Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation.
The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death. There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status. The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.


Quantifying the depth of anesthesia based on brain activity signal modeling.
Various methods of assessing the depth of anesthesia (DoA) and reducing intraoperative awareness during general anesthesia have been extensively studied in anesthesiology. However, most of the DoA monitors do not include brain activity signal modeling. Here, we propose a new algorithm termed the cortical activity index (CAI) based on the brain activity signals. In this study, we enrolled 32 patients who underwent laparoscopic cholecystectomy. Raw electroencephalography (EEG) signals were acquired at a sampling rate of 128 Hz using BIS-VISTA with standard bispectral index (BIS) sensors. All data were stored on a computer for further analysis. The similarities and difference among spectral entropy, the BIS, and CAI were analyzed. Pearson correlation coefficient between the BIS and CAI was 0.825. The result of fitting the semiparametric regression models is the method CAI estimate (-0.00995; P = .0341). It is the estimated difference in the mean of the dependent variable between method BIS and CAI. The CAI algorithm, a simple and intuitive algorithm based on brain activity signal modeling, suggests an intrinsic relationship between the DoA and the EEG waveform. We suggest that the CAI algorithm might be used to quantify the DoA.


Carpal tunnel sonography by the rheumatologist versus nerve conduction study by the neurologist.
To determine the value of sonography (SG) performed by the rheumatologist to diagnose carpal tunnel syndrome (CTS). Sixty-three patients with clinical signs of CTS according to the neurologist, based on patient history and clinical examination, were studied. In the 6 weeks prior to surgery, SG was performed by a rheumatologist and nerve conduction study (NCS) was assessed. Improvement of initial complaints of 90% or more 3 months after surgery was considered to be the post-hoc gold standard for the diagnosis of CTS. After surgery, 47 patients (75%) experienced > or = 90% relief of complaints. Mean cross sectional area of the median nerve for patients with CTS was 11.3 mm2 compared to 6.1 mm2 in the control group. The sensitivity to detect CTS was 0.70 for SG and 0.98 for NCS, and specificity was 0.63 for SG and 0.19 for NCS. Positive predictive value was 0.85 for SG and 0.78 for NCS; negative predictive value was 0.42 for SG and 0.75 for NCS. Accuracy was 0.68 for SG and 0.78 for NCS. CTS can be identified by SG less sensitively but more specifically than by NCS.


Community-acquired pneumonia in children.
Community-acquired pneumonia is a potentially serious infection in children and often results in hospitalization. The diagnosis can be based on the history and physical examination results in children with fever plus respiratory signs and symptoms. Chest radiography and rapid viral testing may be helpful when the diagnosis is unclear. The most likely etiology depends on the age of the child. Viral and Streptococcus pneumoniae infections are most common in preschool-aged children, whereas Mycoplasma pneumoniae is common in older children. The decision to treat with antibiotics is challenging, especially with the increasing prevalence of viral and bacterial coinfections. Preschool-aged children with uncomplicated bacterial pneumonia should be treated with amoxicillin. Macrolides are first-line agents in older children. Immunization with the 13-valent pneumococcal conjugate vaccine is important in reducing the severity of childhood pneumococcal infections.


A comparison of the perceptions and beliefs of workers and owners with regard to workplace safety in small metal fabrication businesses.
Problems of improving safety in small business establishments may include a lack of resources, limited unionization, and an informal management structure. We evaluated worker and manager perceptions of worksite health and safety using Social Cognitive Theory. We used a business safety scorecard to audit the safety conditions, policies and programs, and work practices. Comparisons were made between the different measures. Businesses with safety committees had 1.7-2.1 times higher proportion of positive safety scorecard items than businesses without committees. Union status and business size were not associated with business safety audit results. Non-English-speaking and less educated employees reported higher levels of knowledge about safety than did their more educated and/or English-speaking peers. The presence of a safety committee is the single most important indicator of workplace safety. Self-reported understanding of workplace safety is greater among employees who do not speak English or have lower levels of formal education. Future worksite interventions should consider the need for participatory worksite safety committees. Multilingual training programs would help reach a greater proportion of workers.


The potential impact of pre-exposure prophylaxis for HIV prevention among men who have sex with men and transwomen in Lima, Peru: a mathematical modelling study.
HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.


The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine.
Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various débridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly.


Women's empowerment in agriculture and agricultural productivity: Evidence from rural maize farmer households in western Kenya.
This paper documents a positive relationship between maize productivity in western Kenya and women's empowerment in agriculture, measured using indicators derived from the abbreviated version of the Women's Empowerment in Agriculture Index. Applying a cross-sectional instrumental-variable regression method to a data set of 707 maize farm households from western Kenya, we find that women's empowerment in agriculture significantly increases maize productivity. Although all indicators of women's empowerment significantly increase productivity, there is no significant association between the women's workload (amount of time spent working) and maize productivity. Furthermore, the results show heterogenous effects with respect to women's empowerment on maize productivity for farm plots managed jointly by a male and female and plots managed individually by only a male or female. More specifically, the results suggest that female- and male-managed plots experience significant improvements in productivity when the women who tend them are empowered. These findings provide evidence that women's empowerment contributes not only to reducing the gender gap in agricultural productivity, but also to improving, specifically, productivity from farms managed by women. Thus, rural development interventions in Kenya that aim to increase agricultural productivity-and, by extension, improve food security and reduce poverty-could achieve greater impact by integrating women's empowerment into existing and future projects.


Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade.
Local anesthetic systemic toxicity (LAST) is a potentially life-threatening complication of local anesthetic administration. In this article, the results of the Australian and New Zealand Registry of Regional Anaesthesia were analyzed to determine if ultrasound-guided peripheral nerve blockade (PNB) was associated with a reduced risk of LAST compared with techniques not utilizing ultrasound technology. The period of study for this multicenter study involving 20 hospitals was from January 2007 through May 2012. The primary outcome was LAST comprising minor, major, and cardiac arrest (due to toxicity) events determined using standardized definitions. Multivariable logistic regression models and propensity score analyses were used to determine significant event predictors. The study population comprised 20,021 patients who received 25,336 PNBs. There were 22 episodes of LAST, resulting in an incidence of LAST of 0.87 per 1000 PNBs (95% confidence interval, 0.54-1.3 per 1000). Ultrasound guidance was associated with a reduced incidence of local anesthetic toxicity. Site of injection, local anesthetic type, dose per weight, dose, and patient weight were all predictors of LAST. This study provides the strongest evidence, to date, that ultrasound guidance may improve safety because it is associated with a reduced risk of LAST following PNB.


Promoting Reproducible Research for Characterizing Nonmedical Use of Medications Through Data Annotation: Description of a Twitter Corpus and Guidelines.
Social media data are being increasingly used for population-level health research because it provides near real-time access to large volumes of consumer-generated data. Recently, a number of studies have explored the possibility of using social media data, such as from Twitter, for monitoring prescription medication abuse. However, there is a paucity of annotated data or guidelines for data characterization that discuss how information related to abuse-prone medications is presented on Twitter. This study discusses the creation of an annotated corpus suitable for training supervised classification algorithms for the automatic classification of medication abuse-related chatter. The annotation strategies used for improving interannotator agreement (IAA), a detailed annotation guideline, and machine learning experiments that illustrate the utility of the annotated corpus are also described. We employed an iterative annotation strategy, with interannotator discussions held and updates made to the annotation guidelines at each iteration to improve IAA for the manual annotation task. Using the grounded theory approach, we first characterized tweets into fine-grained categories and then grouped them into 4 broad classes-abuse or misuse, personal consumption, mention, and unrelated. After the completion of manual annotations, we experimented with several machine learning algorithms to illustrate the utility of the corpus and generate baseline performance metrics for automatic classification on these data. Our final annotated set consisted of 16,443 tweets mentioning at least 20 abuse-prone medications including opioids, benzodiazepines, atypical antipsychotics, central nervous system stimulants, and gamma-aminobutyric acid analogs. Our final overall IAA was 0.86 (Cohen kappa), which represents high agreement. The manual annotation process revealed the variety of ways in which prescription medication misuse or abuse is discussed on Twitter, including expressions indicating coingestion, nonmedical use, nonstandard route of intake, and consumption above the prescribed doses. Among machine learning classifiers, support vector machines obtained the highest automatic classification accuracy of 73.00% (95% CI 71.4-74.5) over the test set (n=3271). Our manual analysis and annotations of a large number of tweets have revealed types of information posted on Twitter about a set of abuse-prone prescription medications and their distributions. In the interests of reproducible and community-driven research, we have made our detailed annotation guidelines and the training data for the classification experiments publicly available, and the test data will be used in future shared tasks.


Coffee to reduce risk of type 2 diabetes?: a systematic review.
Type 2 DM is associated with high rates of morbidity and premature mortality. Various potential health effects of coffee have been extensively studied, but data on habitual coffee consumption and the risk of type 2 diabetes mellitus have only recently been published. We systematically reviewed cohort studies (identified after searching through MEDLINE) from the period of January 2001 to August 2011 to find out the relation of degree of coffee consumption with development of diabetes mellitus. Information on study design, participant characteristics, measurement of coffee consumption and outcomes, adjustment for potential confounders, and estimates of associations was reviewed independently by 3 reviewers. The review included 13 cohort studies including 12, 47,387 participants and 9473 incident cases of type 2 diabetes. We compared the risk of diabetes amongst people with different degrees of coffee consumption. We concluded that habitual coffee consumption is associated with a lower risk of type 2 diabetes. Participants who drank 4 to 6 cups and more than 6 to 7 cups of coffee per day had a lower risk of type 2 diabetes compared with those who drank less than 2 cups per day. Advantage of filtered coffee over pot boiled, decaffeinated coffee over caffeinated coffee and stronger inverse correlation in < 60 years age group was also noted. However, based on this review, increasing coffee consumption as a public health strategy can't be recommended. More detailed studies of coffee consumption, including appropriate measures of postprandial hyperglycemia and insulin sensitivity, are required.


Combined Use of Predatory Mirids With Amblyseius swirskii (Acari: Phytoseiidae) to Enhance Pest Management in Sweet Pepper.
The combined release of Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) with Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae) provides effective control of sweet pepper key pests, such as thrips and whiteflies. However, the management of the aphids can still be improved. Recently, the predatory mirids Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) and Macrolophus pygmaeus (Rambur) (Hemiptera: Miridae) have been found to be effective in the control of aphids, thrips and whiteflies when tested alone. Hence, integrating one of these two mirids with A. swirskii might enhance sweet pepper pest management. In this work, we began by investigating the co-occurrence of both mirid species when released together with A. swirskii. This was compared to the standard release of O. laevigatus with A. swirskii. N. tenuis and A. swirskii were involved in a bidirectional intraguild predation (IGP). On the contrary, this interaction (IGP) was apparently unidirectional in the case of M. pygmaeus with A. swirskii and O. laevigatus with A. swirskii. Both, M. pygmaeus and O. laevigatus significantly reduced the abundance of A. swirskii. Secondly, in a greenhouse experiment, where the same release combinations were tested (either N. tenuis, M. pygmaeus or O. laevigatus combined with A. swirskii), IGP seemed to be neutralized. Mirids with A. swirskii significantly suppressed thrips, whitefly, and aphid infestations. Contrarily, the combined use of O. laevigatus with A. swirskii did not reached a satisfactory control for aphids, despite the reduction in thrips and whitefly densities. Therefore, our results suggest that the use of mirids combined with A. swirskii could result in more efficient and robust biological control programs in sweet pepper crops.


Genetic reduction of circulating insulin-like growth factor-1 inhibits azoxymethane-induced colon tumorigenesis in mice.
High levels of insulin-like growth factor-1 (IGF-1) have been associated with a significant increase in colon cancer risk. Additionally, IGF-1 inhibits apoptosis and stimulates proliferation of colonic epithelial cells in vitro. Unfortunately, IGF-1 knockout mice have severe developmental abnormalities and most do not survive, making it difficult to study how genetic ablation of IGF-1 affects colon tumorigenesis. To test the hypothesis that inhibition of IGF-1 prevents colon tumorigenesis, we utilized a preexisting mouse model containing a deletion of the igf1 gene in the liver through a Cre/loxP system. These liver-specific IGF-1 deficient (LID) mice display a 50-75% reduction in circulating IGF-1 levels. We conducted a pilot study to assess the impact of liver-specific IGF-1 deficiency on azoxymethane (AOM)-induced colon tumors. LID mice had a significant inhibition of colon tumor multiplicity in the proximal area of the colon compared to their wild-type littermates. We examined markers of proliferation and apoptosis in the colons of the LID and wild-type mice to see if these were consistent with tumorigenesis. We observed a decrease in proliferation in the colons of the LID mice and an increase in apoptosis. Finally, we examined cytokine levels to determine whether IGF-1 interacts with inflammatory pathways to affect colon tumorigenesis. We observed a significant reduction in the levels of 7 out of 10 cytokines that were measured in the LID mice as compared to wild-type littermates. Results from this pilot study support the hypothesis that reductions in circulating IGF-1 levels may prevent colon tumorigenesis and affect both proliferation and apoptosis. Future experiments will investigate downstream genes of the IGF-1 receptor.


Testing for baseline differences in randomized controlled trials: an unhealthy research behavior that is hard to eradicate.
According to the CONSORT statement, significance testing of baseline differences in randomized controlled trials should not be performed. In fact, this practice has been discouraged by numerous authors throughout the last forty years. During that time span, reporting of baseline differences has substantially decreased in the leading general medical journals. Our own experience in the field of nutrition behavior research however, is that co-authors, reviewers and even editors are still very persistent in their demand for these tests. The aim of this paper is therefore to negate this demand by providing clear evidence as to why testing for baseline differences between intervention groups statistically is superfluous and why such results should not be published. Testing for baseline differences is often propagated because of the belief that it shows whether randomization was successful and it identifies real or important differences between treatment arms that should be accounted for in the statistical analyses. Especially the latter argument is flawed, because it ignores the fact that the prognostic strength of a variable is also important when the interest is in adjustment for confounding. In addition, including prognostic variables as covariates can increase the precision of the effect estimate. This means that choosing covariates based on significance tests for baseline differences might lead to omissions of important covariates and, less importantly, to inclusion of irrelevant covariates in the analysis. We used data from four supermarket trials on the effects of pricing strategies on fruit and vegetables purchases, to show that results from fully adjusted analyses sometimes do appreciably differ from results from analyses adjusted for significant baseline differences only. We propose to adjust for known or anticipated important prognostic variables. These could or should be pre-specified in trial protocols. Subsequently, authors should report results from the fully adjusted as well as crude analyses, especially for dichotomous and time to event data. Based on our arguments, which were illustrated by our findings, we propose that journals in and outside the field of nutrition behavior actively adopt the CONSORT 2010 statement on this topic by not publishing significance tests for baseline differences anymore.


The association between postload plasma glucose levels and 38-year mortality risk of coronary heart disease: the prospective NHLBI Twin Study.
Due to the paucity of direct evidence, we aimed to evaluate whether the association between postload plasma glucose levels (ppGlucose) and long-term risk of mortality from coronary heart disease was independent of or attributable to genes and common environment. From the prospective National Heart, Lung, and Blood Institute (NHLBI) Twin Study, we included 903 middle-aged male twins, who were nondiabetic, free of coronary heart disease at baseline (1969-1973), and followed for up to 38 years for coronary heart, cardiovascular, and all-cause mortality. Frailty survival models were used to estimate hazard ratio (HR) for various associations: overall (equivalent to singleton population association), within-pair (controlling for genes and environment common to co-twins), and between-pair association (reflecting influences of common factors). Overall associations were statistically significant for coronary heart and cardiovascular but not all-cause deaths after controlling for known risk factors. The associations were not statistically significant in within-pair analyses. The within-pair association was not statistically different by zygosity for specific and all-cause death risk. After the full adjustment for known risk factors, HR (95% confidence interval) for within-pair association was 1.07 (0.90, 1.28), 1.06 (0.94, 1.19), and 0.99 (0.94, 1.05) for coronary heart, cardiovascular, and all-cause mortality, respectively. The fully adjusted between-pair associations were statistically significant for specific and all-cause death risk: a 50 mg/dL increase in the mean value of ppGlucose for a twin pair was associated with a raised death risk [HR (95% confidence interval) 1.15 (1.02, 1.30), 1.10 (1.02, 1.20), and 1.05 (1.01, 1.09) for coronary heart, cardiovascular, and all-cause mortality, respectively]. Between-pair association was significant in dizygotic but not in monozygotic twins. The positive association between ppGlucose and long-term coronary heart mortality risk is largely explained by factors shared between co-twins, including familial factors; however, within-pair effects cannot be absolutely excluded.


Risk factors profile of shoulder dystocia in oman: a case control study.
This study aimed to assess the risk factor profile of shoulder dystocia and associated neonatal complications in Oman, a developing Arab country. A retrospective case-control study was conducted among 111 cases with dystocia and 111 controls, identified during 1994-2006 period in a tertiary care hospital in Oman. Controls were randomly selected among women who did not have dystocia, and were matched to cases on the day of delivery. Data related to potential risk factors, delivery, and obstetric complications were collected. Dystocia was significantly associated with older maternal age, higher parity, larger BMI, diabetes, and previous record of dystocia. In addition, dystocia was associated more with vacuum and forceps deliveries. Routine traction (51%) was the most used manoeuvre. Among dystocia cases, 13% were associated with fetal complications of which Erb's Palsy was the most prevalent (79%). Our finding of significant associations with risk factors lays out the ground to develop a predictability index for shoulder dystocia, which would help in making it preventable. Further p rospective studies are required to confirm the obtained results.


Adapting the Individualized Care Scale for cross-cultural comparison.
Cross-cultural comparative studies using reliable and valid instruments can increase awareness of the differences and similarities between health worker's ability to respond to patients' individual needs within different health systems. This will enable a better understanding of cultural perspectives in individualized nursing care. To describe the translation and adaptation process of the Individualized Care Scale (ICS) and examine its reliability and validity in a cross-cultural study. A cross-sectional comparative study. Twenty-seven orthopaedic and trauma in-patient units at 14 hospitals in 5 countries. A total of 1126 patients were included in the study: Finland (n = 425), Greece (n = 315), Sweden (n = 218), UK (n = 135) and USA (n = 33). A systematic forward- and back-translation procedure using bilingual techniques, a committee approach, pretest techniques and pilot testing were used with a convenience sample to produce a valid ICS for each participating group. Psychometric evaluation of the adapted ICS was based on means, SD, missing data analysis, Cronbach's alpha coefficients and average inter-item correlations. Construct validity was examined using sub-scale correlations to total scales and principal components analysis. The use of the range of options and the sub-scale mean scores ranging from 2.72 to 4.30 demonstrated the sensitivity of the scale. Cronbach's alpha coefficients (0.77-0.97) and average inter-item correlations (0.37-0.77) were acceptable. The sub-scale correlations to total scales were high (0.83-0.97). The underlying theoretical construct of the ICS was demonstrated by the explained variances ranging from 58% to 79%. The ICS shows promise as a tool for evaluating individualized care in European cultures. The international expansion of an existing instrument developed for one country facilitates comparative studies across countries. There is a need to further test the construct validity and appropriateness of the ICS in different settings in European and nonwestern cultures.


Making Surgical Care Safer: A Survey on the Implementation of the Checklist by Belgian Surgeons.
The operating theatre (OT) is a complex environment. The purpose of this survey was to evaluate the implementation of the surgical checklist (SC) at individual level by Belgian Surgeons. A Surgical Checklist Questionnaire (SCQ) related to the use of the SC by individual surgeons was attached to the registration website for the 2015 Belgian Surgical Week. It was a one page long, user friendly document, easy to be filled voluntarily and anonymously. Among the 206 surgeons who registered, 81 (39%) filled in the SCQ. The SC template proposed by the WHO "Safe Surgery Saves Lives" initiative was used by 91% of the respondents. However, 89% adapted the SC to their local hospital environment, and 87.5% use it personally for their patients. Since implementation, the SC was never adapted in 46%. According to 21% of respondents, an adverse event was avoided thanks to the SC. Amazingly, SC was considered as an administrative burden by 83% despite the same percentage recognized that patients benefited from the SC. Only 28% of respondents got feedback from the use of the SC. In this survey, the number of adverse event avoided thanks to the use of the SC demonstrates that SC -represents a simple strategy for addressing surgical patient safety in OT. Nevertheless, SC is still considered by many surgeons as an additional administrative burden and/or as just another gimmick. Further studies are needed to understand why some surgeons are still not willing to adapt to a changing safety culture.


Multispectral digital colposcopy for in vivo detection of cervical cancer.
We present a multispectral digital colposcope (MDC) to measure multispectral autofluorescence and reflectance images of the cervix by using an inexpensive color CCD camera. The diagnostic ability of the MDC was evaluated by application of MDC spectral response to fluorescence and reflectance spectra measured from a large clinical trial. High diagnostic performance was achieved by use of only two excitation wavelengths: 330 and 440 nm. Good quality autofluorescence images of the human cervix were acquired in vivo with the MDC. Automated diagnostic algorithms correctly identified CIN (cervical intraepithelial neoplasia) lesions from MDC fluorescence images. The MDC has the potential to provide a costeffective alternative to standard colposcopy and better direction of biopsies.


Barriers to research utilization for oncology staff nurses and nurse managers/clinical nurse specialists.
To describe and compare barriers to research utilization faced by oncology staff nurses and nurse managers/clinical nurse specialists (CNSs) and to compare these to barriers identified by other nurses. Exploratory descriptive. National. Proportional random sample of 2,000 Oncology Nursing Society (ONS) staff nurses (n = 769) from seven practice settings. ONS participants recruited oncology staff nurses (n = 331) and nurse managers/CNSs involved in cancer care (n = 407). Mailings, including a demographic questionnaire and Barriers Scale, were sent to ONS nurses, and reminder postcards were sent to increase the return rate. Barrier categories: characteristics of the adopter (nurse), organization, innovation (research itself), and communication, individual item barriers. Nurse and worksite characteristics. Differences existed in oncology nurses' perceptions of the extent to which the adopter, organization, and innovation characteristics served as obstacles to research utilization. Nurse managers/CNSs perceived that each of these acted as a greater barrier than did staff nurses. Both groups perceived communication characteristics as a moderate barrier. Oncology nurses, as a group, responded similarly to other nurse samples regarding research and communication characteristics. Perceptions of oncology nurse managers/CNSs were similar to those of administrators in other studies. Oncology staff nurses rated barriers lower than nurses, including clinicians, in other samples. For oncology nurses, organization, research, and communication barriers persist as impediments to research utilization. Nurse adopter characteristics may be diminishing as obstacles for staff nurses but not for nurse managers/CNSs. The decreased strength that oncology nurses attributed to barriers may reflect a benefit of practicing nursing in a specialty. Decreasing known barriers would facilitate research-based practice in oncology. Nurse leaders can create environments conducive to research utilization by altering existing mechanisms, facilitating access to nursing research experts, supporting time for research utilization efforts, giving authority for practice changes, and offering continuing education related to research utilization processes. Nurse managers/CNSs need to increase their familiarity with research and research utilization, ensuring their awareness of pertinent clinical findings. Perceptual gaps between staff nurses and nurse managers/CNSs regarding research utilization require discussion and formal investigation. Researchers must communicate in clinician-friendly ways. All nurses need to demand and facilitate access to research findings.


Molecular evidence for resurrection of Plesiochorus elongatus (Digenea: Gorgoderidae): An urinary bladder parasite of sea turtles.
Trematodes of the genus Plesiochorus were recovered from the urinary bladder of a stranded female adult loggerhead sea turtle, Caretta caretta, on a beach in Rio de Janeiro State, Brazil. Morphological analysis of the specimens revealed characteristics resembling the sub-species Plesiochorus cymbiformis elongatus rather than the recently synonymised Plesiochorus cymbiformis. Molecular phylogenetic analysis of the ITS2 region also showed that P. c. elongatus was distinct from P. cymbiformis and related taxa. Further analysis of the ITS2 revealed substantial differentiation between P. cymbiformis from the USA and Brazil and the newly sequenced P. c. elongatus from Brazil, while a previously unspecified Plesiochorus sp. from the USA closely related to the novel Brazilian P. c. elongatus was reconciled as a USA isolate of P. c. elongatus. Based on both the morphological and molecular data it is suggested that P. c. elongatus should be referred to as Plesiochorus elongatus and be considered as the second species in the genus.


Truncation of the human adenovirus type 5 L4 33-kDa protein: evidence for an essential role of the carboxy-terminus in the viral infectious cycle.
The subgroup C human adenovirus L4 33-kDa protein is a nuclear phosphoprotein that plays a direct, but dispensable, role in virion assembly. The r-strand open reading frame (ORF) for this protein lies opposite to the 5' end of the l-strand E2 early (E2E) transcription units. To facilitate studies of regulation of E2E transcription, we wished to construct a mutant virus in which the 33-kDa ORF was truncated to serve as a background into which specific E2E mutations could be introduced without also altering the 33-kDa protein. We constructed viral DNA (vDNA) containing within the 33-kDa ORF two tandem, premature stop codons that should prevent translation of the C-terminal 47 amino acids of the protein (Delta47). We report here the unanticipated lethality of such truncation of the L4 33-kDa protein. Viral DNA harboring the Delta47 mutations did not produce infectious virus when transfected into cultured cells. In contrast, infectious virus was recovered upon transfection of revertant vDNA, indicating that the Delta47 mutations were responsible for the observed phenotype. The Delta47 mutations did not affect E2E transcription or production of the E2 DNA-binding protein. Transfected Delta47 vDNA was replicated and directed the production of early and late viral proteins, including hexon protein in the trimer conformation. However, no virus particles of any kind were produced. We propose that truncation of the adenovirus 33-kDa protein results in a lethal, late block in the infectious cycle during the assembly of progeny virions and discuss the implications of this phenotype for the mechanism of virion assembly.


The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.
The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the discharge of insufficiently treated wastewater effluent.


RhoG regulates gene expression and the actin cytoskeleton in lymphocytes.
RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton. In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes. Optimal function of RhoG for the expression of these genes requires a calcium signal, normally provided by the antigen receptor. In addition, RhoG potentiation of NFAT requires the indirect activity of Rac and Cdc42; however, pathways distinct from those activated by Rac and Cdc42 mediate RhoG activation of NFAT-dependent transcription. Using effector domain mutants of RhoG we found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT-dependent transcription is an actin-dependent process. RhoG also promotes T-cell spreading on fibronectin, a property that is independent of its ability to enhance NFAT-dependent transcription. Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter.


Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.
Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.


Reduction of photobleaching and photodamage in single molecule detection: observing single actin monomer in skeletal myofibrils.
Recent advances in detector technology make it possible to achieve single molecule detection (SMD) in a cell. SMD avoids complications associated with averaging signals from large assemblies and with diluting and disorganizing proteins. However, it requires that cells be illuminated with an intense laser beam, which causes photobleaching and cell damage. To reduce these effects, we study cells on coverslips coated with silver nanoparticle monolayers (NML). Muscle is used as an example. Actin is labeled with a low concentration of fluorescent phalloidin to assure that less than a single molecule in a sarcomere is fluorescent. On a glass substrate, the fluorescence of actin decays in a step-wise fashion, establishing a single molecule detection regime. Single molecules of actin in living muscle are visualized for the first time. NML coating decreases the fluorescence lifetime 17 times and enhances intensity ten times. As a result, fluorescence of muscle bleaches four to five times slower than on glass. Monolayers decrease photobleaching because they shorten the fluorescence lifetime, thus decreasing the time that a fluorophore spends in the excited state when it is vulnerable to oxygen attack. They decrease damage to cells because they enhance the electric field near the fluorophore, making it possible to illuminate samples with weaker light.


Spatial variability in levels of benzene, formaldehyde, and total benzene, toluene, ethylbenzene and xylenes in New York City: a land-use regression study.
Hazardous air pollutant exposures are common in urban areas contributing to increased risk of cancer and other adverse health outcomes. While recent analyses indicate that New York City residents experience significantly higher cancer risks attributable to hazardous air pollutant exposures than the United States as a whole, limited data exist to assess intra-urban variability in air toxics exposures. To assess intra-urban spatial variability in exposures to common hazardous air pollutants, street-level air sampling for volatile organic compounds and aldehydes was conducted at 70 sites throughout New York City during the spring of 2011. Land-use regression models were developed using a subset of 59 sites and validated against the remaining 11 sites to describe the relationship between concentrations of benzene, total BTEX (benzene, toluene, ethylbenzene, xylenes) and formaldehyde to indicators of local sources, adjusting for temporal variation. Total BTEX levels exhibited the most spatial variability, followed by benzene and formaldehyde (coefficient of variation of temporally adjusted measurements of 0.57, 0.35, 0.22, respectively). Total roadway length within 100 m, traffic signal density within 400 m of monitoring sites, and an indicator of temporal variation explained 65% of the total variability in benzene while 70% of the total variability in BTEX was accounted for by traffic signal density within 450 m, density of permitted solvent-use industries within 500 m, and an indicator of temporal variation. Measures of temporal variation, traffic signal density within 400 m, road length within 100 m, and interior building area within 100 m (indicator of heating fuel combustion) predicted 83% of the total variability of formaldehyde. The models built with the modeling subset were found to predict concentrations well, predicting 62% to 68% of monitored values at validation sites. Traffic and point source emissions cause substantial variation in street-level exposures to common toxic volatile organic compounds in New York City. Land-use regression models were successfully developed for benzene, formaldehyde, and total BTEX using spatial indicators of on-road vehicle emissions and emissions from stationary sources. These estimates will improve the understanding of health effects of individual pollutants in complex urban pollutant mixtures and inform local air quality improvement efforts that reduce disparities in exposure.


The efficacy of therapeutic ultrasound for rotator cuff tendinopathy: A systematic review and meta-analysis.
A systematic review and meta-analysis on the efficacy of therapeutic ultrasound (US) in adults suffering from rotator cuff tendinopathy. A literature search was conducted in four databases for randomized controlled trials (RCT) published until 12/2013, comparing the efficacy of US to any other interventions in adults suffering from rotator cuff tendinopathy. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of included studies. Data were summarized qualitatively or quantitatively. Eleven RCTs with a low mean methodological score (50.0% ± 15.6%) were included. Therapeutic US did not provide greater benefits than a placebo intervention or advice in terms of pain reduction and functional improvement. When provided in conjunction with exercise, US therapy is not superior to exercise alone in terms of pain reduction and functional improvement (pooled mean difference of the Constant-Murley score: -0.26 with 95% confidence interval of -3.84 to 3.32). Laser therapy was found superior to therapeutic US in terms of pain reduction. Based on low to moderate level evidence, therapeutic US does not provide any benefit compared to a placebo or advice, to laser therapy or when combined to exercise. More methodologically sound studies on the efficacy of therapeutic US are warranted.


Curriculum Mapping with Academic Analytics in Medical and Healthcare Education.
No universal solution, based on an approved pedagogical approach, exists to parametrically describe, effectively manage, and clearly visualize a higher education institution's curriculum, including tools for unveiling relationships inside curricular datasets. We aim to solve the issue of medical curriculum mapping to improve understanding of the complex structure and content of medical education programs. Our effort is based on the long-term development and implementation of an original web-based platform, which supports an outcomes-based approach to medical and healthcare education and is suitable for repeated updates and adoption to curriculum innovations. We adopted data exploration and visualization approaches in the context of medical curriculum innovations in higher education institutions domain. We have developed a robust platform, covering detailed formal metadata specifications down to the level of learning units, interconnections, and learning outcomes, in accordance with Bloom's taxonomy and direct links to a particular biomedical nomenclature. Furthermore, we used selected modeling techniques and data mining methods to generate academic analytics reports from medical curriculum mapping datasets. We present a solution that allows users to effectively optimize a curriculum structure that is described with appropriate metadata, such as course attributes, learning units and outcomes, a standardized vocabulary nomenclature, and a tree structure of essential terms. We present a case study implementation that includes effective support for curriculum reengineering efforts of academics through a comprehensive overview of the General Medicine study program. Moreover, we introduce deep content analysis of a dataset that was captured with the use of the curriculum mapping platform; this may assist in detecting any potentially problematic areas, and hence it may help to construct a comprehensive overview for the subsequent global in-depth medical curriculum inspection. We have proposed, developed, and implemented an original framework for medical and healthcare curriculum innovations and harmonization, including: planning model, mapping model, and selected academic analytics extracted with the use of data mining.


The role of liquid-liquid transition in glass formation of CuZr alloys.
Some glass-forming liquids have different liquid phases that have the same composition but different structure, density and entropy. Based on experimental and molecular dynamics simulation, we here report thermodynamic, dynamic, and structural evidence of the liquid-liquid transition (LLT) in ten Cu-Zr glass-forming liquids well above the liquidus temperature. We find that for Cu-Zr alloys, the LLT is beneficial to glass formation, and there is a close relationship between the relative transition strength (RTS) of the LLT and the critical thickness representing the glass forming ability (GFA): the bigger the value of the RTS parameters, the stronger the GFA of Cu-Zr alloys. This work not only uncovers the role of the LLT of melts in the glass formation of solids, but also sheds light on the inheritance of properties of glassy solids from the aspect of the detectable dynamics of high-temperature melts.


Mutations that affect lamB gene expression at a posttranscriptional level.
We previously obtained strains of Escherichia coli in which the beginning of gene lacZ, which codes for beta-galactosidase, is replaced by the beginning of gene lamB, which codes for a maltose-inducible outer membrane protein. In some of these strains the induction (with maltose) of lamB-lacZ hybrid protein synthesis was lethal because of membrane damage resulting from an incomplete export of this protein to the outer membrane. We describe here a class of maltose-resistant mutants obtained from one such strain. Mutants in this class fail to produce the lamB-lacZ hybrid protein but retain the ability to express lacY, which is located distal to the hybrid gene. Some of the mutants carry deletions within the hybrid gene. The others carry point mutations which most probably affect the initiation of translation at the beginning of the hybrid gene. One of these is located in the sequence that codes for the presumed ribosome interaction site on the mRNA. Three others, of which two are located in the coding region (sixth codon), are believed to result in an alteration of mRNA secondary structure such that the accessibility of the ribosome interaction site is reduced.


Electro-optical sensor with spatial and spectral filtering capability.
We describe a new concept of an electro-optical sensor with the capability of simultaneous spatial and spectral filtering. It is based on a spatial light modulator, and in combination with the technique of wavelength multiplexing, it enables one to manipulate the spectral content of an indicated spot within the field of view of the sensor. This new concept allows the attenuation of monochromatic light of undetermined wavelengths in particular and is of worth for imaging vision systems to suppress unwanted detector overexposure.


Regulation of leg size and shape by the Dachsous/Fat signalling pathway during regeneration.
An amputated cricket leg regenerates all missing parts with normal size and shape, indicating that regenerating blastemal cells are aware of both their position and the normal size of the leg. However, the molecular mechanisms regulating this process remain elusive. Here, we use a cricket model to show that the Dachsous/Fat (Ds/Ft) signalling pathway is essential for leg regeneration. We found that knockdown of ft or ds transcripts by regeneration-dependent RNA interference (rdRNAi) suppressed proliferation of the regenerating cells along the proximodistal (PD) axis concomitantly with remodelling of the pre-existing stump, making the regenerated legs shorter than normal. By contrast, knockdown of the expanded (ex) or Merlin (Mer) transcripts induced over-proliferation of the regenerating cells, making the regenerated legs longer. These results are consistent with those obtained using rdRNAi during intercalary regeneration induced by leg transplantation. We present a model to explain our results in which the steepness of the Ds/Ft gradient controls growth along the PD axis of the regenerating leg.


Venus's southern polar vortex reveals precessing circulation.
Initial images of Venus's south pole by the Venus Express mission have shown the presence of a bright, highly variable vortex, similar to that at the planet's north pole. Using high-resolution infrared measurements of polar winds from the Venus Express Visible and Infrared Thermal Imaging Spectrometer (VIRTIS) instrument, we show the vortex to have a constantly varying internal structure, with a center of rotation displaced from the geographic south pole by ~3 degrees of latitude and that drifts around the pole with a period of 5 to 10 Earth days. This is indicative of a nonsymmetric and varying precession of the polar atmospheric circulation with respect to the planetary axis.


Affective neuroscience and psychophysiology: toward a synthesis.
This article reviews the author's program of research on the neural substrates of emotion and affective style and their behavioral and peripheral biological correlates. Two core dimensions along which affect is organized are approach and withdrawal. Some of the key circuitry underlying approach and withdrawal components of emotion is reviewed with an emphasis on the role played by different sectors of the prefrontal cortex (PFC) and amygdala. Affective style refers to individual differences in valence-specific features of emotional reactivity and regulation. The different parameters of affective style can be objectively measured using specific laboratory probes. Relations between individual differences in prefrontal and amygdala function and specific components of affective style are illustrated. The final section of the article concludes with a brief discussion of plasticity in the central circuitry of emotion and the possibility that this circuitry can be shaped by training experiences that might potentially promote a more resilient, positive affective style. The implications of this body of work for a broader conception of psychophysiology and for training the next generation of psychophysiologists are considered in the conclusion.


Outcome Expectations of Total Knee Arthroplasty Patients: The Influence of Demographic Factors, Pain, Personality Traits, Physical and Psychological Status.
Unfulfilled preoperative expectations have a strong influence on the outcome after total knee arthroplasty (TKA). More insight into determinants of the level of expectations is useful in identifying patients at risk for having expectations of the treatment result that are too high or too low. This information can be used in optimizing preoperative expectation management. The aim of the current study was to analyze to what extent preoperative outcome expectations of TKA patients are affected by psychological factors, demographic factors, pain, physical function, and general health status. We performed a cross-sectional analysis of 204 patients with symptomatic and radiographic knee osteoarthritis (OA), scheduled for primary TKA. Outcome expectations were measured using the hospital for special surgery knee replacement expectations survey. Independent variables included were age, sex, body mass index, and patient-reported outcome measures for pain, physical function, quality of life, anxiety, depression, catastrophizing, optimism, and pessimism. Multiple linear regression analyses were used to evaluate associations between these variables and preoperative outcome expectations. Female sex, higher age, higher depression score, and duration of complaints > 50 months showed to be significant predictors of lower expectations for the treatment outcome after TKA. Baseline pain and function scores were not related to the level of preoperative expectations. The present study aids in identifying patients at risk for having either too high or too low expectations. This knowledge can be utilized in individualized expectation management interventions.


Typing of Treponema hyodysenteriae by restriction endonuclease analysis.
Restriction endonuclease analysis (REA) was used to type eight well-characterised strains of Treponema hyodysenteriae originating from the U.K., Canada and the U.S.A., and 16 isolates from cases of swine dysentery in Western Australia (W.A.). Several of the W.A. isolates were also serotyped by the method of Baum and Joens (1979), and the two typing techniques were compared. REA typing was more discriminatory than serotyping, being able to distinguish strains within serotypes. The new technique was neither more difficult nor more time-consuming to perform than serotyping. Within the 16 W.A. isolates, three different REA patterns were identified, with common patterns found on different farms. The eight overseas strains had seven different REA patterns, all of which could be distinguished from the patterns of the W.A. isolates.


STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors.
Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins and early metastasis. Compelling evidence suggests that elevated levels of intracellular oxidative stress contribute to enhanced aggressiveness of numerous cancers, possibly including Ewing tumors. Using comprehensive microarray analyses and RNA interference, we identified the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound mesenchymal stem cell marker of unknown function-as a highly expressed protein in Ewing tumors compared with benign tissues and show its regulation by EWS/FLI1. In addition, we show that STEAP1 knockdown reduces Ewing tumor proliferation, anchorage-independent colony formation as well as invasion in vitro and decreases growth and metastasis of Ewing tumor xenografts in vivo. Moreover, transcriptome and proteome analyses as well as functional studies revealed that STEAP1 expression correlates with oxidative stress responses and elevated levels of reactive oxygen species that in turn are able to regulate redox-sensitive and proinvasive genes. In synopsis, our data suggest that STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors and point to a hitherto unanticipated oncogenic function of STEAP1.


Toll-like receptor activation during cutaneous allergen sensitization blocks development of asthma through IFN-gamma-dependent mechanisms.
Toll-like receptors (TLRs) are pattern-recognition receptors that have a pivotal role as primary sensors of microbial products and as initiators of innate and adaptive immune responses. We investigated the role of TLR2, TLR3, and TLR4 activation during cutaneous allergen sensitization in the modulation of allergic asthma. The results show that dermal exposure to TLR4 ligand lipopolysaccharide (LPS) or TLR2 ligand Pam3Cys suppresses asthmatic responses by reducing airway hyperreactivity, mucus production, Th2-type inflammation in the lungs, and IgE antibodies in serum in a dose-dependent manner. In contrast, TLR3 ligand Poly(I:C) did not protect the mice from asthmatic symptoms but reduced IgE and induced IgG2a in serum. LPS (especially) and Pam3Cys enhanced the activation of dermal dendritic cell (DCs) by increasing the expression of CD80 and CD86 but decreased DC numbers in draining lymph nodes at early time points. Later, these changes in DCs led to an increased number of CD8(+) T cells and enhanced the production of IFN-γ in bronchoalveolar lavage fluid. In conclusion, dermal exposure to LPS during sensitization modulates the asthmatic response by skewing the Th1/Th2 balance toward Th1 by stimulating the production of IFN-γ. These findings support the hygiene hypothesis and pinpoint the importance of dermal microbiome in the development of allergy and asthma.


Th2 cytokines differentially regulate psoriasin expression in human nasal epithelia.
Psoriasin is known to be expressed in diverse organs, where it exerts antimicrobial activity. Psoriasin is also involved in the local host defense mechanism against pathogens. We hypothesized that allergy-related T-helper cell type 2 (Th2) cytokines may regulate the expression of psoriasin. We treated normal human nasal epithelial (NHNE) cells with IL-4 or IL-13. Using human nasal tissues, we compared the expression level of psoriasin. We performed real-time polymerase chain reaction and Western blot assays using NHNE cells. Immunohistochemical staining and Western blot assays were performed with human nasal tissues. Furthermore, we studied the antimicrobial activity of nasal secretions from normal and allergic rhinitis patients. IL-13 markedly down-regulated psoriasin expression at the gene and protein levels in NHNE cells, and it also decreased the amount of psoriasin protein that was secreted into the extracellular compartment in NHNE cells. IL-4 had no statistically significant effect. Results from immunohistochemical staining and Western blot assays showed that psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. Nasal secretions of allergic rhinitis patients exhibited decreased antimicrobial activity compared with control subjects. We found that Th2 cytokines regulated psoriasin expression in NHNE cells, and psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. The decreased expression of psoriasin may be related to the reduction in antimicrobial capacity of nasal secretions under allergic conditions, resulting in an increase in susceptibility to viruses or bacterial infections.


Hyperpolarised magnetic resonance for in vivo real-time metabolic imaging.
Although non-invasive perfusion and viability imaging often provide the gateway to coronary revascularisation, current non-invasive imaging methods only report the surrogate markers of inducible hypoperfusion and presence or absence of myocardial scar, rather than actually visualising areas of ischaemia and/or viable myocardium. This may lead to suboptimal revascularisation decisions. Normally respiring (viable) cardiomyocytes convert pyruvate to acetyl-CoA and CO2/bicarbonate (via pyruvate dehydrogenase), but under ischaemic conditions characteristically shift this conversion to lactate (by lactate dehydrogenase). Imaging pyruvate metabolism thus has the potential to improve upon current imaging techniques. Using the novel hyperpolarisation technique of dynamic nuclear polarisation (DNP), the magnetic resonance signal of injected [1-13C]pyruvate can be transiently magnified >10 000 times over that seen in conventional MR spectroscopy, allowing the characteristic metabolic signatures of ischaemia (lactate production) and viability (CO2/bicarbonate production) to be directly imaged. As such DNP imaging of the downstream metabolism of [1-13C]pyruvate could surpass the diagnostic capabilities of contemporary ischaemia and viability testing. Here we review the technique, and with brief reference to the salient biochemistry, discuss its potential applications within cardiology. These include ischaemia and viability testing, and further characterisation of the altered metabolism seen at different stages during the natural history of heart failure.


Anti-inflammatory activity and molecular mechanism of delphinidin 3-sambubioside, a Hibiscus anthocyanin.
Delphinidin 3-sambubioside (Dp3-Sam), a Hibiscus anthocyanin, was isolated from the dried calices of Hibiscus sabdariffa L, which has been used for folk beverages and herbal medicine although the molecular mechanisms are poorly defined. Based on the properties of Dp3-Sam and the information of inflammatory processes, we investigated the anti-inflammatory activity and molecular mechanisms in both cell and animal models in the present study. In the cell model, Dp3-Sam and Delphinidin (Dp) reduced the levels of inflammatory mediators including iNOS, NO, IL-6, MCP-1, and TNF-α induced by LPS. Cellular signaling analysis revealed that Dp3-Sam and Dp downregulated NF-κB pathway and MEK1/2-ERK1/2 signaling. In animal model, Dp3-Sam and Dp reduced the production of IL-6, MCP-1 and TNF-α and attenuated mouse paw edema induced by LPS. Our in vitro and in vivo data demonstrated that Hibiscus Dp3-Sam possessed potential anti-inflammatory properties.


Design and characterization of a single channel two-liquid capacitor and its application to hyperelastic strain sensing.
Room temperature liquid-metal microfluidic devices are attractive systems for hyperelastic strain sensing. These liquid-phase electronics are intrinsically soft and retain their functionality even when stretched to several times their original length. Currently two types of liquid metal-based strain sensors exist for in-plane measurements: single-microchannel resistive and two-microchannel capacitive devices. With a winding serpentine channel geometry, these sensors typically have a footprint of about a square centimeter. This large footprint of an individual device limits the number of sensors that can be embedded into, for example, electronic fabric or skin. In this work we introduce an alternative capacitor design consisting of two liquid metal electrodes separated by a liquid dielectric material within a single straight channel. Using a liquid insulator instead of a solid elastomer enables us to tailor the system's capacitance by selecting high or low dielectric constant liquids. We quantify the effects of the electrode geometry including the diameter, spacing, and meniscus shape as well as the dielectric constant of the insulating liquid on the overall system's capacitance. We also develop a procedure for fabricating the two-liquid capacitor within a single straight polydiemethylsiloxane channel and demonstrate that this device can have about 25 times higher capacitance per sensor's base area when compared to two-channel liquid metal capacitors. Lastly, we characterize the response of this compact device to strain and identify operational issues arising from complex hydrodynamics near liquid-liquid and liquid-elastomer interfaces.


Automatic Detection of Diabetic Retinopathy in Retinal Fundus Photographs Based on Deep Learning Algorithm.
To achieve automatic diabetic retinopathy (DR) detection in retinal fundus photographs through the use of a deep transfer learning approach using the Inception-v3 network. A total of 19,233 eye fundus color numerical images were retrospectively obtained from 5278 adult patients presenting for DR screening. The 8816 images passed image-quality review and were graded as no apparent DR (1374 images), mild nonproliferative DR (NPDR) (2152 images), moderate NPDR (2370 images), severe NPDR (1984 images), and proliferative DR (PDR) (936 images) by eight retinal experts according to the International Clinical Diabetic Retinopathy severity scale. After image preprocessing, 7935 DR images were selected from the above categories as a training dataset, while the rest of the images were used as validation dataset. We introduced a 10-fold cross-validation strategy to assess and optimize our model. We also selected the publicly independent Messidor-2 dataset to test the performance of our model. For discrimination between no referral (no apparent DR and mild NPDR) and referral (moderate NPDR, severe NPDR, and PDR), we also computed prediction accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and κ value. The proposed approach achieved a high classification accuracy of 93.49% (95% confidence interval [CI], 93.13%-93.85%), with a 96.93% sensitivity (95% CI, 96.35%-97.51%) and a 93.45% specificity (95% CI, 93.12%-93.79%), while the AUC was up to 0.9905 (95% CI, 0.9887-0.9923) on the independent test dataset. The κ value of our best model was 0.919, while the three experts had κ values of 0.906, 0.931, and 0.914, independently. This approach could automatically detect DR with excellent sensitivity, accuracy, and specificity and could aid in making a referral recommendation for further evaluation and treatment with high reliability. This approach has great value in early DR screening using retinal fundus photographs.


Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal, progressive paralysis arising from the premature death of motor neurons. An inherited form is caused by a dominant mutation in the ubiquitously expressed superoxide dismutase (SOD1). SOD1 mutant expression within motor neurons is a determinant of onset and early disease, and mutant accumulation within microglia accelerates disease progression. Muscle also is a likely primary source for toxicity, because retraction of motor axons from synaptic connections to muscle is among the earliest presymptomatic events. To test involvement of muscle in ALS, viral delivery of transcription-mediated siRNA is shown to suppress mutant SOD1 accumulation within muscle alone but to be insufficient to maintain grip strength, whereas delivery to both motor neurons and muscle is sufficient. Use of a deletable mutant gene to diminish mutant SOD1 from muscle did not affect onset or survival. Finally, follistatin expression encoded by adeno-associated virus chronically inhibited myostatin and produced sustained increases in muscle mass, myofiber number, and fiber diameter, but these increases did not affect survival. Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression.


Effect of methanolic extract of Lagenaria siceraria (Molina) Standley fruits on marble-burying behavior in mice: Implications for obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder and is diagnosed nearly as often as asthma and diabetes mellitus. Over the last decade, the inhibition of burying of glass marbles by mice has been used as an index of anti-OCD drug action in the so-called marble-burying test. Lagenaria siceraria (Molina) Standley (LS), commonly known as "bottle gourd" (English), possesses several medicinal properties; little is known about its action as a nerve tonic. The purpose of this study was to characterize the anti-OCD (anti-compulsive) activity of the methanolic extract of the fruits of L. siceraria (Molina) Standley (LS) using the marble-burying behavior in mice. The experiment was conducted in specific animal models of Swiss albino mice to evaluate marble-burying behavior. Intraperitonial administration of 25 and 50 mg/kg of LS extract significantly (P < 0.001) decreased the total number of buried marbles. The effect was comparable to that of the fluoxetine (10 mg/kg, i.p.). Fluoxetine and LS fruit extract do not produce any overt motor dysfunction. Preliminary phytochemical screening of the methanolic extract of LS showed the presence of flavonoids, saponins, sterols, proteins, tannins and carbohydrates. The results of the study for the first time show that the plant possesses anti-compulsive (anti-OCD) activity, confirming the traditional claims. Future research should focus on the identification and the mechanism of action of the constituents from this plant.


The dragons of inaction: psychological barriers that limit climate change mitigation and adaptation.
Most people think climate change and sustainability are important problems, but too few global citizens engaged in high-greenhouse-gas-emitting behavior are engaged in enough mitigating behavior to stem the increasing flow of greenhouse gases and other environmental problems. Why is that? Structural barriers such as a climate-averse infrastructure are part of the answer, but psychological barriers also impede behavioral choices that would facilitate mitigation, adaptation, and environmental sustainability. Although many individuals are engaged in some ameliorative action, most could do more, but they are hindered by seven categories of psychological barriers, or "dragons of inaction": limited cognition about the problem, ideological world views that tend to preclude pro-environmental attitudes and behavior, comparisons with key other people, sunk costs and behavioral momentum, discredence toward experts and authorities, perceived risks of change, and positive but inadequate behavior change. Structural barriers must be removed wherever possible, but this is unlikely to be sufficient. Psychologists must work with other scientists, technical experts, and policymakers to help citizens overcome these psychological barriers.


Why lifespans are more variable among blacks than among whites in the United States.
Lifespans are both shorter and more variable for blacks than for whites in the United States. Because their lifespans are more variable, there is greater inequality in length of life-and thus greater uncertainty about the future-among blacks. This study is the first to decompose the black-white difference in lifespan variability in America. Are lifespans more variable for blacks because they are more likely to die of causes that disproportionately strike the young and middle-aged, or because age at death varies more for blacks than for whites among those who succumb to the same cause? We find that it is primarily the latter. For almost all causes of death, age at death is more variable for blacks than it is for whites, especially among women. Although some youthful causes of death, such as homicide and HIV/AIDS, contribute to the black-white disparity in variance, those contributions are largely offset by the higher rates of suicide and drug poisoning deaths for whites. As a result, differences in the causes of death for blacks and whites account, on net, for only about one-eighth of the difference in lifespan variance.


Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.
The role of inhalational combination therapy when treating carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72-h in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three P. aeruginosa isolates (CZA [ceftazidime/avibactam] MICs, 4/4 to 8/4 μg/ml; AMK-I MICs, 8 to 64 μg/ml) and three K. pneumoniae isolates (CZA MICs, 1/4 to 8/4 μg/ml; AMK-I MICs, 32 to 64 μg/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three P. aeruginosa isolates (-4.14 log10 CFU/ml, P = 0.027; -1.42 log10 CFU/ml, P = 0.020; and -0.4 log10 CFU/ml, P = 0.298) and two of three K. pneumoniae isolates (0.04 log10 CFU/ml, P = 0.963; -4.34 log10 CFU/ml, P < 0.001; and -2.34 log10 CFU/ml, P = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae isolate harboring blaKPC-3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.


Use of bile-esculin agar for rapid differentiation of Enterobacteriaceae.
Bile-esculin agar has been used for several years for the presumptive identification of group D streptococci. All members of the Enterobacteriaceae family will also grow on this medium, but only certain ones can hydrolyze esculin to 6,7-dihydroxycoumarin, which reacts with iron to produce a characteristic blackening of the medium. One thousand and six cultures from clinical specimens representing 20 genera were isolated and identified. Heavy inocula from fresh pure culture isolates on heart infusion agar were placed on bile-esculin agar slants and incubated at 35 C. The slants were examined at 4 h and again at 18 h for esculin hydrolysis. Shigella, Salmonella, Arizona, Proteus mirabilis, Proteus morganii, Providencia alcalifaciens, and Providencia stuartii all produced negative results. Klebsiella pneumoniae, Enterobacter aerogenes, Serratia marcescens, and Serratia rubidaea produced a positive reaction in 4 h. The other remaining eight genera exhibited varying results. The use of this medium in conjunction with triple sugar iron-lysine iron agar has been of great value in differentiating the Klebsiella-Enterobacter-Serratia group from other Enterobacteriaceae.


The Role of Exercise in a Weight-Loss Program on Clinical Control in Obese Adults with Asthma. A Randomized Controlled Trial.
Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated. To examine the effect of exercise training in a weight-loss program on asthma control, quality of life, inflammatory biomarkers, and lung function. Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises. The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile], -0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean ± SD, -6.8% ± 3.5 vs. -3.1% ± 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O2 × kg-1 × min-1; P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation. Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients. Clinical trial registered with www.clinicaltrials.gov (NCT 02188940).


Heterogeneity of healthy aging: comparing long-lived families across five healthy aging phenotypes of blood pressure, memory, pulmonary function, grip strength, and metabolism.
Five healthy aging phenotypes were developed in the Long Life Family Study to uncover longevity pathways and determine if healthy aging across multiple systems clustered in a subset of long-lived families. Using blood pressure, memory, pulmonary function, grip strength, and metabolic measures (body mass index, waist circumference and fasting levels of glucose, insulin, triglycerides, lipids, and inflammatory markers), offspring were ranked according to relative health using gender-, age-, and relevant confounder-adjusted z-scores. Based on our prior work, families met a healthy aging phenotype if ≥ 2 and ≥ 50% of their offspring were exceptionally healthy for that respective phenotype. Among 426 families, only two families met criteria for three healthy aging phenotypes and none met criteria for four or more healthy aging phenotypes. Using Spearman correlation, the proportion of offspring within families with exceptionally healthy pulmonary function was correlated with the proportion of offspring within families with exceptional strength (r = 0.19, p = 0.002). The proportion of offspring within families meeting the healthy blood pressure and metabolic phenotypes were also correlated (r = 0.14, p = 0.006), and more families were classified as meeting healthy blood pressure and metabolic phenotypes (Kappa = 0.10, p = 0.02), as well as the healthy pulmonary and blood pressure phenotypes than expected by chance (Kappa = 0.09, p = 0.03). Other phenotypes were weakly correlated (|r| ≤ 0.07) with low pairwise agreement (Kappa ≤ 0.06). Among these families selected for familial longevity, correspondence between healthy aging phenotypes was weak, supporting the heterogeneous nature of longevity and suggesting biological underpinnings of each individual phenotype should be examined separately to determine their shared and unique determinants.


Regulation of postprandial mesenteric blood flow in humans: evidence for a cholinergic nervous reflex.
Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to determine the physiological importance of postprandial blood concentrations of cholecystokinin octapeptide (CCK8), gastrin 17, secretin, and glucagon and to study whether a nervous cholinergic reflex mechanism has a role in the postprandial mesenteric blood flow response. Duplex parameters of vessel diameter, mean velocity, and flow volume were determined serially in the basal state and after stimulation. Changes were compared with baseline values. Superior mesenteric artery parameters were significantly increased over baseline values after a liquid test meal, but ingestion of saline did not cause any changes. Hormones infused simultaneously at postprandial concentrations did not change mesenteric blood flow. When they were infused at pharmacological doses, however, a significant increase in flow parameters was observed. Pretreatment with atropine significantly (p less than 0.05) reduced the mesenteric blood flow response to meal stimulation (57%). These data suggest that the four hormones tested are not of quantitative importance in regulating postprandial superior mesenteric artery blood flow. A cholinergic nervous reflex, however, participates in the control of food induced mesenteric artery flow changes.


Study of operation dynamics for crystal temperature measurement in a diode end-pumped monolithic Yb:YAG laser.
A temperature measurement scheme was proposed in a diode end-pumped thin monolithic Yb:YAG laser by analyzing the red-shifting behaviors of each lasing peak. The amount of peak shift was measured on the basis of the threshold lasing spectrum by using a chopped pump beam. In order to determine the effective scale factor, the ratio between the peak shift and the temperature rise, the dynamics of the spectral shift, the output beam profile, and the output power were investigated. The effective scale factor was determined to be about 0.0114 nm/°C in the case of the crystal sandwiched by copper bocks with a hole, wherein the plane stress approximation is valid. On the other hand, the effective scale factor significantly decreased in the case of the crystal sandwiched by sapphire plates.


CoOx(OH)y/C nanocomposites in situ derived from Na4Co3(PO4)2P2O7 as sustainable electrocatalysts for water splitting.
The great interest in developing efficient and stable bifunctional electrodes for electrocatalytic water splitting is due to the rapid growth in demand for sustainable and renewable energy sources. Here, we present an original electrode design strategy which can be used for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER). This strategy is based on the direct formation of active catalytic material on the electrode surface during electrolysis. In our case, cobalt hydroxides (β-Co(OH)2 and CoO(OH) for HER and OER, respectively) in a carbon matrix are produced by the chemical and electrochemical transformation of various forms (glass, glass-ceramic and polycrystalline) of Na4Co3(PO4)2P2O7 during electrolysis in 1 M NaOH solution. The CoOx(OH)y/C composites demonstrate remarkable stability over time (more than 50 h), and bifunctional catalytic activity with an overall water splitting potential close to 1.8 V at a current density of 10 mA cm-2. The range of overpotentials for OER and HER is 346-365 and 326-369 mV, respectively. These electrodes can invert the OER and HER processes with a total overpotential of 0.6 V in the cell. This remarkable CoO(OH) ↔ Co(OH)2 inversion in the carbon matrix its further utility for creating bifunctional electrodes for long-life water splitting cells.


A pilot study to investigate shoulder muscle fatigue during a sustained isometric wheelchair-propulsion effort using surface EMG.
The primary aim of this pilot study was to develop a testing protocol for gathering shoulder muscle surface electromyography (EMG) data during a sustained submaximal isometric wheelchair-propulsion effort. Of special interest was analysis of the median frequency of the surface EMG signal power spectrum; a negative median frequency shift during a sustained effort is an indicator of muscle fatigue. The long-term goal is to improve our understanding of how fatigue and muscle imbalance might play a role in the development of a broad array of upper-extremity overuse syndromes. Participants were a convenience sample of seven male manual-wheelchair users with spinal cord injury and 14 able-bodied males. Surface EMG in six right-side shoulder muscles was recorded while subjects resisted a static force equal to 60% of their maximum wheelchair-propulsion strength until fatigued. Percent of maximum voluntary contraction and the median frequency shift for each muscle were analyzed. The able-bodied group used a higher percent of maximum than the manual-wheelchair group (p< .05), and a more pronounced negative median frequency shift was evident in the able-bodied group (p < .10). Patterns that emerged suggest that spectral analysis of the surface electromyographhic signal has promise as a clinically useful tool to authenticate muscle fatigue in the upper extremities during occupational performance. Such data in the future could be used to justify the need for and benefits of adapted performance techniques and assistive technology.


Effect of training mode on post-exercise heart rate recovery of trained cyclists.
The sympathetic nervous system dominates the regulation of body functions during exercise. Therefore after exercise, the sympathetic nervous system withdraws and the parasympathetic nervous system helps the body return to a resting state. In the examination of this relationship, the purpose of this study was to compare recovery heart rates (HR) of anaerobically versus aerobically trained cyclists. With all values given as means ± SD, anaerobically trained track cyclists (n=10, age=25.9 ± 6.0 yrs, body mass=82.7 ± 7.1 kg, body fat=10.0 ± 6.3%) and aerobically trained road cyclists (n=15, age=39.9 ± 8.5 yrs, body mass=75.3 ± 9.9 kg, body fat=13.1 ± 4.5%) underwent a maximal oxygen uptake test. Heart rate recovery was examined on a relative basis using heart rate reserve as well as the absolute difference between maximum HR and each of two recovery HRs. The post-exercise change in HR at minute one for the track cyclists and road cyclists respectively were 22 ± 8 bpm and 25 ± 12 bpm. At minute two, the mean drop for track cyclists was significantly (p<0.05) greater than the road cyclists (52 ± 15 bpm and 64 ± 11 bpm). Training mode showed statistically significant effects on the speed of heart rate recovery in trained cyclists. Greater variability in recovery heart rate at minute two versus minute one suggests that the heart rate should be monitored longer than one minute of recovery for a better analysis of post-exercise autonomic shift.


Health Benefits In 2017: Stable Coverage, Workers Faced Considerable Variation In Costs.
The annual Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey found that in 2017, average annual premiums (employer and worker contributions combined) rose 4 percent for single coverage, to $6,690, and 3 percent for family coverage, to $18,764. Covered workers contributed 18 percent of the premium for single coverage and 31 percent for family coverage, on average, although there was considerable variation around these averages. For covered workers in small firms, 10 percent did not make a premium contribution for family coverage, while 36 percent made a contribution of more than half of their premium. The average worker contribution for family coverage has increased from $4,316 in 2012 to $5,714 in 2017. The share of firms that offered health benefits (53 percent) and of workers in those firms covered by their employers' plans (62 percent) remain statistically unchanged from 2016.


Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.
There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.


Warming temperatures and smaller body sizes: synchronous changes in growth of North Sea fishes.
Decreasing body size has been proposed as a universal response to increasing temperatures. The physiology behind the response is well established for ectotherms inhabiting aquatic environments: as higher temperatures decrease the aerobic capacity, individuals with smaller body sizes have a reduced risk of oxygen deprivation. However, empirical evidence of this response at the scale of communities and ecosystems is lacking for marine fish species. Here, we show that over a 40-year period six of eight commercial fish species in the North Sea examined underwent concomitant reductions in asymptotic body size with the synchronous component of the total variability coinciding with a 1-2 °C increase in water temperature. Smaller body sizes decreased the yield-per-recruit of these stocks by an average of 23%. Although it is not possible to ascribe these phenotypic changes unequivocally to temperature, four aspects support this interpretation: (i) the synchronous trend was detected across species varying in their life history and life style; (ii) the decrease coincided with the period of increasing temperature; (iii) the direction of the phenotypic change is consistent with physiological knowledge; and (iv) no cross-species synchrony was detected in other species-specific factors potentially impacting growth. Our findings support a recent model-derived prediction that fish size will shrink in response to climate-induced changes in temperature and oxygen. The smaller body sizes being projected for the future are already detectable in the North Sea.


Rapid real-time recirculating PCR using localized surface plasmon resonance (LSPR) and piezo-electric pumping.
Rapid detection and characterization of pathogens in patients with bloodstream infections (BSIs) is a persistent problem for modern medicine, as current techniques are slow or provide incomplete diagnostic information. Real-time polymerase chain reaction (qPCR) allows specific detection of a wide range of targets and quantification of pathogenic burdens to aid in treatment planning. However, new technological advances are required for a rapid and multiplex implementation of qPCR in clinical applications. In this paper, the feasibility of a novel microfluidic platform for qPCR is presented, integrating highly sensitive, label-free localized surface plasmon resonance (LSPR) imaging of DNA hybridization into a recirculating chip design for real-time analysis. Single target and multiplex detection of DNA target amplification are demonstrated, with a limit of detection of 5 fg μL-1 of E. coli DNA for single target PCR, correlating with approximately 300 bacteria per mL. The results of this study demonstrate the potential of this platform for simultaneous real-time detection of multiple target genes within 15 minutes that could provide live saving benefits in patients with BSIs.