancer, resulting in a greater demand for complex head and neck reconstructive surgery in this potentially high-risk age group. A possible perceived poorer tolerance to such major treatment risks under-treating some of these patients. The purpose of this study was to assess the outcomes in the elderly population (older than 80 years) who had undergone free flap reconstruction following head and neck cancer resection. A retrospective review of 127 patients was performed. Eighteen patients were 80 or older (14.2%) and 109 under 80 (85.8%). The elderly group experienced increased number of postoperative medical complications (p=0.01), but the surgical complications were not significantly different in the two groups (p=0.4). The average length of hospital stay was significantly longer in the older group (p=0.01). There was one flap failure during the study period, which belonged to the younger group of patients. Elderly patients undergoing free flap reconstruction experience an increased rate of postoperative medical complications resulting in an increased length of hospital stay. However, good surgical outcomes can still be achieved in this age group, and therefore age alone should not be considered as a primary factor in head and neck cancer management.

Introduction Increasingly, health care is delivered through a patient-centered model, and patients engage in shared decision-making with their medical providers. As a result, medical educators are placing more emphasis on patient-centered communication skills. However, few published curricula currently offer a comprehensive discussion of skills for providing patient-centered education (PCE), a key component of shared decision-making. We developed an interactive, two-session workshop aiming to improve students’ abilities to provide PCE. Methods Our workshop included didactic instruction, group discussion, and interactive simulations. The workshop was delivered to 50 clinical clerkship medical students. The first session concentrated on educating patients about their diagnoses, while the second session focused on providing patients with information about medications and other treatments. We used detailed and realistic role-play exercises as a core tool for student practice and demonstration of confidence. To evaluate the workshop, we used pre- and postsurveys. Results The sessions were well received by students, who strongly agreed both before and after the workshop that PCE was an important skill. Students also strongly agreed that the role-play exercises were an effective tool for learning PCE. They demonstrated significant improvements in their confidence to name important elements of PCE and to deliver PCE in the future. Discussion This workshop fills a curricular gap in offering a comprehensive and interactive curriculum for improving students’ abilities to provide critical PCE. The format and content should be easily adaptable to various disciplines, learners, and teaching modalities.

We describe three machine learning models submitted to the 2019 Solubility Challenge. All are founded on tree-like classifiers, with one model being based on Random Forest and another on the related Extra Trees algorithm. The third model is a consensus predictor combining the former two with a Bagging classifier. We call this consensus classifier Vox Machinarum, and here discuss how it benefits from the Wisdom of Crowds. On the first 2019 Solubility Challenge test set of 100 low-variance intrinsic aqueous solubilities, Extra Trees is our best classifier. One the other, a high-variance set of 32 molecules, we find that Vox Machinarum and Random Forest both perform a little better than Extra Trees, and almost equally to one another. We also compare the gold standard solubilities from the 2019 Solubility Challenge with a set of literature-based solubilities for most of the same compounds.

The third flight of the High-Resolution Coronal Imager (Hi-C 2.1) occurred on May 29, 2018, the Sounding Rocket was launched from White Sands Missile Range in New Mexico. The instrument has been modified from its original configuration (Hi-C 1) to observe the solar corona in a passband that peaks near 172 Angstrom and uses a new, custom-built low-noise camera. The instrument targeted Active Region 12712, and captured 78 images at a cadence of 4.4 sec (18:56:22 - 19:01:57 UT; 5 min and 35 sec observing time). The image spatial resolution varies due to quasi-periodic motion blur from the rocket; sharp images contain resolved features of at least 0.47 arcsec. There are coordinated observations from multiple ground- and space-based telescopes providing an unprecedented opportunity to observe the mass and energy coupling between the chromosphere and the corona. Details of the instrument and the data set are presented in this paper., Comment: 26 pages, 15 figures, submitted to Solar Physics

This paper analyses one year’s worth of residential load data from 300 homes, as produced publicly by a Sydney- based network supply. The data relates to residences that have a mixture of normal load, controlled load (off-peak water heating) and a considerable proportion also having roof-top solar PV. The objectives of this analysis are to determine the improved “prosumer” response by altering the off-peak controlled load switching times by using “excess” solar PV energy in the middle of the day to pre-heat the controlled load. A sample of 40 homes out of the 300 total is taken, as this amount represents a typical low voltage distributor load. The second set of analyses is done by simulating the impact of having storage at each solar PV owner’s premises.

Coventry Cathedral was completed in the early 1960s and has some prestressed concrete elements to resist lateral thrust from the roof. Other prestressed structures of a similar age have had corrosion problems and this has drawn attention to the fact that there is little publicly available information about the structural system at Coventry. This paper addresses that issue and is in three sections. The first summarises the four different prestressing systems in the Cathedral and estimates the amount of prestress and its purpose in each location. By placing the information in the public domain it will be useful for both historians of church architecture and engineers in future generations who may have to work on the building. Although there is no evidence of corrosion in the building at the moment, it is impossible to inspect the existing tendons, so the second section considers what might happen to the structure if corrosion of the tendons were to occur. It is concluded that very little warning of failure would be given, which would be especially important for the tendons over the baptistry window and those in the nave ties. The final section considers what could be monitored to give as much warning as possible about future problems. The effects of loss of an individual tendon, which would not by itself be sufficient to cause failure of the structure, would cause only very small strains that would be difficult to distinguish from the background strains caused by temperature change. Many of the principles discussed in the second and third sections would be applicable to many other prestressed concrete structures.

The unprecedented impact of COVID-19 has raised concern for the potential of increased suicides due to a convergence of suicide risk factors. We obtained suicide mortality data to assess completed suicides during the period of strict stay-at-home quarantine measures in Connecticut and compared this data with previous years. While the total age-adjusted suicide mortality rate decreased by 13% during the lockdown period compared with the 5-year average, a significantly higher proportion of suicide decedents were from racial minority groups. This finding may provide early evidence of a disproportionate impact from the social and economic challenges of COVID-19 on minority populations.

Current risk assessment models for surgical site occurrence (SSO) and surgical site infection (SSI) after open ventral hernia repair (VHR) have limited external validation. Our aim was to determine (1) whether existing models stratify patients into groups by risk and (2) which model best predicts the rate of SSO and SSI.Patients who underwent open VHR and were followed for at least 1 mo were included. Using two data sets-a retrospective multicenter database (Ventral Hernia Outcomes Collaborative) and a single-center prospective database (Prospective)-each patient was assigned a predicted risk with each of the following models: Ventral Hernia Risk Score (VHRS), Ventral Hernia Working Group (VHWG), Centers for Disease Control and Prevention Wound Class, and Hernia Wound Risk Assessment Tool (HW-RAT). Patients in the Prospective database were also assigned a predicted risk from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Areas under the receiver operating characteristic curve (area under the curve [AUC]) were compared to assess the predictive accuracy of the models for SSO and SSI. Pearson's chi-square was used to determine which models were able to risk-stratify patients into groups with significantly differing rates of actual SSO and SSI.The Ventral Hernia Outcomes Collaborative database (n = 795) had an overall SSO and SSI rate of 23% and 17%, respectively. The AUCs were low for SSO (0.56, 0.54, 0.52, and 0.60) and SSI (0.55, 0.53, 0.50, and 0.58). The VHRS (P = 0.01) and HW-RAT (P 0.01) significantly stratified patients into tiers for SSO, whereas the VHWG (P 0.05) and HW-RAT (P 0.05) stratified for SSI. In the Prospective database (n = 88), 14% and 8% developed an SSO and SSI, respectively. The AUCs were low for SSO (0.63, 0.54, 0.50, 0.57, and 0.69) and modest for SSI (0.81, 0.64, 0.55, 0.62, and 0.73). The ACS-NSQIP (P 0.01) stratified for SSO, whereas the VHRS (P 0.01) and ACS-NSQIP (P 0.05) stratified for SSI. In both databases, VHRS, VHWG, and Centers for Disease Control and Prevention overestimated risk of SSO and SSI, whereas HW-RAT and ACS-NSQIP underestimated risk for all groups.All five existing predictive models have limited ability to risk-stratify patients and accurately assess risk of SSO. However, both the VHRS and ACS-NSQIP demonstrate modest success in identifying patients at risk for SSI. Continued model refinement is needed to improve the two highest performing models (VHRS and ACS-NSQIP) along with investigation to determine whether modifications to perioperative management based on risk stratification can improve outcomes.

By measuring the time of flight of scattered X-ray photons, the point of interaction, assuming a single scatter, can be determined, providing 3-D information about an object under inspection. This paper describes experimental ToF Compton scatter measurements conducted at the versatile electron linear accelerator (VELA), a picosecond pulsewidth electron source situated in Daresbury, U.K. The ToF of scattered X-ray photons was measured using a CeBr3 detector, and a full width at half maximum (FWHM) of between 29 and 36 cm was achieved with a 5-cm-thick plastic test object. By implementing a low-energy cutoff, the FWHM was reduced to between 12 and 26 cm. Two test objects placed in series with a 50-cm space between were separable in the data after applying the low energy cutoff.

Jellyfish can cause significant losses to the aquaculture industry. This report describes the clinical presentation and pathology caused by the mauve stinger jellyfish Pelagia noctiluca (Forsskal, 1775) in cultured Atlantic salmon Salmo salar L. in Ireland and highlights the potential consequences and need for descriptive pathology of such interactions. P. noctiluca is a member of the cnidarian class Scyphozoa (Order Semaeostomeae; Family Pelagiidae) and has worldwide distribution through the warm and temperate waters of the marine environment. This golden brown to purple jellyfish species lacks the benthic polyp stage and has a primarily pelagic habitat, although ocean currents bring it closer to coastal waters. P. noctiluca is frequently observed from the west coast of Ireland especially during the autumn months, but large aggregations are not commonly reported. In a jellyfish survey carried out around Ireland in 2009, P. noctiluca was the most abundant species found, accounting for 93% of the overall catch (total wet weight of gelatinous species) (Bastian et al. 2011). Its distribution and density were found to be heterogeneous, with great variation between regions (apparent North-South gradient in density) and sampling points (Bastian et al. 2011). When in contact with a fish farm, small jellyfish can pass through the nets, while bigger individuals tend to break up into pieces still capable of stinging the fish. In jellyfish blooms, affected fish can suffer from hypoxia, mechanical damage and toxicity via nematocysts discharge (Baxter et al. 2011a; Rodger, Henry & Mitchell 2011). In 2013, large swarms of P. noctiluca were observed intermittently in several Northern and Southern farms in the west coast of Ireland from the beginning of August to mid-November. Jellyfish presence was determined by visual observations from boat and cages and by divers during removal of mortalities. Zooplankton sampling through vertical net tows and posterior species identification was also carried out. The diagnosis of the jellyfish species involved was based on the morphological features described in detail by Russell (1970). Jellyfish appeared in the vicinity and inside cages (Fig. 1a), and associated mortalities ranged from

Salivary gland cancers are rare and represent approximately 5% of all head and neck cancers and only 0.3% of all malignancies. The majority (75%) of salivary gland tumors occur in the parotid gland, and while benign lesions are more common, mucoepidermoid carcinoma (MEC) makes up 40–50% of malignant parotid gland tumors. No randomized controlled trials exist regarding the role of adjuvant radiation for patients who undergo surgical resection of low-grade MECs. Herein, we report two cases of successful postoperative radiation therapy in low-grade, pT2N0 MEC of the parotid gland. The role of adjuvant radiation therapy for patients with MEC of the parotid gland is based on data from institution reviews and lacks data from randomized controlled trials. Per our review of the literature, the pathological findings of positive surgical margins and/or perineural invasion in two patients with low-grade MEC of the parotid gland warranted adjuvant radiation for improved local control after partial parotidectomy. Both patients tolerated postoperative radiation therapy with only mild side effects and, at last follow-up, five years after completion of therapy, had no clinical or radiographic evidence of either local recurrence or distant metastasis.

In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in conjunction with circular fingerprints on a large data set of bioactive compounds extracted from ChEMBL, covering 894 human protein targets with more than 155,000 ligand-protein pairs. This data set is also provided as a benchmark data set for future target prediction methods due to its size as well as the number of bioactivity classes it contains. In addition to evaluating the methods, different performance measures were explored. This is not as straightforward as in binary classification settings, due to the number of classes, the possibility of multiple class memberships, and the need to translate model scores into "yes/no" predictions for assessing model performance. Both algorithms achieved a recall of correct targets that exceeds 80% in the top 1% of predictions. Performance depends significantly on the underlying diversity and size of a given class of bioactive compounds, with small classes and low structural similarity affecting both algorithms to different degrees. When tested on an external test set extracted from WOMBAT covering more than 500 targets by excluding all compounds with Tanimoto similarity above 0.8 to compounds from the ChEMBL data set, the current methodologies achieved a recall of 63.3% and 66.6% among the top 1% for Naïve Bayes and Parzen-Rosenblatt Window, respectively. While those numbers seem to indicate lower performance, they are also more realistic for settings where protein targets need to be established for novel chemical substances.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial resistance and vessel remodeling. Patients living with human immunodeficiency virus-1 (HIV-1) have an increased susceptibility to develop severe pulmonary hypertension (PH) irrespective of their CD4+ lymphocyte counts. While the underlying cause of HIV-PAH remains unknown, the interaction of HIV-1 proteins with the vascular endothelium may play a critical role in HIV-PAH development. Hypoxia promotes PH in experimental models and in humans, but the impact of HIV-1 proteins on hypoxia-induced pulmonary vascular dysfunction and PAH has not been examined. Therefore, we hypothesize that the presence of HIV-1 proteins and hypoxia synergistically augment the development of pulmonary vascular dysfunction and PH. We examined the effect of HIV-1 proteins on pulmonary vascular resistance by measuring pressure-volume relationships in isolated lungs from wild-type (WT) and HIV-1 Transgenic (Tg) rats. WT and HIV-1 Tg rats were exposed to 10% O2 for four weeks to induce experimental pulmonary hypertension to assess whether HIV-1 protein expression would impact the development of hypoxia-induced PH. Our results demonstrate that HIV-1 protein expression significantly increased pulmonary vascular resistance (PVR). HIV-1 Tg mice demonstrated exaggerated pulmonary vascular responses to hypoxia as evidenced by greater increases in right ventricular systolic pressures, right ventricular hypertrophy and vessel muscularization when compared to wild-type controls. This enhanced PH was associated with enhanced expression of HIF-1α and PCNA. In addition, in vitro studies reveal that medium from HIV-infected monocyte derived macrophages (MDM) potentiates hypoxia-induced pulmonary artery endothelial proliferation. These results indicate that the presence of HIV-1 proteins likely impact pulmonary vascular resistance and exacerbate hypoxia-induced PH.

Background. Obesity rates for pediatric acute lymphocytic leukemia (ALL) survivors vary from 11% to 57%. Researching dietary behaviors may identify dietary risks leading to obesity and opportunities for intervention. Objective. To evaluate the relationship between caloric and macronutrient intake on the incidence of obesity in pediatric ALL. Design/setting/participants. Retrospectively reviewed data of 142 participants was examined. Participants were grouped into categories based on body mass index (BMI) for adults and Centers for Disease Control and Prevention growth charts for children. Twenty-four-hour food recall records were reviewed to assess dietary intake. Confounding factors and caloric/macronutrient intake were compared across obesity classes. Main outcome measurements. Macronutrient levels were compared between groups. Descriptive data examined. BMI at enrollment on BONEII, age at diagnosis, ethnicity, gender, corticosteroid use, cranial radiation therapy, and standard/high risk. ALL group. Results. Thirty-nine percent of participants were overweight/obese. ALL survivors who consumed a higher percentage of their calories from protein were more likely to be underweight/normal weight while participants who consumed more calories and total carbohydrates were more likely to be overweight/obese. There was no relationship with the other factors examined. Conclusion. Dietary interventions should be designed to ensure patients consume adequate amounts of protein while limiting portion sizes and carbohydrate-based snacks.

Gill health and disease in farmed Atlantic salmon (Salmo salar) were studied at a marine site on the west coast of Ireland. Fish were sampled on a regular basis during the summer and autumn of 2009. A novel histopathological scoring system was devised to give a semi-quantitative measure of gill pathology. The index criteria for gill histopathology were lamellar hyperplasia, lamellar fusion, circular anomalies (necrosis or sloughing) and lamellar oedema, a score from 0 to 3 being assigned for each parameter. Ancillary criteria, such as hypertrophy, haemorrhage and the presence of specific pathogens, were assigned a score of 0 or 1. Environmental monitoring undertaken included zooplankton and phytoplankton sampling, as well as temperature and oxygen recordings for the site. Epitheliocystis was frequently observed at low levels but was not associated with any significant gill pathology. Clinically significant gill pathology was observed on one occasion during the sampling period, coinciding with the occurrence of Pelagia noctiluca, Muggiaea atlantica and Solmaris corona. Throughout the longitudinal study, the scoring system provided an accurate and effective means of assessing gill health, demonstrating the ability of this practical tool to be used in future studies of gill health and disease.

Background A multi-center study was conducted to evaluate the Bio-Rad GS HIV Combo Ag/Ab EIA, a 4th generation HIV-1/HIV-2 assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma in adult and pediatric populations. Objectives The objectives of the study were to assess assay performance for the detection of acute HIV infections; sensitivity in known HIV positive samples; percent agreement with HIV status; specificity in low and high risk individuals of unknown HIV status; and to compare assay performance to a 3rd generation HIV assay. Study design The evaluation included testing 9150 samples at four U.S. clinical trial sites, using three kit lots. Unlinked samples were from routine testing, repositories or purchased from vendors. Results GS HIV Combo Ag/Ab EIA detection in samples from individuals in two separate populations with acute HIV infection was 95.2% (20/21) and 86.4% (38/44). Sensitivity was 100% (1603/1603) in known antibody positive [HIV-1 Groups M and O, and HIV-2] samples. HIV p24 antigen detection was 100% (53/53) in HIV-1 culture supernatants. HIV-1 seroconversion panel detection improved by a range of 0–20 days compared to a 3rd generation HIV test. Specificity was 99.9% (5989/5996) in low risk, 99.9% (959/960) in high risk and 100% (100/100) in pediatric populations. Conclusion The GS HIV Combo Ag/Ab EIA significantly reduced the diagnostic window when compared to the 3rd generation screening assay, enabling earlier diagnosis of HIV infection. The performance parameters of the Bio-Rad GS HIV Combo Ag/Ab EIA are well suited for use in HIV diagnostic settings.

The central idea of supervised classification in chemoinformatics is to design a classifying algorithm that accurately assigns a new molecule to one of a set of predefined classes. Tipping has devised a classifying scheme, the Relevance Vector Machine (RVM), which is in terms of sparsity equivalent to the Support Vector Machine (SVM). However, unlike SVM classifiers, the RVM classifiers are probabilistic in nature, which is crucial in the field of decision making and risk taking. In this work, we investigate the performance of RVM binary classifiers on classifying a subset of the MDDR data set, a standard molecular benchmark data set, into active and inactive compounds. Additionally, we present results that compare the performance of SVM and RVM binary classifiers.

Objectives/Hypothesis: Monopolar cautery is the most commonly used technique for tonsillectomy. The aim of the present study is to compare postoperative pain using a new technology, PlasmaKnife tonsillectomy (PKT), in comparison with monopolar cautery tonsillectomy (MCT). Study Design: Prospective, randomized, single-blinded, self-controlled study using paired organs. Methods: Thirty-two adult patients, aged 18 to 30 years, scheduled for tonsillectomy for recurrent tonsillitis were included. Patients were randomly assigned to undergo PKT on one side and MCT on the opposite side. The primary outcome was self-rated daily pain assessed by using a 10-point scale. Patients were provided 21-day pain diaries and were phoned twice weekly by a research assistant to assess pain and remind them to complete diaries. Secondary outcomes included comparisons of operative time, blood loss, and postoperative complications. Results: Repeated measures analysis of variance comparing PKT to MCT during the 21-day postoperative period revealed no difference in postoperative pain between the two groups (P = .131). In addition, total operative time (P = .276) and blood loss (P = .418) did not differ significantly between PKT and MCT. Conclusions: Adult subjects undergoing PKT do not experience less postoperative pain in comparison to MCT.

Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic drugs and can affect many cell types. It is characterized by the excess accumulation of phospholipids and is most reliably identified by electron microscopy of cells revealing the presence of lamellar inclusion bodies. The development of phospholipidosis can cause a delay in the drug development process, and the importance of computational approaches to the problem has been well documented. Previous work on predictive methods for phospholipidosis showed that state of the art machine learning methods produced the best results. Here we extend this work by looking at a larger data set mined from the literature. We find that circular fingerprints lead to better models than either E-Dragon descriptors or a combination of the two. We also observe very similar performance in general between Random Forest and Support Vector Machine models.

Motivation: Accurately predicting the binding affinities of large sets of diverse protein–ligand complexes is an extremely challenging task. The scoring functions that attempt such computational prediction are essential for analysing the outputs of molecular docking, which in turn is an important technique for drug discovery, chemical biology and structural biology. Each scoring function assumes a predetermined theory-inspired functional form for the relationship between the variables that characterize the complex, which also include parameters fitted to experimental or simulation data and its predicted binding affinity. The inherent problem of this rigid approach is that it leads to poor predictivity for those complexes that do not conform to the modelling assumptions. Moreover, resampling strategies, such as cross-validation or bootstrapping, are still not systematically used to guard against the overfitting of calibration data in parameter estimation for scoring functions. Results: We propose a novel scoring function (RF-Score) that circumvents the need for problematic modelling assumptions via non-parametric machine learning. In particular, Random Forest was used to implicitly capture binding effects that are hard to model explicitly. RF-Score is compared with the state of the art on the demanding PDBbind benchmark. Results show that RF-Score is a very competitive scoring function. Importantly, RF-Score's performance was shown to improve dramatically with training set size and hence the future availability of more high-quality structural and interaction data is expected to lead to improved versions of RF-Score. Contact: pedro.ballester@ebi.ac.uk; jbom@st-andrews.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

This paper presents a simulation study based on actual load, sunshine and wind data. A distribution feeder simulation model was constructed using this data to determine what potential benefit embedded wind, solar and storage elements could give to the distribution network. The results were compared to earlier studies. It was discovered that over the past 5–10 years, the hot weather peak load has extended from 3 pm to 6 pm and that a more northwesterly orientation of solar panels is of assistance. It was also found that wind is of little assistance in hot weather peaks, in contrast to data for the NSW central tablelands region; however solar contributes at least 50% of its nominal peak capacity. As hot weather peaks are now extending into the early evening, it was found that storage would be of great benefit and would enhance the use of renewable energy sources. As part of the feeder model, the optimal method of Var control from the embedded sources was also studied.

The acute respiratory distress syndrome (ARDS) is a severe form of acute edematous lung injury characterized by noncardiogenic pulmonary edema and flooding of the alveolar airspaces with proteinaceous fluid. ARDS develops in response to inflammatory stresses including sepsis, trauma, gastric aspiration, pneumonia and massive blood transfusions (Ware and Matthay, 2000). Originally described in 1967 (Ashbaugh et al., 1967), ARDS is characterized by alveolar epithelial and endothelial barrier disruption, surfactant dysfunction, and intense inflammation that, in concert, produce profound derangements in gas exchange and severe respiratory failure. Although a great deal has been learned about the underlying pathophysiology of this syndrome in the past four decades, our treatment remains essentially supportive and despite aggressive ICU care and mechanical ventilation, the mortality rate for ARDS remains unacceptably high at 40–60% (Rubenfeld et al., 2005;Ware and Matthay, 2000). An important clue to which patients are at greater risk for developing ARDS has been uncovered in recent epidemiologic studies demonstrating a link between alcohol abuse and acute lung injury (ALI), including the landmark study in 1996 that first identified an independent connection between alcohol abuse and ARDS (Moss et al., 1996). A more recent study confirmed those initial findings and determined that in individuals with septic shock, the relative risk of ARDS in alcoholic patients versus nonalcoholic patients was 3.7:1 (Moss et al., 2003). If these findings are extrapolated to the population at large, then alcohol abuse contributes to the development of ARDS in tens of thousands of patients in the U.S. each year. Alveolar epithelial barrier dysfunction is a prominent feature of ARDS. The maintenance of a fluid-free alveolar space is critical for facilitating normal gas exchange. A pathological hallmark of ALI/ARDS is heterogeneous damage of the alveolar epithelium, with complete loss of the epithelial surface in some areas but with other alveoli relatively intact. Therefore, at a cellular level the extent of the alveolar epithelial damage may not be as widespread or as uniform as the chest radiograph might suggest, and preservation and repair of the alveolar epithelium are keys to survival. In fact, patients with impaired alveolar epithelial fluid clearance are three times more likely to die from ALI/ARDS than patients with a maximal ability to clear lung fluid (Sznajder, 2001; Ware and Matthay, 2001). However, more than 85% of patients with ALI/ARDS have at least a partial defect in lung fluid clearance (Ware and Matthay, 2001). The ability of the lung to clear fluid away from the alveolar space and into the pulmonary circulation is largely dependent on active Na+ transport by the alveolar epithelium; for review, see (Morty et al., 2007). Na+ uptake at the apical side of the alveolar epithelium is mediated by amiloride-sensitive Na+ channels (ENaC), whereas Na+ is pumped out of the epithelial cells at the basolateral side by the Na,K-ATPase. The Na,K-ATPase belongs to the family of P-type ATPases and the functional enzyme consists of α and β subunits (Lingrel et al., 1994a–c; Sweadner, 1989). Multiple isoforms of both the α and β subunits have been reported (Lingrel et al., 1994b; Therien and Blostein, 2000). The catalytic α subunit contains binding sites for ATP as well as the Na,K-ATPase inhibitor, ouabain; for review, see (Kaplan, 2002). The alveolar epithelium expresses both α1 and α2 subunits (Borok et al., 2002; Ridge et al., 1997, 2003). The β subunit regulates activity and proper membrane localization of the α subunit (Factor et al., 1998; Geering, 1991; Kaplan, 2002; Therien and Blostein, 2000; Thome et al., 2001). Chronic alcohol ingestion increases ENaC density on the apical side of alveolar epithelial cells (Guidot et al., 2000b), and acute alcohol administration (a single dose) to rats decreases Na,K-ATPase activity (Aytacoglu et al., 2006; Rodrigo et al., 2002). However, to our knowledge the effects of chronic alcohol ingestion on the expression of Na,K-ATPase in the lung has not been determined. This critical evidence is necessary to support the aforementioned explanation as to why the otherwise healthy alcoholic lung is not edematous at baseline. Therefore, in this current study we sought to determine whether or not chronic alcohol ingestion increased the expression of Na,K-ATPase within the lung.

Mussa and Glen would like to thank Unilever for financial support, whereas Mussa and Mitchell thank the BBSRC for funding this research through grant BB/I00596X/1. Mitchell thanks the Scottish Universities Life Sciences Alliance (SULSA) for financial support. Background In a recent paper, Mussa, Mitchell and Glen (MMG) have mathematically demonstrated that the “Laplacian Corrected Modified Naïve Bayes” (LCMNB) algorithm can be viewed as a variant of the so-called Standard Naïve Bayes (SNB) scheme, whereby the role played by absence of compound features in classifying/assigning the compound to its appropriate class is ignored. MMG have also proffered guidelines regarding the conditions under which this omission may hold. Utilising three data sets, the present paper examines the validity of these guidelines in practice. The paper also extends MMG’s work and introduces a new version of the SNB classifier: “Tapered Naïve Bayes” (TNB). TNB does not discard the role of absence of a feature out of hand, nor does it fully consider its role. Hence, TNB encapsulates both SNB and LCMNB. Results LCMNB, SNB and TNB performed differently on classifying 4,658, 5,031 and 1,149 ligands (all chosen from the ChEMBL Database) distributed over 31 enzymes, 23 membrane receptors, and one ion-channel, four transporters and one transcription factor as their target proteins. When the number of features utilised was equal to or smaller than the “optimal” number of features for a given data set, SNB classifiers systematically gave better classification results than those yielded by LCMNB classifiers. The opposite was true when the number of features employed was markedly larger than the “optimal” number of features for this data set. Nonetheless, these LCMNB performances were worse than the classification performance achieved by SNB when the “optimal” number of features for the data set was utilised. TNB classifiers systematically outperformed both SNB and LCMNB classifiers. Conclusions The classification results obtained in this study concur with the mathematical based guidelines given in MMG’s paper—that is, ignoring the role of absence of a feature out of hand does not necessarily improve classification performance of the SNB approach; if anything, it could make the performance of the SNB method worse. The results obtained also lend support to the rationale, on which the TNB algorithm rests: handled judiciously, taking into account absence of features can enhance (not impair) the discriminatory classification power of the SNB approach. Publisher PDF

This paper discusses the experience obtained through the use of a simulator of a renewable energy system, in both grid-connect and stand-alone modes. A system containing wind, solar, energy storage and stand-by plant is modelled. The simulator calculates energy flows on an hourly basis, using actual typical daily loading, wind and solar distributions in the western Sydney area. In stand-alone mode, the model shows the relationship between improving system availability and component rating and system storage. It also shows a rapid ‘law of diminishing returns’ effect, whereby the objective of complete energy independence would, although theoretically attainable, be prohibitively expensive in practice without some sort of stand-by plant. The model was also used to demonstrate the potential gains of using predictive procedures, based on seasonal averages of wind, solar and load, to optimise the scheduling of stand-by plant or in the case of grid connection, grid interaction.

BACKGROUND The current study was conducted to evaluate the efficacy of paclitaxel, administered weekly or once every 3 weeks, in combination with oral estramustine phosphate (EMP) in patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL). METHODS Between February 1996 and February 2001, 23 patients with recurrent NHL were enrolled onto this Phase II trial. The median age for all patients was 65 years (range, 27–80 years). The initial 12 patients (who received a mean number of 2.4 prior treatments, including 1 patient who received a prior peripheral blood stem cell transplant) received paclitaxel at a dose of 175 mg/m2 given as a 3-hour intravenous infusion every 21 days. The next 11 patients (who received a mean number of 2.8 prior treatments, including 1 patient who received prior peripheral blood stem cell transplant) were registered (1 patient refused treatment) to receive paclitaxel at a dose of 80 mg/m2 as a 1-hour intravenous infusion weekly for 6 weeks of an 8-week cycle. All patients received EMP at a dose of 600 mg/m2 orally per day beginning the day prior to each dose of paclitaxel for a total of 3 days. RESULTS When paclitaxel was administered every 21 days, 4 partial responses were observed in 12 evaluable patients (33.3%). The median survival was 147 days. The median duration of response was 102 days (range, 42–127 days) and the median time to disease progression was 66 days. Grade 3 and Grade 4 neutropenia (according to the revised version of the Common Toxicity Criteria of the National Cancer Institute) were observed in 5 patients (42%) in this group. In an attempt to reduce the incidence of myelosuppression, paclitaxel dosing was changed to weekly dosing. In the cohort of patients receiving weekly paclitaxel, an objective response was reported to occur in 3 (1 complete response and 2 partial responses) of 11 evaluable patients (27%). The median survival was 132 days (range, 33–462 days). The median duration of response was 64 days and the median time to disease progression was 57 days. There was no significant difference noted between the cohort receiving paclitaxel three times weekly and those receiving paclitaxel weekly with regard to overall survival and time to disease progression (P = 0.7 and P = 0.8, respectively by the log-rank test). Grade 3 or 4 neutropenia was observed in only 2 of 11 patients (18%) in the weekly paclitaxel group. There were no significant differences noted in terms of thrombocytopenia, anemia, nausea, anorexia, or fatigue between the treatment groups. CONCLUSIONS Paclitaxel given once weekly or three times weekly, in combination with oral EMP, was found to have comparable efficacy in patients with recurrent NHL, with an overall response rate of 30%. The response rate was found to be higher than that reported in prior studies of paclitaxel as a single agent in the treatment of NHL, suggesting that EMP may enhance paclitaxel efficacy in patients with NHL. Hematologic toxicity was diminished when paclitaxel was administered on a weekly schedule. The minimal myelotoxicity of weekly paclitaxel makes this a potentially attractive agent for combination regimens for patients with recurrent/refractory NHL. Cancer 2004. © 2004 American Cancer Society.

Adequate muscle mass and function are critical for human health. Several types of skeletal muscle growth, including regeneration and growth after atrophy, can occur in the rehabilitative period after orthopaedic surgery. The molecular pathways regulating growth of skeletal muscle in adults are understood poorly. The role of calcineurin in regulating regeneration and growth of atrophied skeletal muscle is discussed. Understanding the molecular and cellular pathways that regulate such muscle growth may lead to the development of strategies to enhance muscle growth, thereby facilitating rehabilitation after orthopaedic surgery.

Background The purpose of this study was to identify issues important to patients in their decision-making, expectations, and satisfaction when seeking treatment for a ventral hernia. Study Design An exploratory qualitative study was conducted of adult patients with ventral hernias seeking care at a safety-net hospital. Two semi-structured interviews were conducted with each patient: before and 6 months after surgical consultation. Interviews were audiotaped, transcribed, and coded using latent content analysis until data saturation was achieved. Results Of patients completing an initial interview (n = 30), 27 (90%) completed follow-up interviews. Half of the patients were Spanish-speaking, one-third had a previous ventral hernia repair, and two-thirds underwent initial nonoperative management after surgical consultation. Patient-described factors guiding management decisions included impact on quality of life, primarily pain and limited function; overwhelming challenges to meeting surgical criteria, primarily obesity; and assuming responsibility to avoid recurrence. Patients were uninformed regarding potential poor outcomes and contributing factors, even among patients with a previous ventral hernia repair, with most attributing recurrence to inadequate self-management. Conclusions Understanding patients' perspective is crucial to engaging them as stakeholders in their care, addressing their concerns, and improving clinical and patient-centered outcomes. Patient reports suggest how care can be improved through developing more effective strategies for addressing patients' concerns during nonoperative management, preoperative risk reduction strategies that are sensitive to their sociodemographic characteristics, treatment plans that harness patients' willingness for self-management, and patient education and decision-making tools.

Carotid endarterectomy in very elderly patients remains controversial. We report our experience with this operation on 101 very elderly patients at the Baptist Heart Institute, a community hospital in Lexington, Kentucky. Ages ranged from 80 to 93 years with an average age of 86.5 years. There are 7 nonagenarians in this study. The indications included asymptomatic severe carotid artery stenosis in 29 (29.7%) patients and symptomatic disease in 72 patients (71.3%). Sixty eight percent of the patients had significant co-morbidity that included hypertension, diabetes mellitus, lipid disorders, previous stroke, previous carotid endarterectomy, coronary artery disease and previous myocardial infarctions. Thirty two percent of the patients had no significant past medical history. Two deaths occurred during hospitalizations (1.98%). One of these patients had carotid endarterectomy in conjunction with coronary artery bypass grafting. This patient suffered a stroke. The second death occurred as the result of respiratory failure. There was 1 perioperative infarct. From this study, we conclude that carotid endarterectomy can be performed safely in very elderly patients in a community hospital.

The management of concomitant coronary and carotid disease is controversial. We report our experience of simultaneous coronary artery bypass surgery and carotid artery endarterectomy on 70 consecutive patients (34 males and 36 females) with a mean age of 68 years. The oldest patient was 91 years old. The average percent of carotid artery stenosis was 86% (range 60%–99%). The average number of grafts per patient was 3.35 (range 1–6). Two patients experienced postoperative strokes (2.86%), 1 had a perioperative infarct (1.42%), and 4 died in the hospital (5.7%). The simultaneous approach offers the advantage of shorter hospital stays, decreased anesthesia exposure, and significant cost savings. The causes of death include stroke, renal failure, and bowel infarction. This review indicates the simultaneous approach has a higher incidence of adverse outcomes compared with elective carotid endarterectomy or elective coronary artery bypass surgery. These patients, however, are at significantly higher risk due to their poor medical conditions, extensive atheromatous disease, and often emergent medical condition.

Intro Langerhans cell histiocytosis (LCH) is a rare disease involving the proliferation of histiocytes in one or more organ systems. The presentation of LCH is more common in the pediatric population and rarely occurs within the adult population. Isolated lymph node involvement is an extremely rare presentation of the disease. The authors present a case of isolated lymph node LCH in an otherwise healthy adult female and discuss management strategies for these unusual findings. Methods A case report of a patient at a tertiary care facility in June 2014 is discussed. Results/Discussion The diagnosis, clinical course, and management strategies for isolated adult LCH are discussed and reviewed. Conclusion Langerhans cell histiocytosis rarely presents with isolated lymph node involvement in adults. Management and surveillance algorithms are discussed in this unusual case of seemingly benign lymphadenopathy.

The USNS Comfort (T-AH-20) is 1 of 2 United States Navy hospital ships. In 2011, she deployed to 9 countries in Central and South America including Jamaica, Peru, Colombia, Ecuador, Nicaragua, Guatemala, El Salvador, Costa Rica, and Haiti. Eight surgical specialties including otolaryngology were involved, for a combined total of about 150 cases per country. An advance team coordinated patients with the Host Nation to be seen for presurgical screening. Selected patients were then taken aboard the ship for surgery and recovered in either the ship’s intensive care unit or ward. They were then discharged prior to ship embarkment to the next country. A total of 95 otolaryngology cases were performed during 9 mission stops. The mean number of procedures performed was 12 per country, with thyroidectomy being the most common. A wide variety of general otolaryngology procedures were performed without significant complications, markedly impacting the quality of life in these underserved countries.

© 2014 ACPE. This paper analyses solar and load data for a typical western Sydney region and the impacts and benefits of embedded solar on the local distribution grid, and proposes a simple real and reactive power control routine of solar sources to avoid excess radial distributor voltage rise and feeder current and losses. The benefits of local storage are also discussed. This paper's conclusions are that significant amounts of solar generation can be accommodated on the proviso that the real and reactive powers of embedded sources are independently and fully controllable to avoid voltage rise and losses. In deep solar inflow situations some spilling of real power may be required. Local storage even as low as several hours will be of benefit.

Machine learning algorithms are generally developed in computer science or adjacent disciplines and find their way into chemical modeling by a process of diffusion. Though particular machine learning methods are popular in chemoinformatics and quantitative structure–activity relationships (QSAR), many others exist in the technical literature. This discussion is methods-based and focused on some algorithms that chemoinformatics researchers frequently use. It makes no claim to be exhaustive. We concentrate on methods for supervised learning, predicting the unknown property values of a test set of instances, usually molecules, based on the known values for a training set. Particularly relevant approaches include Artificial Neural Networks, Random Forest, Support Vector Machine, k-Nearest Neighbors and naive Bayes classifiers. WIREs Comput Mol Sci 2014, 4:468–481. How to cite this article: WIREs Comput Mol Sci 2014, 4:468–481. doi:10.1002/wcms.1183

We report the first study of traps in strained Si1−yCy random alloys grown on Si 〈1 0 0〉 substrates using chemical vapor deposition. Deep level transient spectroscopy (DLTS) measurements of n-type Schottky diodes fabricated on Si/Si1−yCy/Si heterostructures (y

Metal-oxide-semiconductor (MOS) capacitors fabricated on in situ doped n-type Si/Si1−x−yGexCy and Si/Si1−yCy epitaxial layers were used to study the conduction band offsets in these heterojunctions. The heterostructures were grown epitaxially in a rapid thermal chemical vapor deposition reactor. Si/Si1−x−yGexCy samples with a nominal Ge concentration of 20 at. % and carbon fractions up to 1.3 at. % were studied. Carbon fractions up to 1.6 at. % were studied for the Si/Si1−yCy samples. Gate oxides were formed by thermal oxidation of the Si cap at 750 °C. X-ray diffraction measurements confirm that the processing did not affect the strain in the layers. Devices exhibit well-behaved high frequency and quasistatic capacitance–voltage (C–V) characteristics indicating the high electronic quality of the material. Capacitance–voltage measurements performed over a range of temperatures were used to extract the band offsets. Confinement of electrons at the heterointerface is apparent in the C–V curves of the Si/Si1...

In May 1994 an outbreak of vomiting and diarrhoea occurred in a 28-bed long-stay ward for the mentally infirm. The predominant symptoms were vomiting, diarrhoea, malaise and abdominal pain lasting for approximately 12 h in most cases. The attack rate was 62% (13/21) for patients and 46% (16/35) for staff members. Infection control measures were implemented (containment of infectious individuals, hand hygiene among staff and environmental decontamination) and the ward was closed to admissions. Affected staff were excluded from contact with patients and their food until asymptomatic for 72 h. The outbreak lasted for 17 days. Faecal samples from nine symptomatic persons were negative for bacterial enteric pathogens, Giardia, Cryptosporidium and group A rotavirus. Electron microscopy of 12 faecal samples and one sample of vomitus revealed small round structured virus (SRSV) particles in one faecal sample. A further 30 faecal samples and seven vomitus samples were tested by reverse transcription polymerase chain reaction (RT-PCR) for SRSV of which 12 (40%) and 1 (14%) were positive respectively. Twenty-eight throat swabs from symptomatic and asymptomatic patients were collected, three (9.5%) of which were positive for SRSV by RT-PCR. Thirty-six environmental swabs were collected on the affected ward, and 11 (30%) were positive by RT-PCR. Positive swabs were from lockers, curtains and commodes and confined to the immediate environment of symptomatic patients. The distribution of contamination supports the rationale of cohorting sick patients.

Background In the last decade the standard Naive Bayes (SNB) algorithm has been widely employed in multi–class classification problems in cheminformatics. This popularity is mainly due to the fact that the algorithm is simple to implement and in many cases yields respectable classification results. Using clever heuristic arguments “anchored” by insightful cheminformatics knowledge, Xia et al. have simplified the SNB algorithm further and termed it the Laplacian Corrected Modified Naive Bayes (LCMNB) approach, which has been widely used in cheminformatics since its publication. In this note we mathematically illustrate the conditions under which Xia et al.’s simplification holds. It is our hope that this clarification could help Naive Bayes practitioners in deciding when it is appropriate to employ the LCMNB algorithm to classify large chemical datasets. Results A general formulation that subsumes the simplified Naive Bayes version is presented. Unlike the widely used NB method, the Standard Naive Bayes description presented in this work is discriminative (not generative) in nature, which may lead to possible further applications of the SNB method. Conclusions Starting from a standard Naive Bayes (SNB) algorithm, we have derived mathematically the relationship between Xia et al.’s ingenious, but heuristic algorithm, and the SNB approach. We have also demonstrated the conditions under which Xia et al.’s crucial assumptions hold. We therefore hope that the new insight and recommendations provided can be found useful by the cheminformatics community.

Background A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1 + 2 EIA and Siemens HIV 1/O/2 was also evaluated. Objective Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Study design Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. Results GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7–11 days earlier than the 3rd generation HIV antibody only EIAs. Conclusion Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7–11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations.