Parallel continuous simulated tempering and its applications in large-scale molecular simulations.
In this paper, we introduce a parallel continuous simulated tempering (PCST) method for enhanced sampling in studying large complex systems. It mainly inherits the continuous simulated tempering (CST) method in our previous studies [C. Zhang and J. Ma, J. Chem. Phys. 130, 194112 (2009); C. Zhang and J. Ma, J. Chem. Phys. 132, 244101 (2010)], while adopts the spirit of parallel tempering (PT), or replica exchange method, by employing multiple copies with different temperature distributions. Differing from conventional PT methods, despite the large stride of total temperature range, the PCST method requires very few copies of simulations, typically 2-3 copies, yet it is still capable of maintaining a high rate of exchange between neighboring copies. Furthermore, in PCST method, the size of the system does not dramatically affect the number of copy needed because the exchange rate is independent of total potential energy, thus providing an enormous advantage over conventional PT methods in studying very large systems. The sampling efficiency of PCST was tested in two-dimensional Ising model, Lennard-Jones liquid and all-atom folding simulation of a small globular protein trp-cage in explicit solvent. The results demonstrate that the PCST method significantly improves sampling efficiency compared with other methods and it is particularly effective in simulating systems with long relaxation time or correlation time. We expect the PCST method to be a good alternative to parallel tempering methods in simulating large systems such as phase transition and dynamics of macromolecules in explicit solvent.


Adaptive divergence with gene flow in incipient speciation of Miscanthus floridulus/sinensis complex (Poaceae).
Young incipient species provide ideal materials for untangling the process of ecological speciation in the presence of gene flow. The Miscanthus floridulus/sinensis complex exhibits diverse phenotypic and ecological differences despite recent divergence (approximately 1.59 million years ago). To elucidate the process of genetic differentiation during early stages of ecological speciation, we analyzed genomic divergence in the Miscanthus complex using 72 randomly selected genes from a newly assembled transcriptome. In this study, rampant gene flow was detected between species, estimated as M = 3.36 × 10(-9) to 1.20 × 10(-6) , resulting in contradicting phylogenies across loci. Nevertheless, beast analyses revealed the species identity and the effects of extrinsic cohesive forces that counteracted the non-stop introgression. As expected, early in speciation with gene flow, only 3-13 loci were highly diverged; two to five outliers (approximately 2.78-6.94% of the genome) were characterized by strong linkage disequilibrium, and asymmetrically distributed among ecotypes, indicating footprints of diversifying selection. In conclusion, ecological speciation of incipient species of Miscanthus probably followed the parapatric model, whereas allopatric speciation cannot be completely ruled out, especially between the geographically isolated northern and southern M. sinensis, for which no significant gene flow across oceanic barriers was detected. Divergence between local ecotypes in early-stage speciation began at a few genomic regions under the influence of natural selection and divergence hitchhiking that overcame gene flow.


Translational opportunities of single-cell biology in atherosclerosis.
The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.


Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1.
The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell stemness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.


Analysis of the polarization-dependent diffraction from a metallic grating by use of a three-dimensional combined vectorial method.
A three-dimensional combined vectorial method, which is based on the finite-difference time-domain algorithm and vectorial diffraction formulation, is introduced to analyze the interaction of a realistic focused beam with a metallic grating in an optical storage system. The diffracted field patterns and the detected signals are calculated for gratings with different geometries, and the polarization-dependent characteristics are studied. The combined method can give accurately the detected signals and the field pattern at any desired position of the optical storage system.


pH-Triggered self-assembly and hydrogelation of cyclic peptide nanotubes confined in water micro-droplets.
The controlled one-dimensional supramolecular polymerization of synthetic building blocks in confined spaces constitutes a key challenge to simplify the understanding of the fundamental physical principles behind the behavior of more complex encapsulated polymer networks. Cyclic peptide nanotubes constitute an optimal scaffold for the fabrication of hierarchical one-dimensional self-assembled architectures. Herein we report the pH-controlled nanotube formation and fibrillation of supramolecular cyclic peptides in confined aqueous droplets. The externally triggered self-assembly of these peptides gave rise to viscoelastic hydrogels in which the one-dimensional molecular arrangement was perfectly preserved from the nano- to the micro-scale. The cyclic peptide building blocks were confined inside water microdroplets and the base-triggered supramolecular polymerization was externally triggered and followed by confocal microscopy showing that the confined fibrillation spanned and affected the shape of the droplet micro container.


Morphological and clinical risk factors for the rupture of anterior communicating artery aneurysms.
Patients with ruptured anterior communicating artery (ACoA) aneurysms have historically been observed to have poor neuropsychological outcomes, and ACoA aneurysms have accounted for a higher proportion of ruptured than unruptured aneurysms. Authors of this study aimed to investigate the morphological and clinical characteristics predisposing to ACoA aneurysm rupture. Data from 140 consecutive patients with ACoA aneurysms managed at the authors' facility between July 2003 and November 2011 were retrospectively reviewed. Patients with (78) and without (62) aneurysm rupture were divided into groups, and morphological and clinical characteristics were compared. Morphological characteristics were evaluated based on 3D CT angiography and included aneurysm location, dominance of the A1 portion of the anterior cerebral artery, direction of the aneurysm dome around the ACoA, aneurysm bleb(s), size of the aneurysm and its neck, aneurysm-parent artery angle, and existence of other intracranial unruptured aneurysms. Patients with ruptured ACoA aneurysms were significantly younger (a higher proportion were younger than 60 years of age) than those with unruptured lesions, and a significantly smaller proportion had hypercholesterolemia. A significantly larger proportion of patients with ruptured aneurysms showed an anterior direction of the aneurysm dome around the ACoA, had a bleb(s), and/or had an aneurysm size ≥ 5 mm. Multivariate logistic regression analysis showed that an anterior direction of the aneurysm dome around the ACoA (OR 6.0, p = 0.0012), the presence of a bleb(s) (OR 22, p < 0.0001), and an aneurysm size ≥ 5 mm (OR 3.16, p = 0.035) were significantly associated with ACoA aneurysm rupture. Findings in the present study demonstrated that the anterior projection of an ACoA aneurysm may be related to rupturing. The authors would perhaps recommend treatment to patients with unruptured ACoA aneurysms that have an anterior dome projection, a bleb(s), and a size ≥ 5 mm.


Transcription, topoisomerases and recombination.
Transcription, DNA topoisomerases and genetic recombination are interrelated for several structural reasons. Transcription can affect DNA topology, resulting in effects on recombination. It can also affect the chromatin structure in which the DNA resides. Topoisomerases can affect DNA and/or chromatin structure influencing the recombination potential at a given site. Here we briefly review the extent to which homologous direct repeat recombination and site-specific recombination in eukaryotes are affected by transcription and topoisomerases. In some cases, transcription or the absence of topoisomerases have little or no effect on recombination. In others, they are important components in the recombinational process. The common denominator of any effects of transcription and topoisomerases on recombination is their shared role in altering DNA topology.


Fine-grained information extraction from German transthoracic echocardiography reports.
Information extraction techniques that get structured representations out of unstructured data make a large amount of clinically relevant information about patients accessible for semantic applications. These methods typically rely on standardized terminologies that guide this process. Many languages and clinical domains, however, lack appropriate resources and tools, as well as evaluations of their applications, especially if detailed conceptualizations of the domain are required. For instance, German transthoracic echocardiography reports have not been targeted sufficiently before, despite of their importance for clinical trials. This work therefore aimed at development and evaluation of an information extraction component with a fine-grained terminology that enables to recognize almost all relevant information stated in German transthoracic echocardiography reports at the University Hospital of Würzburg. A domain expert validated and iteratively refined an automatically inferred base terminology. The terminology was used by an ontology-driven information extraction system that outputs attribute value pairs. The final component has been mapped to the central elements of a standardized terminology, and it has been evaluated according to documents with different layouts. The final system achieved state-of-the-art precision (micro average.996) and recall (micro average.961) on 100 test documents that represent more than 90 % of all reports. In particular, principal aspects as defined in a standardized external terminology were recognized with f 1=.989 (micro average) and f 1=.963 (macro average). As a result of keyword matching and restraint concept extraction, the system obtained high precision also on unstructured or exceptionally short documents, and documents with uncommon layout. The developed terminology and the proposed information extraction system allow to extract fine-grained information from German semi-structured transthoracic echocardiography reports with very high precision and high recall on the majority of documents at the University Hospital of Würzburg. Extracted results populate a clinical data warehouse which supports clinical research.


Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.
To determine the influence of adjunctive treatment with coumadin or aspirin on recurrence rate after percutaneous transluminal coronary angioplasty (PTCA), 248 patients in whom PTCA was assessed to be a primary success were randomized to either 325 mm aspirin daily or to coumadin treatment sufficient to maintain a prothrombin time 2 to 2.5 times the control value. The follow-up protocol included stress testing and coronary angiographic examinations 3 to 6 months after PTCA. All patients were followed for at least 9 months. Of the 122 patients randomized to coumadin 44 (36%) had recurrent stenoses as opposed to 34/126 (27%) of patients on aspirin, a difference that did not reach statistical significance at the .05 level. However, patients with at least a 6 month history of angina demonstrated a significantly different response to adjunctive treatment in that 19/43 (44%) of coumadin patients as compared with 10/48 (21%) of aspirin patients had recurrent stenoses (p less than .05). Thus, coumadin was not shown to be more effective than aspirin as adjunctive treatment after PTCA, while aspirin was shown to be superior to coumadin in patients with a longer history of angina.


A Rare Case of Neurosarcoidosis Presenting as Severe Hypothermia.
BACKGROUND Sarcoidosis is a systemic disease of unclear etiology with an estimated prevalence of 10 cases per 100,000 population. Although sarcoidosis primarily affects the pulmonary system, it affects the nervous system in 5-10% of patients with the condition. CASE REPORT This article describes a case of neurosarcoidosis with the primary presenting finding of hypothermia. A 41-year-old African-American man with a past medical history significant for hypertension, asthma, and anemia, presented to the Emergency Department after being found unresponsive at home. The patient was found to have a significantly low temperature of 27.0°C on presentation. He was subsequently diagnosed with sarcoidosis by mediastinal biopsy, which revealed non-caseating granulomas with variable stages of sclerosis, consistent with long-standing sarcoidosis. In a subsequent admission, the patient presented with hyperthermia, further suggesting hypothalamic involvement as part of the neurosarcoidosis. CONCLUSIONS Neurosarcoidosis is a rare variant of sarcoidosis that has varying presentations, including headaches, seizures, ataxia, visual disturbances, loss of sensation, and other neurologic abnormalities. By presenting this case, which to our knowledge is the first to report neurosarcoidosis presenting as hypothermia, our aim is to use it as a teaching moment and for further discussion on clinical presentations and management of such patients.


Sexual assault disclosure in relation to adolescent mental health: results from the National Survey of Adolescents.
Child sexual assault is a risk factor for a wide range of emotional and behavioral problems. Little is known about mental health functioning in relation to victims' decisions to tell someone (or not) about their assault. This study used data from a nationally representative sample of 4,023 adolescents to examine the relation between sexual assault disclosure characteristics and mental health outcomes. Results indicated that youth who disclosed the assault to someone within 1 month were at reduced risk for current major depressive episode (MDE) and delinquency. No relation was found between disclosure latency and risk for posttraumatic stress disorder (PTSD) or substance use problems. Notably, disclosure to mothers was associated with significantly reduced risk for current PTSD and delinquency.


Tryptophan and serotonin metabolism after sustained tryptophan infusion.
In an attempt to elucidate the effects of sustained administration of tryptophan on serotonin synthesis and turnover in mammalian brain, mini-osmotic pumps containing tryptophan or vehicle were implanted in albino mice for 24 and 96 h. Despite the extremely low dose of tryptophan administered by these pumps (8-12 mg/kg-day) statistically significant treatment effects were apparent with both treatment durations. Plasma and brain tryptophan concentrations varied in unison, and were inversely related to the tryptophan degradative capabilities of the liver as reflected in tryptophan pyrrolase activity. After 24 h of tryptophan infusion the hepatic enzyme activity was elevated and tryptophan values were no different from controls, and after 96 h the hepatic enzyme activity was reduced and tryptophan values in treated animals were greater than controls. Serotonin was elevated in treated animals after 24 h, but not after 96 h despite the elevated tryptophan concentration at this time. The turnover of serotonin, as evidenced by 5-hydroxyindoleacetic acid concentrations, was not significantly affected by either treatment. Hepatic degradation of tryptophan thus seemed to be an important determinant of total plasma tryptophan, and brain tryptophan values paralleled plasma tryptophan. It appears that serotonin biosynthesis is regulated by factors other than tryptophan availability when the latter is chronically elevated.


Appraisal of family doctors: an evaluation study.
Appraisal has evolved to become a key component of workforce management. However, it is not clear from existing proposals for appraisal of doctors whether employers, health authorities or primary care organisations should take responsibility for appraisal processes. To evaluate the introduction of a pilot peer appraisal system in general practice and to gain insight into the reactions of appraisers and doctors. Semi-structured telephone interviews combined with participant surveys and documentary analysis. Five health authorities in Wales. General practitioners (GPs) appointed as appraisers and volunteer practitioners (doctors). Twenty-six appraisers were appointed and given training in the appraisal process, each appraising an average of eight individuals. Appraisers and appraised doctors participated in semi-structured telephone interviews and completed separate participant questionnaires. GPs willingly undertook peer appraisal in a volunteer-based pilot study where participation was recompensed. The majority of participating clinicians were positive, with appraisers reporting the most gain. Appraisers were enthusiastic, provided the process remained non-judgemental and did not threaten or burden their colleagues. Appraised doctors were less enthusiastic but the most significant perceived benefit was the opportunity to reflect on individual performance with a supportive colleague. There were, however, repeated concerns about time, confusion with revalidation and personal development plans, worries about including health and probity queries, and an opinion that the process would be entirely different if conducted with non-volunteers or by representatives of 'management'. This study illustrated three fundamental problems for appraisal systems in general practice. First, there is as yet no organisational hierarchy in general practice. Perhaps the aggregation of practices into primary care organisations will generate a hierarchy. Second, the question of who conducts appraisals then becomes pertinent; this study illustrates a professionally-led peer appraisal model. Third, the spectre of summative assessment causes problems in appraisal schemes. Typically, only mutually agreed summaries are kept for future use in appraisal systems (for example, for promotion or discipline). So the proposal to use GP annual appraisal documentation as the basis of a summative 'revalidation' exercise is at odds with orthodox personnel practice, which regards appraisal as a formative process.


Effects of Simulated Altitude on Maximal Oxygen Uptake and Inspiratory Fitness.
Aerobic exercise at altitude has shown an increase in maximal oxygen uptake. Similar effects have been replicated by way of simulated altitude training, which have influenced various advances in the field of exercise science. Elevation Training Masks© (ETM) claim to stimulate cardiorespiratory fitness improvements similar to training at altitude, however, there is little research to support this claim. The purpose of this study was to research the effect that a hypoxia-inducing mask would have on cardiorespiratory fitness and pulmonary function through the use of a high intensity interval training (HIIT) running program. Seventeen subjects were randomized into either the control group, without the mask, or experimental group, with the mask, and participated in a 6-week HIIT protocol of 4 sessions per week. Each session included a warm up, followed by intervals of running at 80% of their heart rate reserve (HRR) for 90 seconds and followed by 3 minutes of active rest at 50-60% of HRR. A total of 6 intervals were completed per session. Within subjects, there was a significant increase in predicted VO2max (F(1,17)=7.376, P<.05). However, there was no significant difference in predicted VO2max between the control and experimental groups (F(1, 17)=3.669, p= .075). Forced inspiratory vital capacity demonstrated no significant difference within subjects (F(1, 17)= .073, p > .05), or between the two groups (F(1, 17)= 3.724, p= .073). Similar to the VO2max results, forced vital capacity demonstrated a significant increase within subjects (F(1, 17)=6.201, p<.05), but there was no significant difference between the control and experimental groups (F(1,17)=3.562, p= .079). Although the between groups data was not significant, there was a greater increase in the experimental group wearing the ETM compared to the control group not wearing the mask for all 3 variables. Data suggest that HIIT training can be a viable method of improving VO2max and pulmonary function however, training masks such as the ETM may not lead to greater overall improvements.


Effect of Chlorogenic Acid Intake on Cognitive Function in the Elderly: A Pilot Study.
To evaluate the effect of chlorogenic acids (CGAs) intake on cognitive function. In this pilot study, the Cogstate and CNS Vital Signs test batteries were used to evaluate cognitive function in 8 healthy elderly men and women complaining of subjective memory loss after a 6-month intake of a test beverage containing 330 mg of CGAs just before bedtime. After a 6-month CGA intake period, significant improvement was observed in the One Back Test of the Cogstate, the Shifting Attention Test, and Finger Tapping Test as well as in the composite memory, verbal memory, complex attention, cognitive flexibility, executive function, and motor speed domains of the CNS Vital Signs test battery. A 6-month intake of CGAs may improve attentional, executive, and memory functions in the elderly with complaints of subjective memory loss.


Congenital arhinia: A rare case.
Male, 4 months Congenital arhynia Symptoms: Absence of the nose Medication: - Clinical Procedure: - Specialty: Pediatrics and Noenatology • Genetics. Congenital defects. Congenital nasal absence (arhinia) is an extremely rare malformation. Arhinia causes severe airway obstruction and poor feeding in the affected neonate. There is an association with other facial anomalies, especially defects of the eyes, ears, palate, and midline defects. A full-term boy was born via an uncomplicated vaginal delivery. The mother was 40 years old and had a normal pregnancy. The mother had 4 previous uncomplicated pregnancies. There was no history of drug use during pregnancy. Congenital arhinia is a rare defect of embryogenesis, often associated with other anomalies that significantly influence the immediate and long-term outcomes of the neonate. It is a potentially life-threatening condition and requires the presence of a highly skilled neonatal resuscitation team at the time of delivery. Parental counseling is vital and a multidisciplinary team approach is required to optimize neonatal outcome.


Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology.
Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.


Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective.
Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated. Investigation into the role of inositol pyrophosphates (PP-IPs) has provided a novel perspective on the regulation of phosphate homeostasis. Recent data suggest that metabolic and signaling interplay between PP-IPs, ATP, and inorganic polyphosphate (polyP) influences and is influenced by cellular phosphate homeostasis. Different studies have demonstrated that the SPX protein domain is a key component of proteins involved in phosphate metabolism. How PP-IPs control some aspects of phosphate homeostasis has become clearer with the recently acquired crystal structures of SPX domains. We review here recent studies on eukaryote phosphate homeostasis and provide insights into future research.


Diastereoselective nucleophilic substitution reactions of oxasilacyclopentane acetals: application of the "inside attack" model for reactions of five-membered ring oxocarbenium ions.
The additions of nucleophiles to oxocarbenium ions derived from oxasilacyclopentane acetates proceeded with high diastereoselectivity in most cases. Sterically demanding nucleophiles such as the silyl enol ether of diethyl ketone add to the face opposite the C-2 substituent. These reactions establish the syn stereochemistry about the newly formed carbon-carbon bond. Small nucleophiles such as allyltrimethylsilane do not show this same stereochemical preference: they add from the same face as the substituent in C-2-substituted oxocarbenium ions. The stereoselectivities exhibited by both small and large nucleophiles can be understood by application of the "inside attack" model for five-membered ring oxocarbenium ions developed previously for tetrahydrofuran-derived cations. This stereoelectronic model requires attack of the nucleophile from the face of the cation that provides the products in their lower energy staggered conformations. Small nucleophiles add to the "inside" of the lower energy ground-state conformer of the oxocarbenium ion. In contrast, sterically demanding nucleophiles add to the inside of the envelope conformer where approach is anti to the C-2 substituent of the oxocarbenium ion, regardless of the ground-state conformer population.


Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.
Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival. All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella-positive culture as predictors for late infection-related death. Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella-positive blood cultures were more likely to die from late infection.


Continuous-wave rotational Raman laser in H(2).
A diode-pumped, far-off-resonance cw Raman laser in H(2) with rotational Stokes emission is reported for the first time to our knowledge. The Raman laser can produce single-wavelength emission at either 830 nm (rotational Stokes) or 1180 nm (vibrational Stokes) depending on the frequency tuning of the pump laser. The mirrors for the rotational cw Raman laser are easier to produce; the laser also exhibits a wider continuous tuning range and is less sensitive to thermal effects than the previously studied vibrational Raman laser [Opt. Lett. 26, 426 (2001) and references therein].


Annual Research Review: Attention-deficit/hyperactivity disorder in girls and women: underrepresentation, longitudinal processes, and key directions.
Attention-deficit/hyperactivity disorder (ADHD) - and its underlying behavioral dimensions of inattention and hyperactivity-impulsivity - have been understudied in females. We first cover the conceptual issues of prevalence, diagnostic practices, diversity, comorbidity, and causal factors, plus forces limiting awareness of ADHD in females. After a narrative review of cross-sectional and longitudinal findings, we conclude the following. (a) Girls meet diagnostic criteria for ADHD at just under half the rates of boys, a ratio that becomes much closer to equal by adulthood. (b) Girls and women with ADHD show a predominance of inattention and associated internalizing problems; boys and men display greater levels of hyperactive-impulsive symptoms and associated externalizing problems. (c) Sex differences in ADHD symptoms and related outcomes depend heavily on the clinical versus nonreferred nature of the samples under investigation. (d) Females with ADHD experience, on average, serious impairments, with a particularly heightened risk for problems in close relationships and engagement in self-harm. (e) Clinicians may overlook symptoms and impairments in females because of less overt (but still impairing) symptom manifestations in girls and women and their frequent adoption of compensatory strategies. Our review of predictors and mediators of adult outcomes highlights (a) the potential for heterotypically continuous pathways in females with childhood ADHD and (b) developmental progressions to self-harm, intimate partner violence, unplanned pregnancy, and comorbid psychopathology. Focusing on ADHD in females is necessary to characterize causal and maintaining mechanisms with accuracy and to foster responsive interventions, as highlighted in our closing list of clinical implications and research priorities.


Relationship between the maximum velocity and sodium affinity of the erythrocyte sodium pump and its rate constant in blood.
1. Young and mature erythrocytes from 15 normal subjects were used to compare the sodium pump rate constant measured in whole blood with the more definitive sodium affinity constant and maximum velocity of the sodium pump measured in artificial media using sodium-loaded cells. 2. Similar values were obtained from both erythrocyte fractions for the sodium affinity constant and maximum velocity and also by using two different plots. The median error in the estimate of individual sodium affinity constants and maximum velocities from regression analysis was about 20% and the precision was not improved by combining the data points for the two erythrocyte fractions. 3. The rate constant in whole blood was closely related to the sodium affinity constant and maximum velocity of the sodium pump (r = 0.75), suggesting that it was a reasonable overall assessment of available sodium pump activity. 4. Differences in the rate constant between subjects were due to differences in both the maximum velocity and sodium affinity constant of the sodium pump so that the rate constant could not be used as a guide to the underlying sodium pump physiology.


Microbiology of retropharyngeal abscesses in children.
Aspiration of retropharyngeal abscesses was performed in 14 children. Cultures were taken from aspirates for aerobic and anaerobic bacteria, and all yielded bacterial growth. Anaerobes were isolated in all patients; they were the only organisms isolated in two patients (14%) and were mixed with aerobes in 12 patients (86%). There were 78 anaerobic isolates (5.6 per specimen). The predominant anaerobes were Bacteroides species, Peptostreptococcus species, and Fusobacterium species. There were 26 aerobic isolates (1.9 per specimen). The predominant aerobes were alpha- and gamma-hemolytic streptococci, Staphylococcus aureus, Haemophilus species, and group A beta-hemolytic streptococci. beta-Lactamase production was noted in 16 isolates recovered from ten patients (71%). These included all isolates of S aureus, six of 18 Bacteroides melaninogenicus group (33%), and two of three Bacteroides oralis (67%). These findings demonstrate the major role of anaerobic organisms in retropharyngeal abscesses and the presence of beta-lactamase-producing organisms in two thirds of the patients.


Clinical Characteristics and Outcomes of Patients with Ischemic and Non-Ischemic Complete Heart Block.
Third degree or complete heart block (CHB) is a medical emergency and usually requires permanent pacemaker placement. CHB can be caused by cardiac ischemia or non-ischemic conditions such as infiltrative diseases or fibrosis. The purpose of this study is to identify the baseline clinical characteristics associated with ischemic versus non-ischemic causes of complete heart block and compare their outcomes. An institutional review broad approval was granted by the Cleveland Clinic Health System. In our study, 216 patients with CHB presenting to Fairview Hospital between January 2014 and June 2016 were initially identified using the International Classification of Disease (ICD) codes at discharge. Only the patients with a new diagnosis of complete heart block (CHB) were included in the study (total N=62), which led to the exclusion of 154 patients. The patients were characterized into non-ischemic and ischemic groups based on cardiac marker elevation, electrocardiogram changes and/or cardiac catheterization findings. In all the patients, data including the following was collected: demographics such as age, gender, ethnicity and body mass index; pre-existing comorbidities such as hypertension, chronic kidney disease, diabetes mellitus, thyroid disease, previous coronary artery disease, history of cancer; use of nodal blocking agents, electrolyte abnormalities on admission, echocardiographic parameters such as ejection fraction (EF), right ventricular systolic pressure (RVSP), left ventricular end diastolic and systolic volumes (LVEDV and LVESV, respectively). The primary outcome was all-cause mortality and the secondary outcome was pacemaker placement. Categorical variables were analyzed using chi-square and continuous variables using ANOVA. Out of 62 patients (N=62), 48 had non-ischemic and 14 had ischemic CHB. The mean age was 67 years (95% CI, 60.55-74.73) in the ischemic group and 75 years (95% CI, 71.52-78.80) in the non-ischemic group, p=0.04. Patients with ischemic CHB had a lower mean EF of 49.6% (95% CI, 42.04%-57.23%) compared to 57.42% in non-ischemic CHB patients (95% CI, 53.97%-60.87%), p=0.05. History of coronary artery disease was present in 71.4% (10/14) patients with ischemic CHB compared to 37.5% (18/48) patients with non-ischemic CHB, p=0.02. There was no statistically significant difference between the two groups in terms of gender, diabetes, hypertension, thyroid dysfunction, chronic kidney disease, nodal blocking agents, electrolyte abnormalities or smoking status. For outcomes, 6/48 (12.5%) of patients with non-ischemic CHB had died compared to 3/14 (21.4%) ischemic CHB (p=0.327). Permanent pacemaker was implanted in 45/48 patients (93.75%) of the non-ischemic CHB compared to 6/14 (42.83%) in the ischemic group (p<0.001). Patients with ischemic CHB are younger, and they have a lower ejection fraction but they are less likely to get a pacemaker compared to non-ischemic CHB. Further studies with a bigger sample size are required to understand the long term mortality outcomes of patients with CHB.


Prediction of nanoparticles-cell association based on corona proteins and physicochemical properties.
Cellular association of nanoparticles (NPs) in biological fluids is affected by proteins adsorbed onto the NP surface, forming a "protein corona", thereby impacting cellular bioactivity. Here we investigate, based on an extensive gold NPs protein corona dataset, the relationships between NP-cell association and protein corona fingerprints (PCFs) as well as NP physicochemical properties. Accordingly, quantitative structure-activity relationships (QSARs) were developed based on both linear and non-linear support vector regression (SVR) models making use of a sequential forward floating selection of descriptors. The SVR model with only 6 serum proteins and zeta potential had higher accuracy (R(2) = 0.895) relative to the linear model (R(2) = 0.850) with 11 PCFs. Considering the initial pool of 148 descriptors, the APOB, A1AT, ANT3, and PLMN serum proteins along with NP zeta potential were identified as most significant to correlating NP-cell association. The present study suggests that QSARs exploration of NP-cell association data, considering the role of both NP protein corona and physicochemical properties, can support the planning and interpretation of toxicity studies and guide the design of NPs for biomedical applications.


Enhancing images of facial expressions.
Facial images can be enhanced by application of an algorithm--the caricature algorithm--that systematically manipulates their distinctiveness (Benson & Perrett, 1991c; Brennan, 1985). In this study, we first produced a composite facial image from natural images of the six facial expressions of fear, sadness, surprise, happiness, disgust, and anger shown on a number of different individual faces (Ekman & Friesen, 1975). We then caricatured the composite images with respect to a neutral (resting) expression. Experiment 1 showed that rated strength of the target expression was directly related to the degree of enhancement for all the expressions. Experiment 2, which used a free rating procedure, found that, although caricature enhanced the strength of the target expression (more extreme ratings), it did not necessarily enhance its purity, inasmuch as the attributes of nontarget expressions were also enhanced. Naming of prototypes, of original exemplar images, and of caricatures was explored in Experiment 3 and followed the pattern suggested by the free rating conditions of Experiment 2, with no overall naming advantage to caricatures under these conditions. Overall, the experiments suggested that computational methods of compositing and caricature can be usefully applied to facial images of expression. Their utility in enhancing the distinctiveness of the expression depends on the purity of expression in the source image.


Relationship between assemblages of mycorrhizal fungi and bacteria on grass roots.
Soils support an enormous microbial diversity, but the ecological drivers of this diversity are poorly understood. Interactions between the roots of individual grass species and the arbuscular mycorrhizal (AM) fungi and bacteria in their rhizoplane were studied in a grazed, unimproved upland pasture. Individual root fragments were isolated from soil cores, DNA extracted and used to identify plant species and assess rhizoplane bacterial and AM fungal assemblages, by amplifying part of the small-subunit ribosomal RNA gene, followed by terminal restriction fragment length polymorphism analysis. For the first time we showed that AM fungal and bacterial assemblages are related in situ and that this relationship occurred at the community level. Principal coordinate analyses of the data show that the AM fungi were a major factor determining the bacterial assemblage on grass roots. We also report a strong influence of the composition of the plant community on AM fungal assemblage. The bacterial assemblage was also influenced by soil pH and was spatially structured, whereas AM fungi were influenced neither by the bacteria nor by soil pH. Our study shows that linkages between plant roots and their microbial communities exist in a complex web of interactions that act at individual and at community levels, with AM fungi influencing the bacterial assemblage, but not the other way round.


High prevalence of Strongyloides stercoralis among farm workers on the Mediterranean coast of Spain: analysis of the predictive factors of infection in developed countries.
Strongyloidiasis is a parasitosis characterized by persistent infection before dissemination and the development of potentially fatal disease. Since diagnosis is difficult, knowledge of the prevalence and geographic distribution of the disease is of practical importance. A study was made of Strongyloides stercoralis infection in a random and representative sample of farm workers in a tourist region in Spain based on the detection of larvae of triple stool samples. The prevalence of infection was 12.4% (95% confidence interval [CI] = 8.4-16.4). None of the 26 clinical or epidemiologic variables analyzed were found to be predictive of infection. Only eosinophilia (> 400 eosinophils/mm3) was significantly greater among the infected individuals (odds ratio = 73.4, 95% CI = 16.3-327.0), with a sensitivity of 93.5% and a specificity of 93.1%. A screening program is proposed to detect eosinophilia, to provide treatment without stool examinations, and thus afford a cost-effective policy for preventing the development of severe forms of the disease among specific risk groups where the prevalence of other parasitoses is low.


Protective Lung Ventilation and Morbidity After Pulmonary Resection: A Propensity Score-Matched Analysis.
Protective lung ventilation (PLV) during one-lung ventilation (OLV) for thoracic surgery is frequently recommended to reduce pulmonary complications. However, limited outcome data exist on whether PLV use during OLV is associated with less clinically relevant pulmonary morbidity after lung resection. Intraoperative data were prospectively collected in 1080 patients undergoing pulmonary resection with OLV, intentional crystalloid restriction, and mechanical ventilation to maintain inspiratory peak airway pressure <30 cm H2O. Other ventilator settings and all aspects of anesthetic management were at the discretion of the anesthesia care team. We defined PLV and non-PLV as <8 or ≥8 mL/kg (predicted body weight) mean tidal volume. The primary outcome was the occurrence of pneumonia and/or acute respiratory distress syndrome (ARDS). Propensity score matching was used to generate PLV and non-PLV groups with comparable characteristics. Associations between outcomes and PLV status were analyzed by exact logistic regression, with matching as cluster in the anatomic and nonanatomic lung resection cohorts. In the propensity score-matched analysis, the incidence of pneumonia and/or ARDS among patients who had an anatomic lung resection was 9/172 (5.2%) in the non-PLV compared to the PLV group 7/172 (4.1%; odds ratio, 1.29; 95% confidence interval, 0.48-3.45, P= .62). The incidence of pneumonia and/or ARDS in patients who underwent nonanatomic resection was 3/118 (2.5%) in the non-PLV compared to the PLV group, 1/118 (0.9%; odds ratio, 3.00; 95% confidence interval, 0.31-28.84, P= .34). In this prospective observational study, we found no differences in the incidence of pneumonia and/or ARDS between patients undergoing lung resection with tidal volumes <8 or ≥8 mL/kg. Our data suggest that when fluid restriction and peak airway pressures are limited, the clinical impact of PLV in this patient population is small. Future randomized trials are needed to better understand the benefits of a small tidal volume strategy during OLV on clinically important outcomes.


Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.
To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. 39 NNUs from 12 countries. Any neonate admitted to one of the participating NNUs. This was an observational cohort study. The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.


Implications of nonrandom seed abscission and global stilling for migration of wind-dispersed plant species.
Migration of plant populations is a potential survival response to climate change that depends critically on seed dispersal. Biological and physical factors determine dispersal and migration of wind-dispersed species. Recent field and wind tunnel studies demonstrate biological adaptations that bias seed release toward conditions of higher wind velocity, promoting longer dispersal distances and faster migration. However, another suite of international studies also recently highlighted a global decrease in near-surface wind speeds, or 'global stilling'. This study assessed the implications of both factors on potential plant population migration rates, using a mechanistic modeling framework. Nonrandom abscission was investigated using models of three seed release mechanisms: (i) a simple drag model; (ii) a seed deflection model; and (iii) a 'wear and tear' model. The models generated a single functional relationship between the frequency of seed release and statistics of the near-surface wind environment, independent of the abscission mechanism. An Inertial-Particle, Coupled Eulerian-Lagrangian Closure model (IP-CELC) was used to investigate abscission effects on seed dispersal kernels and plant population migration rates under contemporary and potential future wind conditions (based on reported global stilling trends). The results confirm that nonrandom seed abscission increased dispersal distances, particularly for light seeds. The increases were mitigated by two physical feedbacks: (i) although nonrandom abscission increased the initial acceleration of seeds from rest, the sensitivity of the seed dispersal to this initial condition declined as the wind speed increased; and (ii) while nonrandom abscission increased the mean dispersal length, it reduced the kurtosis of seasonal dispersal kernels, and thus the chance of long-distance dispersal. Wind stilling greatly reduced the modeled migration rates under biased seed release conditions. Thus, species that require high wind velocities for seed abscission could experience threshold-like reductions in dispersal and migration potential if near-surface wind speeds continue to decline.


Effect of Pet Insects on the Psychological Health of Community-Dwelling Elderly People: A Single-Blinded, Randomized, Controlled Trial.
There is evidence that animal-assisted therapy has positive effects on mental health, especially in elderly people. Caring for insects is easy, relatively inexpensive, and does not require much space. The aim of this 8-week randomized, controlled, single-blinded study was to investigate the effect of pet insects on the psychological health of community-dwelling elderly people. Elderly subjects (≥65 years old) attending a community center in Daegu, Korea, were enrolled in the study between April and May 2014 and randomized at a 1:1 ratio to receive insect therapy and health advice or only health advice. The insect group received 5 crickets in a cage with sufficient fodder and a detailed instruction manual. At baseline and at 8 weeks, all subjects underwent psychometric tests via a direct interview [Beck Anxiety Inventory, Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), 36-Item Short Form Health Survey, Insomnia Severity Index, Fatigue Severity Scale, and Brief Encounter Psychosocial Instrument] and laboratory analyses of inflammatory and oxidative stress markers (erythrocyte sedimentation rate, high-sensitivity C-reactive protein, biological antioxidant potential, and derivatives of reactive oxygen metabolites). The insect-caring (n = 46) and control (n = 48) groups did not differ in baseline characteristics. The insect-caring group had significantly lower GDS-15 scores at week 8 (3.20 vs. 4.90, p = 0.004) and, after adjustment for baseline values, a significantly greater change in GDS-15 scores relative to baseline (-1.12 vs. 0.20, p = 0.011). They also had a significantly greater change in MMSE scores relative to baseline (1.13 vs. 0.31, p = 0.045). The two groups did not differ in terms of other psychometric and laboratory tests. No serious risks or adverse events were reported. Caring for insects, which is cost-effective and safe, was associated with a small to medium positive effect on depression and cognitive function in community-dwelling elderly people.


Dispersal of adult culex mosquitoes in an urban west nile virus hotspot: a mark-capture study incorporating stable isotope enrichment of natural larval habitats.
Dispersal is a critical life history behavior for mosquitoes and is important for the spread of mosquito-borne disease. We implemented the first stable isotope mark-capture study to measure mosquito dispersal, focusing on Culex pipiens in southwest suburban Chicago, Illinois, a hotspot of West Nile virus (WNV) transmission. We enriched nine catch basins in 2010 and 2011 with 15N-potassium nitrate and detected dispersal of enriched adult females emerging from these catch basins using CDC light and gravid traps to distances as far as 3 km. We detected 12 isotopically enriched pools of mosquitoes out of 2,442 tested during the two years and calculated a mean dispersal distance of 1.15 km and maximum flight range of 2.48 km. According to a logistic distribution function, 90% of the female Culex mosquitoes stayed within 3 km of their larval habitat, which corresponds with the distance-limited genetic variation of WNV observed in this study region. This study provides new insights on the dispersal of the most important vector of WNV in the eastern United States and demonstrates the utility of stable isotope enrichment for studying the biology of mosquitoes in other disease systems.


Interdisciplinary staffing patterns: do for-profit and nonprofit hospices differ?
Interdisciplinary care is fundamental to the hospice philosophy and is a key component of high-quality hospice care. However, little is known about how hospices differ in their interdisciplinary staffing patterns, particularly across nonprofit and for-profit hospices. The purpose of this study was to examine potential differences in the staffing patterns of for-profit and nonprofit hospices. Using the 2006 Medicare Provider of Services (POS) survey, we conducted a cross-sectional analysis of staffing patterns within Medicare-certified hospices operating in the United States in 2006. In bivariate and multivariable analyses, we examined differences in staffing patterns measured by the existence of a full range of interdisciplinary staff (defined as having at least 1 full-time equivalent (FTE) staff in each of 4 disciplines ascertained by the survey: physician, nursing, psychosocial, and home health aide) and by the professional mix of staff within each discipline. For-profit hospices had a winder range of paid staff but there were no differences by ownerships when volunteer staff were included. For-profit hospices had significantly fewer registered nurse FTEs as a proportion of nursing staff, fewer medical social worker FTEs as a proportion of psychosocial staff, and fewer clinician FTEs as a proportion of total staff (p values <0.05). Compared to nonprofit hospices, for-profit and government-owned hospices also used proportionally fewer volunteer FTEs. Hospice staffing patterns differed significantly by ownership type. Future research should evaluate the impact of these differences on quality of care and satisfaction among patients and families using hospice.


Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor.
The spiroindolones, a new class of antimalarial medicines discovered in a cellular screen, are rendered less active by mutations in a parasite P-type ATPase, PfATP4. We show here that S. cerevisiae also acquires mutations in a gene encoding a P-type ATPase (ScPMA1) after exposure to spiroindolones and that these mutations are sufficient for resistance. KAE609 resistance mutations in ScPMA1 do not confer resistance to unrelated antimicrobials, but do confer cross sensitivity to the alkyl-lysophospholipid edelfosine, which is known to displace ScPma1p from the plasma membrane. Using an in vitro cell-free assay, we demonstrate that KAE609 directly inhibits ScPma1p ATPase activity. KAE609 also increases cytoplasmic hydrogen ion concentrations in yeast cells. Computer docking into a ScPma1p homology model identifies a binding mode that supports genetic resistance determinants and in vitro experimental structure-activity relationships in both P. falciparum and S. cerevisiae. This model also suggests a shared binding site with the dihydroisoquinolones antimalarials. Our data support a model in which KAE609 exerts its antimalarial activity by directly interfering with P-type ATPase activity.


Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study.
Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's κ. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Of the 706 patients, 301 (42.6%) met both definitions. The inter-rater agreement (κ ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69% (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis.


Prevalence of MDR organism (MDRO) carriage in children and their household members in Siem Reap Province, Cambodia.
The rising incidence of infections caused by MDR organisms (MDROs) poses a significant public health threat. However, little has been reported regarding community MDRO carriage in low- and middle-income countries. We conducted a cross-sectional study in Siem Reap, Cambodia comparing hospital-associated households, in which an index child (age: 2-14 years) had been hospitalized for at least 48 h in the preceding 2-4 weeks, with matched community households on the same street, in which no other child had a recent history of hospitalization. Participants were interviewed using a survey questionnaire and tested for carriage of MRSA, ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) by culture followed by antibiotic susceptibility testing. We used logistic regression analysis to analyse associations between collected variables and MDRO carriage. Forty-two pairs of households including 376 participants with 376 nasal swabs and 290 stool specimens were included in final analysis. MRSA was isolated from 26 specimens (6.9%). ESBL-producing Escherichia coli was detected in 269 specimens (92.8%) whereas ESBL-producing Klebsiella pneumoniae was isolated from 128 specimens (44.1%), of which 123 (42.4%) were co-colonized with ESBL-producing E. coli. Six (2.1%) specimens tested positive for CPE (4 E. coli and 2 K. pneumoniae). The prevalence ratios for MRSA, ESBL-producing E. coli and ESBL-producing K. pneumoniae carriage did not differ significantly in hospital-associated households and hospitalized children compared with their counterparts. The high prevalence of ESBL-E across both household types suggests that MDRO reservoirs are common in the community. Ongoing genomic analyses will help to understand the epidemiology and course of MDRO spread.


Polarizable Drude Model with s-Type Gaussian or Slater Charge Density for General Molecular Mechanics Force Fields.
Gas-phase electric properties of molecules can be computed routinely using wave function methods or density functional theory (DFT). However, these methods remain computationally expensive for high-throughput screening of the vast chemical space of virtual compounds. Therefore, empirical force fields are a more practical choice in many cases, particularly since force field methods allow one to routinely predict the physicochemical properties in the condensed phases. This work presents Drude polarizable models, to increase the physical realism in empirical force fields, where the core particle is treated as a point charge and the Drude particle is treated either as a 1 s-Gaussian or a ns-Slater ( n = 1, 2, 3) charge density. Systematic parametrization to large high-quality quantum chemistry data obtained from the open access Alexandria Library ( https://doi.org/10.5281/zenodo.1004711 ) ensures the transferability of these parameters. The dipole moments and isotropic polarizabilities of the isolated molecules predicted by the proposed Drude models are in agreement with experiment with accuracy similar to DFT calculations at the B3LYP/aug-cc-pVTZ level of theory. The results show that the inclusion of explicit polarization into the models reduces the root-mean-square deviation with respect to DFT calculations of the predicted dipole moments of 152 dimers and clusters by more than 50%. Finally, we show that the accuracy of the electrostatic interaction energy of the water dimers can be improved systematically by the introduction of polarizable smeared charges as a model for charge penetration.


Analysis of Cutaneous Adverse Drug Reactions Reported at the Regional ADR Monitoring Center.
Skin is one of the major target organ for adverse drug reactions (ADRs). The incidence of dermatological ADRs among indoor patients in developed countries ranges from 1-3%, whereas in developing countries such as India, it is 2-5%. To analyze the clinical spectrum, seriousness, outcome, causality, severity, and preventability of the cutaneous ADRs. All cutaneous ADRs reported at the Regional Adverse Drug Reaction Monitoring Center between January 2013 to May 2016 were identified and evaluated. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and the Naranjo'a reactions (ADRs) Severity (Hartwig and Seigel scale), and preventability (Schumock and Thornton criteria) of a said drug. Out of 2171 ADRs reported during study period, 538 were cutaneous ADRs (24.78%). The most common clinical presentation was maculopapular rash (58.92%) followed by itching (10.59%), and Stevens-Johnson syndrome (4.83%). The time relationship of cutaneous ADRs to drug therapy revealed that they can develop within 1 week to 1 year of treatment. Most common causal drug groups were antimicrobials (46%), non-steroidal anti-inflammatory drugs (NSAIDs) (18%), and antiepileptics (10%). Polypharmacy was observed in 7% of the cases. Most of the cutaneous ADRs were non-serious (91%), however, 10 were life-threatening and 1 was resulted in death due to the Stevens-Johnson syndrome. Causality category for majority of cutaneous ADRs was possible. Although majority of cutaneous ADRs were moderately severe (81%), however, not preventable (89%). The occurrence of cutaneous ADRs is common and they developed within 1 week of therapy. Antimicrobial agents and NSAIDs are the most common implicated drug class. Hence, physicians should closely monitor the patient in the first week while using such therapy for early detection and prevention of cutaneous ADRs.


Portal hypertension in children and young adults with biliary atresia.
Biliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA. Subjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite" when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible" if one of the findings was present in the absence of a complication, whereas PHT was "absent" if none of the criteria were met. A total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, γ-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin <3 g/dL. Clinically definable PHT is present in two-thirds of North American long-term BA survivors with their native livers. The presence of PHT is associated with measures of hepatic injury and dysfunction, although in this selected cohort, the degree of hepatic dysfunction is relatively mild and growth is preserved.


Vitamin C infusion treatment enhances cortisol production of the adrenal via the pituitary ACTH route.
The present study is an extension of our past study on the clinical use of vitamin C infusion or injection treatment in autoimmune disease and allergy which suggests that the intravenous introduction of vitamin C may enhance the activity of the endogenous cortisol in such a way as to allow clinical control of immune disorders. This time, we investigated the relation between ACTH, cortisol and vitamin C in plasma in the course of vitamin C infusion or injection treatment with and without the use of methyl-prednisolone annex, a suppressor of the homeostatic mechanism of the pituitary ACTH. A total of 4 experiments were conducted using a healthy male volunteer. Results obtained are as follows: 1) the practice of the steroid-free vitamin C infusion treatment induced a) distinct depletion of both cortisol and vitamin C from the circulation at the initial to moderate stages of the experiment, b) a small surge of plasma cortisol at the middle stage, and c) skyrocket-like rises of ACTH and cortisol of plasma at the terminal stage. 2) The use of methylprednisolone annex in the vitamin C infusion set completely suppressed the emergence of the plasma ACTH/cortisol surges of the terminal stage, but not the small surge of plasma cortisol. The synthetic steroid also suppressed the depletion of vitamin C and cortisol of the initial to moderate stages. 3) The terminal ACTH/cortisol surges of plasma were less distinct in the vitamin C infection experiment than in the vitamin C infusion experiment.(ABSTRACT TRUNCATED AT 250 WORDS)


Protective Effect of Contralateral, Ipsilateral, and Bilateral Remote Ischemic Preconditioning on Spinal Cord Ischemia Reperfusion Injury in Rats.
To evaluate the effect of different remote ischemic preconditioning (RIPC) methods in spinal cord ischemia-reperfusion (IR) injury. A total of 36 rats were distributed to the 6 groups: sham surgery, control (only spinal cord IR), unilateral (hind limb RIPC before spinal cord IR), bilateral (hind limbs RIPC before spinal cord IR), ipsilateral (hind and fore limbs RIPC to the right before spinal cord IR), contralateral (right hind limb and left fore limb as RIPC before spinal cord IR). Thirty minutes after RIPC, the spinal cord was subjected to ischemia for 60 minutes. Seventy two hours after IR, all rats were evaluated by neurological function, histological and biochemical examinations. The mean Motor Deficit Index (MDI) scores in the ipsilateral, contralateral, and bilateral groups were lower than that of the unilateral group (p < 0.05). The mean malondialdehyde (MDA) in ipsilateral group was lower than were control group (p < 0.05). The mean total antioxidant capacity (TAC) and the mean number of normal motor neurons in the experimental groups were significantly higher than increased control group (p < 0.05). The mean plasma levels of catalase in the contralateral, ipsilateral, and bilateral groups were significantly increased compared to control group (p < 0.05). The mean scores of white matter damage in contralateral, bilateral, and unilateral groups were lower than control group (p < 0.05). The results of this study show that contralateral, ipsilateral, and bilateral limb RIPC may reduce the complications of spinal cord ischemic injury.


A Concise Total Synthesis of (-)-Mesembrine.
A concise total synthesis of mesembrine (four steps from known compound) was achieved both racemically and asymmetrically. Two key reactions were used here. One is the Rh(I)-catalyzed [5 + 1] cycloaddition of vinylcyclopropane 3c and CO. The other one is Buchwald's Pd-catalyzed coupling reaction that coupled β,γ-cyclohexenone 2c with aryl bromide 5 (using dppe ligand for racemic or (S)-Antphos ligand for asymmetric synthesis) to give γ,γ-disubstituted α,β-cyclohexenone 1c. Finally, aza-Michael addition converted 1c to mesembrine.


Induced Polarization in Molecular Dynamics Simulations of the 5-HT3 Receptor Channel.
Ion channel proteins form water-filled nanoscale pores within lipid bilayers, and their properties are dependent on the complex behavior of water in a nanoconfined environment. Using a simplified model of the pore of the 5-HT3 receptor (5HT3R) which restrains the backbone structure to that of the parent channel protein from which it is derived, we compare additive with polarizable models in describing the behavior of water in nanopores. Molecular dynamics simulations were performed with four conformations of the channel: two closed state structures, an intermediate state, and an open state, each embedded in a phosphatidylcholine bilayer. Water density profiles revealed that for all water models, the closed and intermediate states exhibited strong dewetting within the central hydrophobic gate region of the pore. However, the open state conformation exhibited varying degrees of hydration, ranging from partial wetting for the TIP4P/2005 water model to complete wetting for the polarizable AMOEBA14 model. Water dipole moments calculated using polarizable force fields also revealed that water molecules remaining within dewetted sections of the pore resemble gas phase water. Free energy profiles for Na+ and for Cl- ions within the open state pore revealed more rugged energy landscapes using polarizable force fields, and the hydration number profiles of these ions were also sensitive to induced polarization resulting in a substantive reduction of the number of waters within the first hydration shell of Cl- while it permeates the pore. These results demonstrate that induced polarization can influence the complex behavior of water and ions within nanoscale pores and provides important new insights into their chemical properties.


Improving the participation of youth with physical disabilities in community activities: An interrupted time series design.
Youth with physical disabilities experience restrictions to participation in community-based leisure activities; however, there is little evidence about how to improve their involvement. This study examined whether an intervention to remove environmental barriers and develop strategies using a coaching approach improved youth participation in leisure activities. An Interrupted Time Series design was employed, where replication of the intervention effect was examined across individualised participation goals and across participants. Six adolescents with a physical disability participated in a 12-week intervention. An occupational therapist worked with each youth and his/her family to set three leisure goals based on problems identified using the Canadian Occupational Performance Measure (COPM). A coaching approach was used to collaboratively identify and implement strategies to remove environmental barriers. Interventions for each goal were introduced at different time points. Outcomes were evaluated using the COPM. Improvements in COPM performance scores were clinically significant for 83% of the identified activities; an average change of 4.5 points in the performance scale (SD = 1.95) was observed. Statistical analysis using the celeration line demonstrated that the proportion of data points falling above the line increased in the intervention phase for 94% of the activities, indicating a significant treatment effect. This study is the first to examine an intervention aimed at increasing leisure participation by changing only the environment. The results indicate that environment-focussed interventions are feasible and effective in promoting youth participation. Such findings can inform the design of a larger study and guide occupational therapy practice.


Self-management Needs of Adults With Congenital Heart Disease.
Adults with congenital heart disease (CHD) are an emerging adult heart disease subset, now outnumbering the pediatric population with CHD. We aimed to gain understanding and knowledge of what adults with CHD perceive as important for self-management and describe these needs across demographic factors, developmental characteristics, lesion severity, and quality of life. We used a descriptive mixed-methods online survey merging 4 instruments: Adult CHD Self-management Experience Questionnaire; Adult CHD Demographic Questionnaire; Adaptive Behavior Assessment System, Third Edition; and Stanford Quality of Life Visual Numeric. Participants with CHD 18 to 30 years of age with initial defect repair before 12 months of age were recruited through support from the Adult Congenital Heart Association, clinic adult CHD support groups, and newspaper advertising. Thematic analysis for short-answer questions, descriptive analysis for demographic data and the visual numeric, and intrument-specific scoring assistant software for the Adaptive Behavior Assessment System were used. We received 22 responses from 13 women and 9 men. These individuals represented 15 different heart defect diagnoses, mostly of moderate or complex lesion severity. Most had postsecondary education and were employed. Four prominent themes emerged related to self-management: desire for connectivity-psychological support; a plan for the future-education about health and life expectations; coping needs-skills for mental stress; and access to care-navigation of healthcare systems. Future longitudinal research and replication studies with larger samples are needed. Educational materials and targeted interventions that promote self-management benefit the aging adult with CHD population.


Using item response theory (IRT) to improve the efficiency of the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis.
The SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of individual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. The original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. SCCAI data for 516 UC patients (41 years, SD = 15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items < 1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day; bowel frequency nocturnal; urgency to defaecation; rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom) or non-endorsement of the trait (disease activity). Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.


Rape shield laws and sexual behavior evidence: effects of consent level and women's sexual history on rape allegations.
Rape shield laws, which limit the introduction of sexual history evidence in rape trials, challenge the view that women with extensive sexual histories more frequently fabricate charges of rape than other women. The present study examined the relationship between women's actual sexual history and their reporting rape in hypothetical scenarios. Female participants (college students and a community sample, which included women working as prostitutes and topless dancers, and women living in a drug and alcohol rehabilitation center) imagined themselves in dating scenarios that described either a legally definable act of rape or consensual sexual intercourse. Additionally, within the rape scenarios, level of consensual intimate contact (i.e., foreplay) preceding rape was examined to determine its influence on rape reporting. Women were less likely to say that they would take legal action in response to the rape scenarios if they had extensive sexual histories, or if they had consented to an extensive amount of intimate contact before the rape. In response to the consensual sexual intercourse scenarios, women with more extensive sexual histories were not more likely to say that they would report rape, even when the scenario provided them with a motive for seeking revenge against their dating partner.


Experimental demonstration of microring-based optical pulse train generator.
Recently, we proposed the concept of a microring-based optical pulse train generator, which uses a series of microrings coupled to a waveguide and time-interleaves a trigger pulse propagating on this waveguide to generate an optical pulse train. When each ring is electrically modulated, this electronic-photonic integrated circuit (EPIC) can be used for optical arbitrary waveform generation (OAWG) and ultrafast electro-optic (EO) modulation. This paper presents the proof-of-concept experimental demonstration of this technique with two four-stage chip prototypes fabricated on silicon-on-insulator (SOI) substrate. Device fabrication and testing of the chip prototypes are presented. The measurement results show that from a 20-ps-wide input trigger pulse, two circuits generate four sequential pulses at the output with a constant stage delay of 55 ps and 30 ps respectively, which translate into pulse repetition rates of 18 GHz and 33 GHz.


Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm forms.
Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals. Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants. A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins. Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues. Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi.


Examining microcirculation improves the angiosome theory in explaining the delay phenomenon in a rabbit model.
Topographic and temporal changes in circulation were studied with laser Doppler flowmetry in rabbit dorsal skin flaps comprised of three vascular territories. The reduced caliber vessels along the dorsal median line, rather than the vessels interconnecting the thoracodorsal and deep circumflex iliac vascular trees, behaved as true choke vessels. The authors found an increased proximal circulation lasting for 48 to 72 hr. This coincided with the reported rapid phase of choke vessel dilatation. The increase in distal circulation began after postoperative day 3, coinciding with the resolution of proximal hyperemia but not with the earlier prominent vasodilatation. Secondary elevation of the flaps at 3 weeks did not disturb the homogeneous distribution of circulation and did not cause a hyperemic response at postoperative 24 hr. Based on these findings, the authors postulate that the same mechanisms may underlie the rapid choke vessel dilatation and microvascular dilatation observed at 48 to 72 hr postoperatively. Surgical delay may work not only by diminishing the resistance to blood flow along the flap, but also by diminishing the steal effect of increased proximal microcirculation, which characterizes this period, over the distal circulation.


The Co-creation and Feasibility of a Compassion Training as a Follow-up to Mindfulness-Based Cognitive Therapy in Patients with Recurrent Depression.
The aim of this study was to assess the feasibility, acceptability and preliminary effectiveness of Mindfulness - Based Compassionate Living (MBCL) as a follow-up intervention to Mindfulness Based Cognitive Therapy in adults with recurrent depression. We conducted an uncontrolled study in 17 patients with recurrent depression, in two successive groups. The first group contained novices to compassion training (N = 14); in the second group, ten of these participated again, in addition to three new participants (N = 13). The overall group contained 15 females and 2 males, aged between 37 and 71. The MBCL program was qualitatively evaluated using post-intervention focus group interviews in both groups. In addition, self-report questionnaires assessing depressive symptoms, worry and both self-compassion and mindfulness skills were administered before and after MBCL. No patients dropped out of the intervention. Average attendance was 7.52 (SD 0.73) out of eight sessions. Helpful elements were theory on the emotion regulation systems, practicing self-compassion explicitly and embodiment of a compassionate attitude by the teachers. Unhelpful elements were the lack of a clear structure, lack of time to practice compassion for self and the occurrence of the so-called back draft effect. We adapted the program in accordance with the feedback of the participants. Preliminary results showed a reduction in depressive symptoms in the second group, but not in the first group, and an increase in self-compassion in both groups. Worry and overall mindfulness did not change. MBCL appears to be feasible and acceptable for patients suffering from recurrent depressive symptoms who previously participated in MBCT. Selection bias may have been a factor as only experienced and motivated participants were used; this, however, suited our intention to co-create MBCL in close collaboration with knowledgeable users. Examination of the effectiveness of MBCL in a sufficiently powered randomised controlled trial is needed.


Incidence of radiographic unicompartmental arthritis in patients undergoing knee arthroplasty.
Unicompartmental knee arthroplasty is increasing in popularity with the advent of less invasive procedures for knee arthritis. The percentage of patients undergoing knee arthroplasty who could be candidates for unicompartmental knee arthroplasty depends on the surgeon's evaluation of the radiographs, and this evaluation may depend on the surgeon's bias regarding partial knee arthroplasty. A retrospective radiographic and chart review was performed on a consecutive series of patients who had undergone tricompartmental knee arthroplasty to determine the percentage of those patients who could have been candidates for unicompartmental knee arthroplasty. Two hundred eighty-eight patients who underwent 308 tricompartmental knee arthroplasties over a 3-year period at a Veteran's Administration Hospital comprised the study group. Assessment of preoperative radiographs was done by 2 surgeons, 1 who favored unicompartmental knee arthroplasty and the other who preferred tricompartmental knee arthroplasty, to determine the percentage of these patients, from each surgeon's viewpoint, who had unicompartmental arthritis. Patients who had radiographic unicompartmental arthritis were then eliminated as candidates for unicompartmental knee arthroplasty, if, on chart review, they had a flexion contracture >10°, an arc of motion <100°, or inflammatory arthritis. The surgeon who was a proponent of unicompartmental knee arthroplasty found that 26% of these patients had acceptable radiologic and clinical indications for unicompartmental knee arthroplasty, whereas the surgeon who had a bias against the procedure felt that only 12% of these patients were unicompartmental knee arthroplasty candidates. A considerable percentage of Veteran's Administration patients undergoing arthroplasty for knee arthritis may be potential candidates for unicompartmental knee arthroplasty, despite the surgeon's bias for or against the procedure.


Biaxial and uniaxial phases produced by partly repulsive mesogenic models involving D2h molecular symmetries.
The present paper considers biaxial nematogenic lattice models, involving particles of D2h symmetry, whose centers of mass are associated with a three-dimensional simple-cubic lattice. The pair potential is isotropic in orientation space and restricted to nearest neighbors. Let two orthonormal triads define orientations of a pair of interacting particles. The investigated potential models are quadratic with respect to the nine scalar products between the two sets of unit vectors. Actually, based on available geometric identities, these expressions can be reduced to diagonal form containing only the scalar products between corresponding unit vectors and depending on three parameters. Over the years, this comparatively simple functional form has also proven to be rather versatile. By now, various sets of potential parameters capable of producing mesogenic behavior of some kind have been proposed and studied in the literature. A new and simplified form was recently proposed and investigated by Sonnet, Virga, Durand, and De Matteis [A. M. Sonnet, E. G. Virga, and G. E. Durand, Phys. Rev. E 67, 061701 (2003); G. De Matteis and E. G. Virga, Phys. Rev. E 71, 061703 (2005)] and is known to support a biaxial phase at sufficiently low temperature. Following the idea of the above authors, we have studied a more extended range of parameters, including cases where biaxiality cannot be sustained in the pair ground state. In cases where a biaxial phase survives, an appropriate mean-field analysis may predict the existence of a direct second-order transition to the isotropic phase as well as a second-order sequence isotropic-to-uniaxial-to-biaxial. A second-order phase transition is also predicted, which involves isotropic and uniaxial phases only. Monte Carlo simulations have been carried out as well, for a few points in the parameter space, and found to produce results which partly confirm mean-field predictions.


Liquid Ice fails to cool the skin surface as effectively as crushed ice in a wet towel.
One sought to compare surface cooling produced by two cryotherapy modalities (crushed ice in a room temperature wet towel and Liquid Ice). Twenty-five university students (10 female and 15 male) between 19 and 29 years of age (mean+/-SD: 21.36+/-2.33) participated in this study. Skin surface temperature was measured prior to, immediately after 20-minute application, and 20-minute postapplication of the cryotherapy modality using an infrared camera. Both cryotherapy modalities decreased the baseline skin surface temperature (crushed ice: 28.6+/-1.3 to 6.8+/-1.8 degrees C; Liquid Ice: 28.6+/-1.6 to 25.2+/-1.56 degrees C; p<0.001). Similarly, at 20 minutes postapplication of both cryotherapy modalities the skin surface temperature remained significantly inferior to baseline (crushed ice: 21.8+/-1.0 degrees C; Liquid Ice: 27.4+/-1.6 degrees C; p<0.001). The magnitude of the decrease was greater after the application of crushed ice in a room temperature wet towel than Liquid Ice, both immediately after application (temperature fall: 21.8+/-1.6 degrees C versus 3.4+/-0.7 degrees C; p<0.001) and 20 minutes postapplication (temperature fall: 6.8+/-0.8 degrees C versus 1.2+/-0.6 degrees C; p<0.001). Assuming that greater cooling seems to be better, the present results suggest that: 1) a 20-minute application of crushed ice in a room temperature wet towel is more effective at cooling skin temperature than evaporative cooling menthol-based products and 2) Liquid Ice(TM) is not a clinically useful modality.


Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.
Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.


Ostomy Care at Home.
: This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.The articles in this new installment of the series provide simple and useful instructions that nurses should reinforce with family caregivers who perform wound care tasks. Each article also includes an informational tear sheet-Information for Family Caregivers-that contains links to instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses.


Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients.
Penicilloyl groups, which have been connected to penicillin allergy, are derived from penicillin by cleavage of the beta lactam ring and bind covalently to proteins. Fixation of penicilloyl groups was studied in seven patients given large amounts of penicillin. Penicilloyl groups were found essentially on the albumin molecule at sites not accessible to anti-penicilloyl antibodies, except after pronase digestion. The amount of penicilloyl groups was proportional to the cumulated doses of penicillin. The decline of penicilloyl groups with time after treatment interruption was exponential. The half-life of penicilloylated albumin was lower than or equal to that of normal albumin. The presence of anti-penicilloyl antibodies was demonstrated in 19 out of 34 penicillin-treated patients (including the seven mentioned above). The relative scarcity of penicillin allergy as compared with the frequent occurrence of anti-penicilloyl antibodies may be partly related to unavailable sites of penicilloyl groups within the albumin molecule.


GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.
Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants' residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level-dependent signal change in this motion-sensitive region. Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level-dependent signal changes-in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined.