Failure of protein to improve time trial performance when added to a sports drink.
Recent studies have reported that adding approximately 2% protein to a carbohydrate sports drink increased cycle endurance capacity compared with carbohydrate alone. However, the practical implications of these studies work are hampered by the following limitations: (a) the rate of carbohydrate ingestion was less than what is considered optimal for endurance performance, and (b) the performance test (exercise time to fatigue) did not mimic the way in which athletes typically compete (i.e., a race in which a fixed distance or set amount of work is performed as quickly as possible). We tested the hypothesis that adding 2% protein to a 6% carbohydrate drink (CHO-PRO) would improve 80-km cycling time trial performance, as compared with a 6% carbohydrate drink (CHO) and a nonenergetic sweetened placebo (PLAC). Ten trained male cyclists (24 +/- 2 yr; VO2peak = 63 +/- 2 mL.kg(-1).min(-1); mean +/- SE) performed an 80-km laboratory time trial (TT) on three occasions separated by 7 d. In a double-blind crossover manner, subjects ingested CHO-PRO, CHO, or PLAC at a rate of 250 mL every 15 min with no temporal, verbal, or physiological feedback. Time to complete the TT was 4.4% lower (P < 0.002) during CHO (135 +/- 9 min) and CHO-PRO (135 +/- 9) compared with PLAC (141 +/- 10), with no difference between CHO and CHO-PRO (P = 0.92). Ingesting 6% carbohydrate at a rate of 1 L.h(-1) (60 g.h(-1)) improved an 80-km TT performance in trained male cyclists. However, adding 2% protein to a 6% carbohydrate drink provided no additional performance benefit during a task that closely simulated the manner in which athletes typically compete.


The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry.
Depressive episodes as reversible mental states are likely to be associated with equally reversible brain states. These can be examined with a variety of functional imaging methods using repeated measures designs. Studies using such an approach are reviewed. Changes in medial frontal, and in particular, cingulate cortex are reported in a majority of studies. Similarities and differences between different study results are discussed on the background of the functional neuroanatomy of the anterior cingulate, taking into account a variety of neurotransmitter systems. It is concluded that neuroimaging techniques are starting to equip us to conceptualize functional changes in the limbic loop containing the anterior cingulate as the common denominator of change and therapy effects in depressive states.


Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index.
The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.


A Novel Electrocardiographic Sign of an ST-Segment Elevation Myocardial Infarction-Equivalent: De Winter Syndrome.
Patients with de Winter syndrome, also termed anterior ST-segment elevation myocardial infarction (STEMI)-equivalent, represent 2% of all patients with acute anterior myocardial infarctions admitted to emergency departments (EDs). STEMI-equivalents do not present with classical electrocardiogram (ECG) changes but exhibit a critical stenosis of the left anterior descending (LAD) coronary artery. This is under-recognized by clinicians and is therefore associated with high morbidity and mortality. Here, we report a rare case of a novel, typical, STEMI-equivalent ECG pattern without obvious ST-segment elevation in a 34-year-old female who presented to our ED with substantial chest pain and a large, acute, transmural anterior myocardial infarction caused by acute occlusion of the LAD coronary artery. However, she presented as a non-STEMI case. A definite diagnosis of de Winter syndrome was made on the basis of clinical and ECG findings.


Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin.
The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies.


North American West Nile virus genotype isolates demonstrate differential replicative capacities in response to temperature.
The presence of West Nile virus (WNV) was first documented in California, USA, during the summer of 2003, and subsequently the virus has become endemic throughout the state. Sequence analysis has demonstrated that the circulating strains are representative of the North American (WN02) genotype that has displaced the East Coast genotype (NY99). A recent study has indicated that enhanced vector competence at elevated temperatures may have played a role in the displacement of the East Coast genotype by WN02. In the current study, four WN02 strains from California, including an initial 2003 isolate (COAV997), were compared to strain NY99 in growth curve assays in mosquito and duck embryonic fibroblast (DEF) cell lines at differing, biologically relevant temperatures to assess the relative temperature sensitivities of these natural isolates. COAV997 was significantly debilitated in viral replication in DEF cells at 44 °C. Full-length sequence comparison of COAV997 against the NY99 reference strain revealed non-synonymous mutations in the envelope glycoprotein (V159A), non-structural protein 1 (NS1) (K110N) and non-structural protein 4A (NS4A) (F92L), as well as two mutations in the 3' UTR: C→T at nt 10 772 and A→G at nt 10 851. These non-synonymous mutations were introduced into the NY99 viral backbone by site-directed mutagenesis. A mutant containing the NS1-K110N and NS4A-F92L mutations exhibited a debilitated growth phenotype in DEF cells at 44 °C, similar to that of COAV997. One explanation for the subsistence of this genotype is that COAV997 was obtained from an area of California where avian host species might not present elevated temperatures. These data indicate that the NS1 and NS4A mutations identified in some WN02 isolates could reduce thermal stability and impede replication of virus at temperatures observed in febrile avian hosts.


Cancer genetic predisposition: information needs of patients irrespective of risk level.
Increased insight into the information needs of people about cancer genetic predisposition could allow materials to be developed to improve decision-making for those at high risk, whilst those at lower risk could have their anxiety reduced without the need for referral to genetics services. This study aimed to identify information needs of patients concerned about a genetic predisposition to cancer, and explore how this varied according to risk perception, cancer worry, personal motivation and demographics. Stage 1 used semi-structured telephone interviews pre and post participants' genetic risk assessment. The findings informed stage two, a structured questionnaire survey of 1,112 patients, pre and post their genetic risk assessment. Participants were stratified by risk level and included those concerned about an inherited predisposition to breast, ovarian or colorectal cancer. About 512 (46%) responded with equal proportions of responders and non-responders across the risk categories. Findings indicated that irrespective of a person's actual or perceived level of risk, cancer worry, demographic background or personal motivation; priorities in the type of information required were similar. Greatest emphasis focused on information provision about how risk was assessed. Least important was acquiring an understanding about genes and inheritance patterns. Most participants reported difficulties accessing or finding information. Peoples' information needs are consistent irrespective of their risk level and therefore generalised information packages could be developed for anyone requesting cancer genetic risk assessment. Better information is likely to assist patients' understanding and ultimately increase concordance with recommended screening and preventative measures.


Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study.
It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400mum from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.


Empiric antibiotics for an elevated prostate-specific antigen (PSA) level: a randomised, prospective, controlled multi-institutional trial.
To determine the impact of empiric antibiotics on men with an elevated prostate-specific antigen (PSA) level. Men of any age with a PSA level of >2.5 ng/mL and normal digital rectal examination undergoing their first prostate biopsy were recruited from five medical centres. Patients with previous biopsy, prostate cancer, urinary tract infection (UTI) or prostatitis within the prior year, antibiotic use within 1 month, 5α-reductase inhibitor use, allergy to fluoroquinolones or clinical suspicion of UTI were excluded. Men were randomised to 2 weeks of ciprofloxacin or no antibiotic. A PSA measurement was obtained 21-45 days after randomisation immediately before prostate biopsy. The primary endpoint was the change in PSA level between baseline and immediately before biopsy. Complete data were available for 77 men with a mean (interquartile range) age of 60.6 (53-66) years. In the control group of men not receiving antibiotic (39 men), the mean baseline and pre-biopsy PSA levels were 6.5 and 6.9 ng/mL, respectively (P = 0.8). In men receiving ciprofloxacin (38 men), the mean baseline PSA level was 7.6 ng/mL and after 2 weeks of ciprofloxacin was 8.5 ng/mL (P = 0.7). Compared with controls not receiving antibiotic, use of ciprofloxacin was not associated with a statistically significant change in PSA level (P = 0.33). Prostate cancer was detected in 36 (47%) men, 23 (59%) in the control group and 13 (34%) in the antibiotic group (P = 0.04). Detection rates were not significantly associated with the change in PSA level between baseline and biopsy. The primary limitation of the study is early stoppage due to an interim futility analysis and poor accrual. Despite not meeting the target accrual goal, empiric use of antibiotics for asymptomatic men with an elevated PSA level does not appear to be of clinical benefit.


Internal nasal dilator in patients with obstructive sleep apnea.
The nasal valve area has the minimal cross-sectional area of the upper airways. Obstructive sleep apnea (OSA) is a common disorder. It has been reported that nasal obstruction may be associated with OSA. The aim of this study was to investigate whether the use an internal nasal dilator may be able to affect respiratory pattern in a group of patients with OSA. The use of internal nasal dilator was able to significantly reduce two relevant respiratory outcomes, such as the apnea-hypopnea index and the oxygen desaturation index, notably there was also a positive trend for the reduction of total sleep time with HbO2 <90%). Nas-air® was also able to significantly improve restorative sleep performance. In conclusion, the present study demonstrates that Nas-air® is a new internal nasal dilator potentially capable to significantly improve respiratory outcomes and sleep quality.


Redescription of three ektaphelenchus species (nematoda: aphelenchina).
Three Ektaphelenchus species with unusual spicules are redescribed. Ektaphelenchus obtusus and E. riograndensis are redescribed from newly discovered material in the collection of the USDA Forest Service RMRS. Lectotype slides are designated for both species. Ektaphelenchus obtusus is characterized by a set-off head, lips of unequal size, double rows of oocytes and spermatocytes, and a hooked spicule terminus. Ektaphelenchus riograndensis is distinguished by a rounded head with six equal lips, and spicules with a large, rounded apex, and recurved terminus. A bursa and gubernaculum are absent in both species. Ektaphelenchus scolyti is redescribed from type material deposited in the collection of Rothamsted Experimental Station. It is characterized by a well set-off head, double rows of oocytes and spermatocytes, and spicules with a hooked terminus. A bursa and gubernaculum are absent.


The role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release--II NAN-190 and SDZ 216-525.
Novel 5-HT1A receptor antagonists, WAY 100135 and WAY 100635, were used to test the involvement of 5-HT1A receptors in the decrease of hippocampal extracellular 5-HT induced by the 5-HT1A/alpha 1 ligands, NAN-190 and SDZ 216-525. Using microdialysis in anaesthetized rats, it was found that WAY 100135 (3 mg/kg s.c.) and WAY 100635 (0.3 mg/kg s.c.) antagonised the decrease of 5-HT induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.025 mg/kg s.c.) but did not alter 5-HT when administered alone. Both NAN-190 (0.03 and 0.3 mg/kg s.c.) and SDZ 216-525 (1 mg/kg s.c.) decreased 5-HT. The effect of 0.03 mg/kg s.c. NAN-190 was antagonised by WAY 100135 (3 mg/kg s.c.) and WAY 100635 (0.3 mg/kg s.c.). The effect of SDZ 216-525 (1 mg/kg s.c.) was also blocked by WAY 100635 (0.3 mg/kg s.c.). However, the 5-HT response to a high dose of NAN-190 (0.3 mg/kg s.c.) was not antagonised by WAY 100635 (0.3 or 3 mg/kg s.c.). Our experiments using WAY 100635 and WAY 100135 provide clear evidence that NAN-190 and SDZ 216-525 act as agonists at the 5-HT1A autoreceptor, supporting our earlier studies using the non-selective 5-HT1A antagonist, pindolol. However, our data reveal that, at least in the case of NAN-190, non-5-HT1A receptor mechanisms mediate the decrease of 5-HT induced by higher doses. A lack of specificity of NAN-190 (and possibly SDZ 216-525) at high doses may explain the failure of previous studies to detect a 5-HT1A receptor agonist action.


A long-term look at "early starters": Predicting adult psychosocial outcomes from childhood conduct problem trajectories.
Current evidence suggests that multiple pathways of "early-starting" conduct problems exist, including persisting and declining trajectories. Since relatively little is known about the early onset-declining pathway, this study examined the long-term outcomes of different childhood conduct problem trajectories in a disproportionately high-risk sample (N = 754). Parents reported on children's conduct problems at six time points (kindergarten to grade 7). At age 25, psychosocial outcomes were assessed across five domains (psychopathology, substance use, risky sexual behavior, antisocial behavior, and adaptive outcomes). Four childhood conduct problem trajectories were identified: extremely high increasing (EHI; 3.7%), high stable (HS; 22.0%), moderate decreasing (MD; 38.8%), and low decreasing (LD; 35.5%). The EHI and HS groups displayed the poorest psychosocial functioning at age 25, whereas the LD group exhibited the most positive adjustment. Although individuals in the MD group displayed relatively positive adjustment on some outcomes, they displayed more psychopathology and lower well-being in adulthood than the LD group. These findings suggest that there are diverse pathways of early-starting conduct problems, and that all early starters are at risk for later maladjustment. However, the degree and type of risk is related to the severity of conduct problems throughout childhood.


Social inequalities in low birth weight in England and Wales: trends and implications for future population health.
To examine social inequalities and trends in low birth weight in England and Wales. Analysis of routine birth data, comparing (a) couple and sole registered births, and (b) manual and non-manual occupational groups. England and Wales, 1993-2000. Social inequalities in low birth weight were evident throughout 1993-2000: relative to the non-manual group, there is an increased risk for the manual group (range in RR 1.22-1.35) and sole registrations (RR 1.51-1.67). An estimated 6.5% (2979 births) of low birth weight in 2000 could have been avoided if risks associated with the manual group were absent, and 2.8% (1290 births) avoided if risks associated with sole registration were absent. Between 1993 and 2000, the low birthweight rate increased significantly with an estimated overall increase of 11%. Increases were evident in all social groups (15% in manual, 11% in sole registrations and 9% in non-manual); however relative to non-manual the increase in RRs were not statistically significant for manual or sole registrations. When multiple births are excluded, the rate of low birth weight is reduced but there is still a significant increase over time and social differentials are undiminished. There are social inequalities in low birth weight in England and Wales that have not narrowed over an eight year period, 1993-2000. These inequalities are likely to affect childhood and adult health inequalities in the future, hence strategies will need to address differences in low birth weight and further monitoring of trends is therefore desirable.


The role of readily available clinical, laboratory and radiologic findings in distinguishing a/H1N1/2009 influenza from other causes of acute febrile respiratory illness under pandemic conditions.
During an influenza pandemic, clinicians need easily available clinical and laboratory criteria to distinguish influenza from similar respiratory illnesses. We compared A/H1N1/2009-polymerase chain reaction (PCR)-positive and matched PCR-negative hospitalized patients with suspected H1N1 influenza to identify factors that could assist physicians at patient admission. To identify factors significantly associated with A/ H1N1/2009 infection. A group of 145 patients with PCR-confirmed A/H1N1 2009 influenza admitted between 27 May 2009 and 3 December 2009 was matched with 145 PCR-negative patients by age, epidemiological week and pregnancy status. Epidemiological and clinical parameters and radiological findings on initial chest X-ray were compared between the two groups. Asthma (PCR+ 26%, PCR- 12%, P = 0.006) and military service (PCR+ 13%, PCR- 4%, P = 0.15) were associated with PCR-positive status in non-pregnant patients. At presentation, fever, cough, myalgia and fulfilling the pandemic influenza case definition were significantly more frequent in nonpregnant PCR+ patients (62/90/43/59% in PCR+ versus 38/69/30/35% in PCR-). In pregnant patients, fever and fulfilling the case definition were significantly associated with PCR-positive status. Mean leukocyte and absolute lymphocyte counts were significantly lower in both pregnant and nonpregnant PCR-positive patients. Significantly more PCR-negative non-pregnant patients (43% vs. 22% PCR+, P = 0.004) had abnormal chest X-ray (CXR) findings on presentation. In PCR-positive patients, patchy consolidation and interstitial infiltrates were the most common abnormalities. Under the conditions generated by the A/ H1 1/2009 pandemic, radiological findings did not distinguish reliably between influenza and other febrile respiratory illnesses. Asthma, military service, the pandemic case definition (particularly fever, cough and myalgia)


Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study.
There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6-7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0-151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3-23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0-112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.


The dynamics of food, alcohol and cigarette consumption in Russia during transition.
This paper presents evidence on the impact of individual as well as regional characteristics on the dynamics of fat, protein, alcohol and cigarette consumption, and on the diversity of the diet in Russia between 1994 and 2005. All those aspects of nutritional behavior are important inputs to the production of health. A dynamic panel data model is used to estimate demand functions for fat, protein, alcohol, cigarettes and diversity of the diet. The results suggest the existence of strong habits in drinking and smoking, and the absence of habits in fat and protein consumption. We also found evidence of habit formation for food diversity. Comparing nutritional behavior of younger and older consumers, we find significant differences in the demand for fat and cigarettes. Older consumers seem to be more persistent in their drinking and smoking behavior. Similarly, men show higher habit persistence for alcohol and cigarette consumption. The results also suggest that among individual determinants, especially education, income and employment have statistically significant impacts on consumption behavior. Regarding the macroeconomic variables, economic growth is negatively related to protein consumption, while regional unemployment rate is negatively affecting the demand for protein and food diversity. Finally, Russian consumers react to the price changes of alcohol, cigarettes, fat and protein as suggested by theory. Consumer demand for food diversity responds negatively to price changes of alcohol and cigarettes, but positively to the price of fat.


Danger signals and inflammaging in osteoarthritis.
Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease. Long considered to be a "wear and tear" disease, OA is now seen as a low-grade inflammation disease that affects all tissues of the joint, involving cartilage degradation, bone remodelling, osteophytes, and synovitis. The process, called inflammaging, is characterised by the association of low-grade inflammation, profound changes in intra-cellular mechanisms, and the decreased efficiency of the immune system with ageing. The activation of innate immunity plays a critical role in the development and progression of OA. Innate immunity, including inflammasome activation, is triggered by small endogenous molecules called alarmins or damage-associated molecular patterns (DAMPs). These molecules are released in the extracellular media after cell stress or damage, bind to pathogen-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), and activate the secretion of pro-inflammatory factors, leading to joint inflammation. Moreover, such sterile inflammation triggers cell senescence, characterised by a senescence-associated secretory phenotype (SASP). Understanding the substantial age-related changes of joint tissues that influence the pathogenesis of OA is critical to improving the quality of life of elderly people in the context of increased life expectancy. This review will focus on age-related sterile inflammation in OA and highlight the various innovative and promising therapies targeting the mechanisms of aging.


An assessment of pain management among patients presenting to emergency medical services after suffering a fall.
Emergency Medical Services (EMS) professionals frequently care for patients experiencing acute pain. Analgesics are critical in patient comfort and satisfaction levels during the treatment of acute pain. The objective of this study was to assess the frequency of pain management in patients suffering a fall, the documented pain score, and the location of their injuries. It was hypothesized that the frequency of analgesia administration was low and would be associated with injury location. This was a retrospective review of patients presenting with a complaint of an injury from a fall transported by a single municipal EMS system. Administration of analgesia was the primary outcome variable, with pain severity, injury location, age, gender, race, and distance of fall the independent variables of interest. Pain severity was assessed using a 0-10 scale. Injury location was defined as head/neck, extremities, back, and hip. Patients were deemed ineligible for analgesia, according to local protocol, if they reported chest or abdominal pain, or were hemodynamically unstable as determined by an assessment of pulse and blood pressure. There were 1,200 patients who were classified as having injuries suffered from a fall, with 76 (6.3%) ineligible for analgesia. Ninety-two (8.2%) patients received analgesia, and they had a mean recorded pain score of 9.1 (95% CI, 8.7-9.5), which was higher than those who did not receive analgesia (5.8; 95% CI, 5.5-6.2). Analgesia administration was associated with injury location; patients experiencing an extremity injury (OR = 13.23; 95% CI, 5.58-31.36; P < .001) or hip injury (OR = 11.65; 95% CI, 4.64-29.24; P < .001) had increased odds of analgesia administration compared to those with head/neck injury. The odds of analgesia administration were decreased for black patients (OR = 0.19; 95% CI, 0.08-0.44; P < .001) when compared to white patients. Analgesia administration was provided to 10% of eligible patients, and was associated with injury location. Of concern was the number of patients who suffered a fall and did not receive a documented pain score. The results from this study indicated a need for education relating to pain management in patients suffering a fall.


Sedation and regional anaesthesia in the adult patient.
This review discusses sedation for regional anaesthesia in the adult population. The first section deals with general aspects of sedation and shows that the majority of patients receiving sedation for regional anaesthesia are satisfied and would choose it again. Methods of assessing the level of sedation are discussed with emphasis on clinical measures. The pharmacology of the drugs involved in sedation is discussed, with propofol and remifentanil appearing to be the combination of choice for sedation in regional anaesthesia. The techniques for administering sedation are discussed and replacement of the traditional repeated boluses or continuous infusion with pharmacokinetic and patient-controlled systems is supported. Patient satisfaction studies suggest that patient-controlled systems are preferred.


Analysing Friedel averages and differences.
Various practical applications of the average (A) and difference (D) of Friedel opposites are described. Techniques based on the resonant-scattering contribution to Friedel differences are applied to see whether a crystal is centrosymmetric or not, and to determine the point group of the crystal. For the validation of a structural study, plots of A(obs) against A(model), and D(obs) against D(model) are used extensively. Moreover, it is useful to display both plots on the same graph. Intensity measurements on a crystal of NaClO(3) were made at three different speeds, with two different radiations and two different diffractometers, and treated with two different software packages and four different absorption corrections. The evaluation of these numerous data sets reveals underlying deficiencies. For comparison, plots of A(obs) against A(model), and D(obs) against D(model) are presented for two centrosymmetric crystals.


Cell type-specific expression of SEPT3-homology subgroup members controls the subunit number of heteromeric septin complexes.
Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer and heterooctamer complexes, which serve as building blocks for apolar filamentous structures that differ among cell types. To determine how tissue-specific septin paralogue expression may shape core heteromer repertoires and thereby modulate properties of septin filaments, we devised protocols to analyze native septin heteromers with distinct numbers of subunits. Our evidence based on genetically manipulated human cells supports and extends recent concepts of homology subgroup-restricted assembly into distinct categories of apolar heterohexamers and heterooctamers. We also identify a category of tetramers that have a subunit composition equivalent to an octameric building block. These atypical tetramers are prevalent in lymphocytes and neural tissues, in which octamers are abundant but hexamers are rare. Our results can be explained by tissue-specific expression of SEPT3 subgroup members: SEPT3, SEPT9, and SEPT12. These serve as cognate subunits in either heterooctamers or atypical tetramers but exhibit different preferences in various tissues. The identified tissue-specific repertoires of septin heteromers provide insights into how higher-order septin structures with differential properties and stabilities may form in diverse animal cell types.


Personalised genetic intervention for Duchenne muscular dystrophy: antisense oligomers and exon skipping.
Duchenne muscular dystrophy (DMD) arises from protein-truncating mutations in the large dystrophin gene that preclude synthesis of a functional protein that primarily stabilizes muscle fibre membranes. The absence of dystrophin leads to this most common and serious form of childhood muscle-wasting. Since the identification of the dystrophin gene in 1987, cell and gene repair or replacement therapies have been evaluated for DMD treatment and one genetic intervention, exon skipping, is now in clinical trials. Antisense oligomers have been designed to redirect dystrophin splicing patterns so that targeted exons may be removed from a defective dystrophin pre-mRNA to either restore the reading frame of a deletion, or excise an in-frame exon corrupted by a nonsense mutation or micro-insertion/deletion. This review discusses the evolution of oligomer induced exon skipping, including in vitro applications, evaluation of different oligomer chemistries, the treatment of animal models and alternative exon skipping strategies involving viral expression cassettes and ex vivo manipulation of stem cells. The discussion culminates with the current clinical trials and the great challenges that lie ahead. The major obstacle to the implementation of personalised genetic treatments to address the many different mutations that can lead to DMD, are considered to be establishing effective treatments for the different patients and their mutations. Furthermore, the view of regulatory authorities in assessing preclinical data on potentially scores of different but class-specific compounds will be of paramount importance in expediting the clinical application of exon skipping therapy for this serious and relentlessly progressive muscle wasting disease.


Tree-average distances on certain phylogenetic networks have their weights uniquely determined.
A phylogenetic network N has vertices corresponding to species and arcs corresponding to direct genetic inheritance from the species at the tail to the species at the head. Measurements of DNA are often made on species in the leaf set, and one seeks to infer properties of the network, possibly including the graph itself. In the case of phylogenetic trees, distances between extant species are frequently used to infer the phylogenetic trees by methods such as neighbor-joining. This paper proposes a tree-average distance for networks more general than trees. The notion requires a weight on each arc measuring the genetic change along the arc. For each displayed tree the distance between two leaves is the sum of the weights along the path joining them. At a hybrid vertex, each character is inherited from one of its parents. We will assume that for each hybrid there is a probability that the inheritance of a character is from a specified parent. Assume that the inheritance events at different hybrids are independent. Then for each displayed tree there will be a probability that the inheritance of a given character follows the tree; this probability may be interpreted as the probability of the tree. The tree-average distance between the leaves is defined to be the expected value of their distance in the displayed trees. For a class of rooted networks that includes rooted trees, it is shown that the weights and the probabilities at each hybrid vertex can be calculated given the network and the tree-average distances between the leaves. Hence these weights and probabilities are uniquely determined. The hypotheses on the networks include that hybrid vertices have indegree exactly 2 and that vertices that are not leaves have a tree-child.


Targeted inhibition of the WEE1 kinase as a novel therapeutic strategy in neuroendocrine neoplasms.
Neuroendocrine neoplasms (NENs) represent a rare and heterogeneous group of malignancies, sharing features of both neural and endocrine cells. NENs G3 appear as a highly aggressive subset with a poor prognosis and limited therapeutic options. The small-molecule inhibitor of the WEE1 tyrosine kinase, adavosertib (AZD1775), has previously demonstrated potent anti-tumor effects on various types of cancer in preclinical and clinical studies. However, the role of adavosertib in NENs G3 had remained elusive. We evaluated the effects of adavosertib on pancreatic (BON-1, QGP-1) and bronchopulmonary (NCI-H720) neuroendocrine tumor cell lines applying 2D and 3D spheroid models. We newly demonstrated that adavosertib is sufficient to reduce cell viability and proliferation in neuroendocrine cell lines with features of high-grade NENs. As underlying mechanisms, we identified adavosertib-mediated DNA double-strand breaks and a G2/M cell cycle checkpoint abrogation leading into mitotic catastrophe and cancer cell apoptosis. Silencing of WEE1 via siRNA transfection resulted in a phenotype similar to adavosertib treatment. Together, inhibition of the WEE1 tyrosine kinase applying adavosertib on NENs G3 outlines a promising novel therapeutic strategy.


Use of Daphnia spp. for the ecotoxicological assessment of water quality in an agricultural watershed in South-Central Chile.
Because of the importance of surface waters from the Chillán River watershed (Chile) for recreation, agricultural irrigation, and the production of drinking water, local concern about river water quality has increased considerably during the last decade. Agricultural and forestry activities in the watershed, characterized by an intensive use of pesticides, are thought to play an important role in the generation of non-point-source pollution, whereas the discharge of urban wastewater from the city of Chillán constitutes a major point source of pollution. In the present investigation, acute and chronic laboratory bioassays using Daphnia spp. were conducted on surface water samples from 17 river stations located throughout the watershed. Sampling occurred on 6 occasions during a 16-month period (2000 to 2001) and included both high and low flow conditions. Almost all toxic effects observed in summer were directly related to the discharge of urban wastewater, whereas toxicity in rural areas was mainly detected during the winter period when rainfall and river flow are high. Toxicity test results were compared with measured physicochemical water-quality data. Mortality and alterations in reproductive success of Daphnia spp. were not consistently reflected in detected chemical pollution. With only one exception (atrazine), detected pesticide concentrations were below known toxicity levels. However, additive and synergistic effects of the presence of a mixture of pesticides could not be excluded as a possible cause of observed toxicity. At several stations, filtering of the water sample led to a strong decrease in toxicity, which suggests the presence of xenobiotics attached to the smaller sediment fraction. Inclusion of sediment chemical analysis and sediment toxicity testing in future work should therefore be encouraged. The presented approach provided information about the adverse effects of human activities on surface water quality in the watershed, not easily obtained from classical monitoring schemes. In specific cases, the approach may represent an economically attractive alternative to physicochemical analyses. Modifications to the proposed methodology should be introduced if the effects of intrastorm and interstorm variability of water quality are to be analyzed.


Sensory and motor differences in Autism Spectrum Conditions and developmental coordination disorder in children: A cross-syndrome study.
Recent research has shown that Developmental coordination disorder (DCD) can present with some similar symptomology as Autism Spectrum Conditions (ASC). This paper therefore explored the similarities and differences in coordination and sensory responsivity between DCD and ASC. 77 children took part: 42 (35 male, 7 female) with ASC (ages 7-21: mean age 12.23 years), 26 (19 male, 7 female) with DCD (ages 7-21; mean age 11.07 years) and 9 (2 male, 7 female) with ASC and DCD (ages 8-15; mean age 12.27). All groups completed a battery of validated parent report measures online that included motor coordination (DCDQ), sensory responsivity (SPC-R) and social communication measures (AQ). Results showed no significant differences in coordination, and some significant differences in sensory responsivity between ASC and DCD (increased visual and auditory responsivity and decreased proprioception). Exploratory analysis showed that these differences showed good validity in identifying the diagnosis of ASC and DCD. These results elucidate the underlying causes of motor coordination difficulties in both conditions. Specifically, ASC coordination difficulties appear linked to visual processing impairments, whilst DCD coordination difficulties appear to be linked to spatial processing. This may aid better diagnosis and intervention for these conditions.


Modesty and recognition--a qualitative study of the lived experience of recovery from anal cancer.
Anal cancer is a rare disease within the cancer spectrum. Long-term disabilities are notable and place increased demands on rehabilitation. The objective of this study was to describe the lived experiences of recovery from anal cancer, including which and how resources may help survivors of anal cancer to resist and to manage potentially complex stressors encountered in the recovery from the disease. A qualitative, salutogenetic-oriented, phenomenological study was conducted based on audio-taped, semi-structured interviews. Interviewee selection was carried out through purposeful sampling. Sixteen individuals (11 women and five men; average age 52 years), who had completed therapy for anal cancer (average 31 months ago), participated in the study. Transcripts from the audio-taped interviews were used for qualitative text condensation analysis, inspired by Giorgi's phenomenological methodology. The analysis revealed two concepts, modesty and recognition, which describe the essence of the lived experience of anal cancer, and which each appear to be important resistance resources. While modesty is regarded as an enforced and necessary competence developed and mastered by the individual, recognition refers to a desired, but often lacking, resource in the individual's interaction with health authorities and relatives. Anal cancer appears to lack attention and deserved recognition from professional and social services, which in itself may lead to mistrust and devaluation of the individual seeking support. It is recommended that both researchers and rehabilitation services incorporate, prioritize, and advise on the disease's specific issues and the terms under which the survivor can maintain an active, working and social life, as desired.


Establishing an anemia clinic for optimal erythropoietic-stimulating agent use in hematology-oncology patients.
Erythropoietic-stimulating agent (ESA) therapy has significantly impacted the management of chemotherapy-induced anemia (CIA) by decreasing the number of red blood cell transfusions required by patients with cancer. However, managing these patients with ESA therapy has become increasingly difficult since the release of the Centers for Medicare & Medicaid Services' new National Coverage Determination document because of the disparities between this document and recommendations from expert-reviewed national clinical guidelines on the treatment of anemia. This article describes a collaborative practice agreement between pharmacists and physicians as one approach to managing CIA in hematology-oncology patients in an anemia clinic. The goal of the pharmacist-managed anemia clinic is to improve patient satisfaction and clinical outcomes associated with the treatment of CIA. This article describes the rationale for the clinic and discusses its design and implementation in managing ESA, iron, folate, and vitamin B12 therapy for CIA in hematology-oncology patients. The pharmacist's role is justified in this clinic model through increased adherence to evidence-based practice guidelines and decreased costs associated with ESA therapy.


An oxygenase-independent cholesterol catabolic pathway operates under oxic conditions.
Cholesterol is one of the most ubiquitous compounds in nature. The 9,10-seco-pathway for the aerobic degradation of cholesterol was established thirty years ago. This pathway is characterized by the extensive use of oxygen and oxygenases for substrate activation and ring fission. The classical pathway was the only catabolic pathway adopted by all studies on cholesterol-degrading bacteria. Sterolibacterium denitrificans can degrade cholesterol regardless of the presence of oxygen. Here, we aerobically grew the model organism with (13)C-labeled cholesterol, and substrate consumption and intermediate production were monitored over time. Based on the detected (13)C-labeled intermediates, this study proposes an alternative cholesterol catabolic pathway. This alternative pathway differs from the classical 9,10-seco-pathway in numerous important aspects. First, substrate activation proceeds through anaerobic C-25 hydroxylation and subsequent isomerization to form 26-hydroxycholest-4-en-3-one. Second, after the side chain degradation, the resulting androgen intermediate is activated by adding water to the C-1/C-2 double bond. Third, the cleavage of the core ring structure starts at the A-ring via a hydrolytic mechanism. The (18)O-incorporation experiments confirmed that water is the sole oxygen donor in this catabolic pathway.


Efficacy of a weight loss program prior to robot assisted radical prostatectomy in overweight and obese men with prostate cancer.
Obesity in prostate cancer patients is associated with poor prostate-cancer specific outcomes. Exercise and nutrition can reduce fat mass; however, few studies have explored this as a combined pre-surgical intervention in clinical practice. This study examined the efficacy of a weight loss program for altering body composition in prostate cancer patients prior to robot assisted radical prostatectomy (RARP). A retrospective analysis of 43 overweight and obese prostate cancer patients, aged 47-80 years, who completed a very low-calorie diet (~3000-4000 kJ) combined with moderate-intensity exercise (90 min/day) prior to RARP. Whole body and regional fat mass (FM) and lean mass (LM) were assessed by dual-energy x-ray absorptiometry pre- and post-program. Body weight, waist circumference, and blood pressure were assessed weekly, with surgery-related adverse effects recorded at time of surgery and follow-up appointments. With a median of 29 days (IQR: 24-35days) on the program, patients significantly (p < 0.001) reduced weight (-7.3 ± 2.9 kg), FM (-5.0 ± 2.6 kg), percent body fat (-3.1 ± 2.5%), trunk FM (-3.4 ± 1.8 kg), LM (-2.4 ± 1.8 kg), and appendicular LM (-1.2 ± 1.0 kg). Lower weight, FM, percent FM, trunk FM, and visceral FM were associated with less surgery-related adverse effects (rs = 0.335 to 0.468, p < 0.010). Systolic and diastolic blood pressure were reduced (p < 0.001) by 15 ± 22 and 8 ± 10 mmHg, respectively over the weight loss intervention. Undertaking a combined low-calorie diet and exercise program for weight loss in preparation for RARP resulted in substantial reductions in FM, with improvements in blood pressure, that may benefit surgical outcomes.


GABA(B) receptors couple to potassium and calcium channels on identified lateral perforant pathway projection neurons.
Activation of presynaptic GABA(B) receptors inhibits neurotransmitter release at most cortical synapses, at least in part because of inhibition of voltage-gated calcium channels. One synapse where this is not the case is the lateral perforant pathway synapse onto dentate granule cells in the hippocampus. The current study was conducted to determine whether the neurons that make these synapses express GABA(B) receptors that can couple to ion channels. Perforant pathway projection neurons were labeled by injecting retrograde tracer into the dorsal hippocampus. The GABA(B) receptor agonist baclofen (10 microM) activated inwardly rectifying potassium channels and inhibited currents mediated by voltage-gated calcium channels in retrogradely labeled neurons in layer II of the lateral entorhinal cortex. These effects were reversed by coapplication of the selective GABA(B) receptor antagonist CGP 55845A (1 microM). Equivalent effects were produced by 100 microM adenosine, which inhibits neurotransmitter release at lateral perforant pathway synapses. The effects of baclofen and adenosine on inward currents were largely occlusive. These results suggest that the absence of GABA(B) receptor-mediated presynaptic inhibition at lateral perforant pathway synapses is not simply due to a failure to express these receptors and imply that GABA(B) receptors can either be selectively localized or regulated at terminal versus somatodendritic domains.


A Multilevel Tailored Web App-Based Intervention for Linking Young Men Who Have Sex With Men to Quality Care (Get Connected): Protocol for a Randomized Controlled Trial.
HIV epidemic among young men who have sex with men (YMSM) is characterized by strong racial disparities and concerns about the availability and access to culturally appropriate HIV prevention and care service delivery. Get Connected, a Web-based intervention that employs individual- and system-level tailoring technology to reduce barriers to HIV prevention care (eg, HIV or sexually transmitted infection [STI] testing, pre-exposure prophylaxis [PrEP]), was developed for YMSM (age 15-24 years). This protocol details the design and procedures of a 2-phase project that includes mystery shopping and a randomized controlled trial (RCT) to test the efficacy of Get Connected among YMSM in Philadelphia, Atlanta, and Houston. The objective of mystery shopping is to examine the quality of HIV test counseling and PrEP-related referrals for YMSM within local HIV or STI testing sites. The objective of the RCT is to test the efficacy of Get Connected for increasing HIV-negative or HIV-unknown YMSM's successful uptake of HIV prevention services (eg, routine HIV or STI testing), PrEP awareness, and likelihood to start PrEP (PrEP willingness), compared with those in the control condition, over a 12-month period. For Phase 1, we will create a master list of HIV and STI testing sites in each city. We will enroll and train 10-15 mystery shoppers per city; each testing site will be separately visited and assessed by 2 mystery shoppers. After each site visit, the mystery shoppers will complete a site evaluation to record their perceptions of various measures including lesbian, gay, bisexual, transgender, queer visibility and inclusivity, privacy and confidentiality, provider-patient interactions, and clinic environment. For Phase 2, we will enroll 480 YMSM for 12 months across the 3 iTech cities into a 2-arm prospective RCT. Participants randomized to the control condition are directed to the AIDSVu.org testing site locator. Participants randomized to the intervention condition will be granted access to a Web app with content tailored to their specific demographic characteristics (eg, age, race or ethnicity, location, and relationship status), HIV and STI risk behaviors (eg, HIV and STI testing history, substance use, communication with partners regarding status) and sociocultural context (eg, homelessness, incarceration). Study assessments will occur at enrollment and at 1, 3, 6, 9, and 12 months postenrollment. Get Connected research activities began in September 2016 and are ongoing. To date, institutional review board (IRB) submission is complete and IRB authorization agreements are pending at several other universities. The deployment of Get Connected through a mobile-optimized Web app seeks to optimize the intervention's acceptability, accessibility, availability, and long-term affordability among YMSM. ClinicalTrials.gov (NCT03132415); https://clinicaltrials.gov/ct2/show/NCT03132415 (Archived by WebCite at http://www.webcitation.org/70j4gSFbZ). RR1-10.2196/10444.


Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.


The impact of the FIFA 11+ training program on injury prevention in football players: a systematic review.
The FIFA 11+ is a simple, and easy to implement, sports injury prevention program comprising a warm up of 10 conditioning exercises. The aim of this systematic review was to evaluate the impact of the FIFA 11+ on injury incidence, compliance and cost effectiveness when implemented among football players. MEDLINE, EMBASE and Scopus databases were searched using the search terms "FIFA 11+", "football", "soccer", "injury prevention", and "The 11". The titles and abstracts were screened by two independent reviewers and the data were filtered by one reviewer using a standardized extraction form and thereafter checked by another one. The risk of bias and the methodological quality of the studies were evaluated through the PEDro score and Critical Appraisal Skills Programme (CASP). A total of 911 studies were identified, of which 12 met the inclusion criteria of the review. The FIFA 11+ has demonstrated how a simple exercise program completed as part of warm-up can decrease the incidence of injuries in amateur football players. In general, considerable reductions in the number of injured players, ranging between 30% and 70%, have been observed among the teams that implemented the FIFA 11+. In addition, players with high compliance to the FIFA 11+ program had an estimated risk reduction of all injuries by 35% and show significant improvements in components of neuromuscular and motor performance when participating in structured warm-up sessions at least 1.5 times/week. Most studies had high methodological quality and a low risk of bias. Given the large number of people who play football at amateur level and the detrimental impact of sports injuries on a personal and societal level, the FIFA 11+ can be considered as a fundamental tool to minimize the risks of participation in a sport with substantial health benefits.


Dual-channel low-coherence interferometry and its application to quantitative phase imaging of fingerprints.
We introduce an off-axis, wide-field, low-coherence and dual-channel interferometric imaging system, which is based on a simple-to-align, common-path interferometer. The system requires no optical-path-difference matching between the interferometric arms in order to obtain interference with low-coherence light source, and is capable of achieving two channels of off-axis interference with high spatial frequency. The two 180°-phase-shifted interferograms are acquired simultaneously using a single digital camera, and processed into a single, noise-reduced and DC-suppressed interferogram. We demonstrate using the proposed system for phase imaging of fingerprint templates. Due to the fact that conventional phase unwrapping algorithms cannot handle the complex and deep surface topography imposed by fingerprint templates, we experimentally implemented two-wavelength phase unwrapping using a supercontinuum laser coupled to acousto-optical tunable filter, together functioning as a low-coherence tunable light source. From the unwrapped phase map, we produced high quality depth profiles of fingerprint templates.


Adapting Semantic Natural Language Processing Technology to Address Information Overload in Influenza Epidemic Management.
Explosion of disaster health information results in information overload among response professionals. The objective of this project was to determine the feasibility of applying semantic natural language processing (NLP) technology to addressing this overload. The project characterizes concepts and relationships commonly used in disaster health-related documents on influenza pandemics, as the basis for adapting an existing semantic summarizer to the domain. Methods include human review and semantic NLP analysis of a set of relevant documents. This is followed by a pilot-test in which two information specialists use the adapted application for a realistic information seeking task. According to the results, the ontology of influenza epidemics management can be described via a manageable number of semantic relationships that involve concepts from a limited number of semantic types. Test users demonstrate several ways to engage with the application to obtain useful information. This suggests that existing semantic NLP algorithms can be adapted to support information summarization and visualization in influenza epidemics and other disaster health areas. However, additional research is needed in the areas of terminology development (as many relevant relationships and terms are not part of existing standardized vocabularies), NLP, and user interface design.


Developmental exposure of mice to dioxin promotes transgenerational testicular inflammation and an increased risk of preterm birth in unexposed mating partners.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse model, we previously found that adult female mice exposed in utero to TCDD (F1 generation) as well as multiple subsequent generations (F2-F4) exhibited reduced fertility and an increased incidence of spontaneous preterm birth. Additional studies revealed that male F1 mice with a similar in utero/developmental TCDD exposure also exhibited diminished fertility and conferred an increased risk of preterm birth to their unexposed mating partners. Herein, we extend these previous observations, reporting that reduced fertility in male F1 mice is linked to testicular inflammation which coincides with apoptosis of developing spermatocytes, sub-fertility and an increased risk of preterm birth in their unexposed mating partners. Significantly, in the absence of additional toxicant exposure, testicular inflammation and reduced fertility persisted in F2 and F3 males and their control mating partners also frequently exhibited spontaneous preterm birth. Although a steady, global decline in male fertility has been noted over the last few decades, the reasons for these changes have not been firmly established. Likewise, the PTB rate in the U.S. and other countries has paralleled industrial development, suggesting a possible relationship between environmental toxicant exposure and adverse pregnancy outcomes. Most current clinical strategies to prevent preterm birth are focused solely on the mother and have yielded limited benefits. In contrast, our studies strongly suggest that the preconception testicular health of the father is a critical determinant of pregnancy outcomes in mice. Future clinical studies should examine the potential contribution of the male to gestation length in women and whether efforts to reduce the incidence of preterm birth should be initiated in both parents prior to pregnancy.


Genetic variants in mRNA untranslated regions.
Genome Wide Association Studies (GWAS) have mapped thousands of genetic variants associated with complex disease risk and regulating quantitative traits, thus exploiting an unprecedented high-resolution genetic characterization of the human genome. A small fraction (3.7%) of the identified associations is located in untranslated regions (UTRs), and the molecular mechanism has been elucidated for few of them. Genetic variations at UTRs may modify regulatory elements affecting the interaction of the UTRs with proteins and microRNAs. The overall functional consequences include modulation of messenger RNA (mRNA) transcription, secondary structure, stability, localization, translation, and access to regulators like microRNAs (miRNAs) and RNA-binding proteins (RBPs). Alterations of these regulatory mechanisms are known to modify molecular pathways and cellular processes, potentially leading to disease processes. Here, we analyze some examples of genetic risk variants mapping in the UTR regulatory elements. We describe a recently identified genetic variant localized in the 3'UTR of the TNFSF13B gene, associated with autoimmunity risk and responsible of an increased stability and translation of TNFSF13B mRNA. We discuss how the correct use and interpretation of public GWAS repositories could lead to a better understanding of etiopathogenetic mechanisms and the generation of robust biological hypothesis as starting point for further functional studies. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Disease.


[Neuronal background two-P-domain potassium channels: molecular and functional aspects].
Background K+ conductances are a major determinant of membrane resting potential and input resistance, two key components of neuronal excitability. Background channels have been cloned and form a K+ channel family structurally different from Kv, KCa and Kir channels. These channels with 2P domains (K2P channels) are voltage- and time-independent. They are relatively insensitive to classical potassium channels blockers such as TEA, 4-AP, Ba2+ and Cs+. TASK and TREK subunits are widely expressed in the nervous system. Open at rest, these channels mainly contribute to the resting potential of somatic motoneurons, brainstem respiratory and chemoreceptor neurones, and cerebellar granule cells. K2P channels are regulated by numerous physical and chemical stimuli including extracellular and intracellular pH, temperature, hypoxia, pressure, bioactive lipids, and neurotransmitters. The regulation of these background K+ channels profoundly alters the neuronal excitability. For example, in Aplysia, regulation of a background potassium conductance by neurotransmitters is involved in synaptic modulation, a simple and primitive form of learning. The recent discovery that clinical compounds such as volatile anaesthetics and other neuroprotective agents including riluzole and unsaturated fatty acids activate K2P channels suggest that neuronal background K+ channels are attractive targets for the development of new drugs.


Translational research: bridging the gap between long-term weight loss maintenance research and practice.
The number of US adults classified as overweight or obese has dramatically increased in the past 25 years, resulting in a significant body of research addressing weight loss and weight loss maintenance. However, little is known about the potential of weight loss maintenance interventions to be translated into actual practice settings. Thus, the purpose of this article is to determine the translation potential of published weight loss maintenance intervention studies by determining the extent to which they report information across the reach, efficacy/effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. A secondary purpose is to provide recommendations for research based on these findings. To identify relevant research articles, a literature search was conducted using four databases; 19 weight loss maintenance intervention studies were identified for inclusion. Each article was evaluated using the RE-AIM Coding Sheet for Publications to determine the extent to which dimensions related to internal and external validity were reported. Approximately half of the articles provided information addressing three RE-AIM dimensions, yet only a quarter provided information addressing adoption and maintenance. Significant gaps were identified in understanding external validity, and metrics that could facilitate the translation of these interventions from research to practice are presented. Based upon this review, it is unknown how effective weight loss maintenance interventions could be in real-world situations, such as clinical or community practice settings. Future studies should be planned to address how weight loss maintenance intervention programs will be adopted and maintained, with special attention to costs for participants and for program implementation.


Designing the ideal model for assessment of wound contamination after gunshot injuries: a comparative experimental study.
Modern high-velocity projectiles produce temporary cavities and can thus cause extensive tissue destruction along the bullet path. It is still unclear whether gelatin blocks, which are used as a well-accepted tissue simulant, allow the effects of projectiles to be adequately investigated and how these effects are influenced by caliber size. Barium titanate particles were distributed throughout a test chamber for an assessment of wound contamination. We fired .22-caliber Magnum bullets first into gelatin blocks and then into porcine hind limbs placed behind the chamber. Two other types of bullets (.222-caliber bullets and 6.5 × 57 mm cartridges) were then shot into porcine hind limbs. Permanent and temporary wound cavities as well as the spatial distribution of barium titanate particles in relation to the bullet path were evaluated radiologically. A comparison of the gelatin blocks and hind limbs showed significant differences (p < 0.05) in the mean results for all parameters. There were significant differences between the bullets of different calibers in the depth to which barium titanate particles penetrated the porcine hind limbs. Almost no particles, however, were found at a penetration depth of 10 cm or more. By contrast, gas cavities were detected along the entire bullet path. Gelatin is only of limited value for evaluating the path of high-velocity projectiles and the contamination of wounds by exogenous particles. There is a direct relationship between the presence of gas cavities in the tissue along the bullet path and caliber size. These cavities, however, are only mildly contaminated by exogenous particles.


High-order modes of spoof surface plasmonic wave transmission on thin metal film structure.
Recently, conformal surface plasmon (CSP) structure has been successfully proposed that could support spoof surface plasmon polaritons (SPPs) on corrugated metallic strip with ultrathin thickness [Proc. Natl. Acad. Sci. U.S.A. 110, 40-45 (2013)]. Such concept provides a flexible, conformal, and ultrathin wave-guiding element, very promising for application of plasmonic devices, and circuits in the frequency ranging from microwave to mid-infrared. In this work, we investigated the dispersions and field patterns of high-order modes of spoof SPPs along CSP structure of thin metal film with corrugated edge of periodic array of grooves, and carried out direct measurement on the transmission spectrum of multi-band of surface wave propagation at microwave frequency. It is found that the mode number and mode bands are mainly determined by the depth of the grooves, providing a way to control the multi-band transmission spectrum. We have also experimentally verified the high-order mode spoof SPPs propagation on curved CSP structure with acceptable bending loss. The multi-band propagation of spoof surface wave is believed to be applicable for further design of novel planar devices such as filters, resonators, and couplers, and the concept can be extended to terahertz frequency range.


The relationship between headache and religious attendance (the Nord-Trøndelag health study-HUNT).
Religious belief can be used as a pain coping strategy. Our purpose was to evaluate the relationship between headache and religious activity using prospective data from a large population-based study. This longitudinal cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Survey (HUNT 2 and 3) performed in 1995-1997; and 2006-2008. Among the 51,383 participants aged ≥ 20 years who answered headache questions at baseline, 41,766 were eligible approximately 11 years later. Of these, 25,177 (60%) completed the question in HUNT 3 regarding religious activity. Frequent religious attendees (fRA) (used as a marker of stronger religious belief than average) were defined as those who had been to church/prayer house at least once monthly during the last six months. In the multivariate analyses, adjusting for known potential confounders, individuals with headache 1-14 days/month in HUNT 2 were more likely to be fRA 11 years later than headache-free individuals. Migraine at baseline predisposed more strongly to fRA at follow-up (OR = 1.25; 95% CI 1.19-1.40) than did non-migrainous headache (OR = 1.13; 95% 1.04-1.23). The odds of being fRA was 48% increased (OR 1.48; 95% 1.19-1.83) among those with migraine 7-14 days/month at baseline compared to subjects without headache. In contrast, headache status at baseline did not influence the odds of being frequent visitors of concerts, cinema and/or theatre at follow-up 11 years later. In this prospective study, headache, in particular migraine, at baseline slightly increased the odds of being fRA 11 years later.


No association of PTPN22 polymorphisms with susceptibility to ocular Behcet's disease in two Chinese Han populations.
Behcet's disease is known as a recurrent, multisystem inflammation and immune-related disease. Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and polymorphisms of the PTPN22 gene have been shown to be associated with various immune-related diseases. The present study was performed to assess the association between PTPN22 polymorphisms and Behcet's disease in two Chinese Han populations. A total of 516 patients with ocular Behcet's disease and 690 healthy controls from two Chinese Han populations were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for three single nucleotide polymorphisms (SNPs). Hardy-Weinberg equilibrium was tested using the χ(2) test. Genotype frequencies were estimated through direct counting. Allele and genotype frequencies were compared between patients and controls using logistic regression analysis. The results revealed that there was no association between the tested three PTPN22 SNPs (rs2488457, rs1310182 and rs3789604) and ocular Behcet's disease (p>0.05). Categorization analysis according to the clinical features did not show any association of these three polymorphisms with these parameters (p>0.05). The investigated PTPN22 gene polymorphisms (rs2488457, rs1310182 and rs3789604) were not associated with ocular Behcet's disease in two Chinese Han populations, and showed that it may be different from other classical autoimmune diseases. More studies are needed to confirm these findings for Behcet's disease in other ethnic backgrounds.


Using Molecular Strain and Aromaticity To Create Ultraweak C-H Bonds and Stabilized Carbon-Centered Radicals.
An approach based on relief of molecular strain in the parent hydrocarbon, extended conjugation in the radical, and the driving force toward aromaticity is used to design molecules with ultraweak C-H bonds. The molecular strain is generated by two fused rings containing (5,5)-, (5,6)-, or (6,6)-membered ring structures. Homodesmotic reactions are used to calculate the molecular strain enthalpy (MSE) of the parent hydrocarbons and the corresponding radicals, and to analyze how it changes through these reactions. B3LYP calculations are used to obtain the bond dissociation enthalpies (BDEs) for breaking one or more C-H bonds as well as the C-O bond formed after oxygen addition to the radical. Loss of a second H-atom can lead to very low R-H BDE values, especially when the ultimate product is aromatic. Molecular structures based on these ideas may be of interest as novel antioxidants based on carbon-centered radicals.


The anesthetic considerations of tracheobronchial foreign bodies in children: a literature review of 12,979 cases.
Asphyxiation by an inhaled foreign body is a leading cause of accidental death among children younger than 4 years. We analyzed the recent epidemiology of foreign body aspiration and reviewed the current trends in diagnosis and management. In this article, we discuss anesthetic management of bronchoscopy to remove objects. The reviewed articles total 12,979 pediatric bronchoscopies. Most aspirated foreign bodies are organic materials (81%, confidence interval [CI] = 77%-86%), nuts and seeds being the most common. The majority of foreign bodies (88%, CI = 85%-91%) lodge in the bronchial tree, with the remainder catching in the larynx or trachea. The incidence of right-sided foreign bodies (52%, CI = 48%-55%) is higher than that of left-sided foreign bodies (33%, CI = 30%-37%). A small number of objects fragment and lodge in different parts of the airways. Only 11% (CI = 8%-16%) of the foreign bodies were radio-opaque on radiograph, with chest radiographs being normal in 17% of children (CI = 13%-22%). Although rigid bronchoscopy is the traditional diagnostic "gold standard," the use of computerized tomography, virtual bronchoscopy, and flexible bronchoscopy is increasing. Reported mortality during bronchoscopy is 0.42%. Although asphyxia at presentation or initial emergency bronchoscopy causes some deaths, hypoxic cardiac arrest during retrieval of the object, bronchial rupture, and unspecified intraoperative complications in previously stable patients constitute the majority of in-hospital fatalities. Major complications include severe laryngeal edema or bronchospasm requiring tracheotomy or reintubation, pneumothorax, pneumomediastinum, cardiac arrest, tracheal or bronchial laceration, and hypoxic brain damage (0.96%). Aspiration of gastric contents is not reported. Preoperative assessment should determine where the aspirated foreign body has lodged, what was aspirated, and when the aspiration occurred ("what, where, when"). The choices of inhaled or IV induction, spontaneous or controlled ventilation, and inhaled or IV maintenance may be individualized to the circumstances. Although several anesthetic techniques are effective for managing children with foreign body aspiration, there is no consensus from the literature as to which technique is optimal. An induction that maintains spontaneous ventilation is commonly practiced to minimize the risk of converting a partial proximal obstruction to a complete obstruction. Controlled ventilation combined with IV drugs and paralysis allows for suitable rigid bronchoscopy conditions and a consistent level of anesthesia. Close communication between the anesthesiologist, bronchoscopist, and assistants is essential.


Equivalent pain relief with and without resection of the posterior tibial tendon in adult flatfoot reconstruction.
Transfer of the flexor digitorum longus (FDL) is indicated to compensate for the loss of posterior tibial tendon (PTT) function in the treatment of adult acquired flatfoot deformity (AAFD). The aim of this study was to determine the effect of PTT resection on pain relief following surgical treatment of stage II AAFD. A retrospective review of patients who underwent surgical treatment for stage II AAFD was performed. Patients were divided into two groups based on whether the degenerated PTT was resected or left in situ. A visual analog scale (VAS) score for pain was recorded for each patient preoperatively. Concomitant surgical procedures and the incidence of postoperative pain were also reported for each group. Deformity correction was assessed with standard weight-bearing radiographs. Thirty-four patients with a mean follow-up of 14 months were included in the study. There was no difference in preoperative VAS pain scores, and patients in both groups demonstrated excellent pain relief postoperatively. Five patients in the PTT resection group and one patient in the PTT in situ group reported lateral-sided foot pain postoperatively. Resection of the PTT did not significantly affect postoperative pain relief. Future prospective studies are needed to determine whether resection of the degenerated PTT is necessary at the time of surgery for stage II AAFD.


A multicenter, randomized controlled comparison of three renutrition strategies for the management of moderate acute malnutrition among children aged from 6 to 24 months (the MALINEA project).
The aim of this open-label, randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic, and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment. To be included, children aged between 6 months and 2 years are preselected based on mid-upper-arm circumference (MUAC) and are included based on a weight-for-height Z-score (WHZ) between - 3 and - 2 standard deviations (SD). As per current protocols, children receive renutrition treatment for 12 weeks and are assessed weekly to determine improvement. The primary endpoint is recovery, defined by a WHZ ≥ - 1.5 SD after 12 weeks of treatment. Data collected include clinical and socioeconomic characteristics, side effects, compliance and tolerance to interventions. Metagenomic analysis of gut microbiota is conducted at inclusion, 3 months, and 6 months. The cognitive development of children is evaluated in Senegal using only the Developmental Milestones Checklist II (DMC II) questionnaire at inclusion and at 3, 6, and 9 months. The data will be correlated with renutrition efficacy and metagenomic data. This study will provide new insights for the treatment of MAM, as well as original data on the modulation of gut microbiota during the renutrition process to support (or not) the microbiota hypothesis of malnutrition. ClinicalTrials.gov, ID: NCT03474276 Last update 28 May 2018.


Microcirculation in obesity: an unexplored domain.
Obesity is traditionally linked to diabetes and cardiovascular diseases. Very recent experimental, clinical and epidemiological, sometimes provocative, data challenge this automaticity by showing that not the amount but the distribution of fat is the important determinant. Moderate abdominal fat accumulation may thus be more harmful than even consequent overweight. In view of the worldwide burden of obesity, factors leading to it in children and young adults must urgently be identified. Since obesity is a very complex cardiometabolic situation, this will require to focus investigations on uncomplicated obese subjects and adequate animal models. The recent discovery of intergenerational transmissions of obesity risk factors and also the key role played by gestational and perinatal events (epigenetic factors) give rise to completely new concepts and research avenues. Considering the potential close relationship between microcirculation and tissue metabolism, demonstrations of structural and/or functional abnormalities in microvascular physiology very early in life of subjects at risk for obesity might provide a solid basis for further investigations of such links. Microcirculation(arterioles, capillaries and venules) is conceivably a key compartment determining over one or several decades the translation of genetic and epigenetic factors into fat accumulation. Available animal models should serve to answer this cardinal question.


Inferring the potential risks of H7N9 infection by spatiotemporally characterizing bird migration and poultry distribution in eastern China.
In view of the rapid geographic spread and the increasing number of confirmed cases of novel influenza A(H7N9) virus infections in eastern China, we developed a diffusion model to spatiotemporally characterize the impacts of bird migration and poultry distribution on the geographic spread of H7N9 infection. Three types of infection risks were estimated for 12 weeks, from February 4 to April 28, 2013, including (i) the risk caused by bird migration, (ii) the risk caused by poultry distribution, and (iii) the integrated risk caused by both bird migration and poultry distribution. To achieve this, we first developed a method for estimating the likelihood of bird migration based on available environmental and meteorological data. Then, we adopted a computational mobility model to estimate poultry distribution based on annual poultry production and consumption of each province/municipality. Finally, the spatiotemporal risk maps were created based on the integrated impacts of both bird migration and poultry distribution. In the study of risk estimation caused by bird migration, the likelihood matrix was estimated based on the 7-day temperature, from February 4 to April 28, 2013. It was found the estimated migrant birds mainly appear in the southeastern provinces of Zhejiang, Shanghai and Jiangsu during Weeks 1 to 4, and Week 6, followed by appearing in central eastern provinces of Shandong, Hebei, Beijing, and Tianjin during Weeks 7 to 9, and finally in northeastern provinces of Liaoning, Jilin, and Heilongjiang during Weeks 10 to 12.In the study of risk caused by poultry distribution, poultry distribution matrix was created to show the probability of poultry distribution. In spite of the fact that the majority of the initial infections were reported in Shanghai and Jiangsu, the relative risk of H7N9 infection estimated based on the poultry distribution model predicted that Jiangsu may have a slightly higher likelihood of H7N9 infection than those in Zhejiang and Shanghai, if we only take the probability of poultry distribution into consideration.In the study of integrated risk caused by both bird migration and poultry distribution, the higher risk in southeastern provinces occurred during the first 8 weeks, and that in central eastern provinces appeared during Weeks 8 to 12, and that in northeastern provinces since Week 12. Therefore, it is necessary to regulate the poultry markets as long as the poultry-to-poultry transmission is not so well understood. With reference to the reported infection cases, the demonstrated risk mapping results will provide guidance in active surveillance and control of human H7N9 infections by taking intensive intervention in poultry markets.


Flash, the emperor and policies without evidence: counter-terrorism measures destined for failure and societally divisive.
Governments around the world are uniting in trying to defeat terrorist movements. In this context, recent counter terrorism laws in the UK place public duties on all citizens to help prevent terrorism. Yet, the science of predicting rare events such as terrorist offending yields consistently poor results. There are ethical, clinical and scientific dilemmas facing the professions if we are to investigate social, religious and political belief systems in routine assessment in order to inform judgements about terrorist offending risk. A balanced and evidence-based approach is necessary.


Tissue cohesion and the mechanics of cell rearrangement.
Morphogenetic processes often involve the rapid rearrangement of cells held together by mutual adhesion. The dynamic nature of this adhesion endows tissues with liquid-like properties, such that large-scale shape changes appear as tissue flows. Generally, the resistance to flow (tissue viscosity) is expected to depend on the cohesion of a tissue (how strongly its cells adhere to each other), but the exact relationship between these parameters is not known. Here, we analyse the link between cohesion and viscosity to uncover basic mechanical principles of cell rearrangement. We show that for vertebrate and invertebrate tissues, viscosity varies in proportion to cohesion over a 200-fold range of values. We demonstrate that this proportionality is predicted by a cell-based model of tissue viscosity. To do so, we analyse cell adhesion in Xenopus embryonic tissues and determine a number of parameters, including tissue surface tension (as a measure of cohesion), cell contact fluctuation and cortical tension. In the tissues studied, the ratio of surface tension to viscosity, which has the dimension of a velocity, is 1.8 µm/min. This characteristic velocity reflects the rate of cell-cell boundary contraction during rearrangement, and sets a limit to rearrangement rates. Moreover, we propose that, in these tissues, cell movement is maximally efficient. Our approach to cell rearrangement mechanics links adhesion to the resistance of a tissue to plastic deformation, identifies the characteristic velocity of the process, and provides a basis for the comparison of tissues with mechanical properties that may vary by orders of magnitude.


DIGRE: Drug-Induced Genomic Residual Effect Model for Successful Prediction of Multidrug Effects.
Multidrug regimens are a promising strategy for improving therapeutic efficacy and reducing side effects, especially for complex disorders such as cancer. However, the use of multidrug therapies is very challenging, due to a lack of understanding of the mechanisms of drug interactions. We herein present a novel computational approach-Drug-Induced Genomic Residual Effect (DIGRE) Computational Model-to predict drug combination effects by explicitly modeling drug response curves and gene expression changes after drug treatments. The prediction performance of DIGRE was evaluated using two datasets: (i) OCI-LY3 B-lymphoma cells treated with 14 different drugs and (ii) MCF breast cancer cells treated with combinations of gefitinib and docetaxel at different doses. In both datasets, the predicted drug combination effects significantly correlated with the experimental results. The results indicated the model was useful in predicting drug combination effects, which may greatly facilitate the discovery of new, effective multidrug therapies.


Insights from modeling studies on how climate change affects invasive alien species geography.
Climate change and biological invasions are threatening biodiversity and ecosystem services worldwide. It has now been widely acknowledged that climate change will affect biological invasions. A large number of studies have investigated predicted shifts and other changes in the geographic ranges of invasive alien species related to climate change using modeling approaches. Yet these studies have provided contradictory evidence, and no consensus has been reached. We conducted a systematic review of 423 modeling case studies included in 71 publications that have examined the predicted effects of climate change on those species. We differentiate the approaches used in these studies and synthesize their main results. Our results reaffirm the major role of climate change as a driver of invasive alien species distribution in the future. We found biases in the literature both regarding the taxa, toward plants and invertebrates, and the areas of the planet investigated. Despite these biases, we found for the plants and vertebrates studied that climate change will more frequently contribute to a decrease in species range size than an increase in the overall area occupied. This is largely due to oceans preventing terrestrial invaders from spreading poleward. In contrast, we found that the ranges of invertebrates and pathogens studied are more likely to increase following climate change. An important caveat to these findings is that researchers have rarely considered the effects of climate change on transport, introduction success, or the resulting impacts. We recommend closing these research gaps, and propose additional avenues for future investigations, as well as opportunities and challenges for managing invasions under climate change.


Semantic processing during morphological priming: an ERP study.
Previous research has yielded conflicting results regarding the onset of semantic processing during morphological priming. The present study was designed to further explore the time-course of morphological processing using event-related potentials (ERPs). We conducted a primed lexical decision study comparing a morphological (LAVAGE - laver [washing - wash]), a semantic (LINGE - laver [laundry - wash]), an orthographic (LAVANDE - laver [lavender - wash]), and an unrelated control condition (HOSPICE - laver [nursing home - wash]), using the same targets across the four priming conditions. The behavioral data showed significant effects of morphological and semantic priming, with the magnitude of morphological priming being significantly larger than the magnitude of semantic priming. The ERP data revealed significant morphological but no semantic priming at 100-250 ms. Furthermore, a reduction of the N400 amplitude in the morphological condition compared to the semantic and orthographic condition demonstrates that the morphological priming effect was not entirely due to the semantic or orthographic overlap between the prime and the target. The present data reflect an early process of semantically blind morphological decomposition, and a later process of morpho-semantic decomposition, which we discuss in the context of recent morphological processing theories.


Effects of fasting on insulin binding, glucose transport, and glucose oxidation in isolated rat adipocytes: relationships between insulin receptors and insulin action.
Insulin binding, glucose transport, and glucose oxidation were studied in isolated adipocytes obtained from fasting rats. Fasting led to an increase in the overall binding affinity for insulin, while the number of receptor sites per cell remained constant. Glucose oxidation was markedly attenuated during fasting. Basal rates of oxidation decreased by about 50%, while insulin-stimulated rates decreased 6 to 10-fold. Glucose transport was assessed by measuring initial uptake rate of 2-deoxy-glucose. Fasting led to a 40-50% decrease in the apparent maximal transport capacity (Vmax) of 2-deoxy-glucose uptake with no change in apparent Km. A progressive decrease in basal and insulin-stimulated rates of 2-deoxy-glucose uptake was seen from 24-72 h of starvation and a significant correlation (r=0.85, P less than 0.001) existed between basal and maximal insulin-stimulated uptake rates in individual animals. When 2-deoxy-glucose uptake was plotted as a function of insulin bound, due to the decrease in maximal uptake capacity, cells from fasting animals took up less hexose for any amount of insulin bound. When the insulin bound was plotted as a function of the percent insulin effect on uptake, control cells and cells from 24-h-fasted rats gave comparable results, while cells from 48- and 72-h-fasted animals still took up less hexose for any amount of bound insulin. The effects of fasting on 3-O-methyl glucose uptake were comparable to the 2-deoxy-glucose data. (a) insulin binding is increased during fasting due to an increased overall binding affinity with no change in receptor number; (b) glucose oxidation is severely impaired during fasting; (c) 2-deoxy-glucose uptake decreases with fasting due to a decrease in maximal transport capacity (Vmax) with no change in Km; (d) the decrease in glucose oxidation is much greater than the decrease in glucose transport, indicating impaired intracellular oxidative metabolism; and (e) coupling between insulin receptors and the glucose transport system is normal after 24 h of fasting but is impaired at 48 and 72 h.


Relationship Between Fuchs Endothelial Corneal Dystrophy Severity and Glaucoma and/or Ocular Hypertension.
OBJECTIVE To investigate whether Fuchs endothelial corneal dystrophy (FECD) severity is associated with glaucoma and/or ocular hypertension (G/OHTN). METHODS A subset of eyes (n = 1610) from the FECD Genetics Multi-Center Study were examined to estimate the association between FECD severity (grades 0-6 based on guttae confluence) and G/OHTN. Logistic regression models that accounted for the correlation between eyes and adjusted for age, sex, central corneal thickness, intraocular pressure, presence of diabetes, and time of day of the initial evaluation were fit. RESULTS A total of 107 eyes (6.6%) had G/OHTN based on the study definition. The prevalence of G/OHTN in the control group was 6.0%. The prevalence was lower in index cases with an FECD grade of 1 through 3 and family members with a grade of 0 or 1 through 3 (0.0% and 2.1%, respectively) but higher in index cases and family members with a grade of 4 through 6 (11.2% and 8.5%, respectively). Adjusting for covariates, eyes with a grade of 4 through 6 were more likely to have concurrent G/OHTN than eyes with no FECD (index cases vs controls: odds ratio [OR] = 2.10, P = .04; affected vs unaffected family members: OR = 7.06, P = .07). Age (OR = 1.06 per 1-year increase, P < .001) and intraocular pressure (OR = 1.15 per 1-mm Hg increase, P < .001) were also associated with an increased prevalence of G/OHTN. Sex, diabetes, time of day of evaluation, and central corneal thickness were not associated with the prevalence of G/OHTN (P ≥ .15). CONCLUSIONS Glaucoma and/or ocular hypertension occurs more often in eyes with severe FECD compared with unaffected eyes. Therefore, it may be beneficial to monitor for the development of glaucoma in these patients.