Temporomandibular joint dislocation in Nairobi.
Despite the diverse conservative and surgical modalities for the management of temporomandibular joint (TMJ) dislocation and the controversy that surrounds them, very little has been done within the East-African setup in terms of highlighting and provoking greater interest in the epidemiology and management of TMJ dislocation. To audit the pattern of occurrence, demographics, aetiology and enumerate the treatment modalities of TMJ dislocation at the oral and maxillofacial surgery division (OMFS) of the University of Nairobi Dental Hospital. Descriptive cross-sectional study. University of Nairobi Dental Hospital (UNDH) from January 1995 to July 2005. Twenty nine patients had been diagnosed and managed for TMJ dislocation. Twenty (69%) were females and nine (31%) were males. Their ages ranged from 10-95 years with a mean of 42 years. The cases managed were primarily chronic in nature. The most common form being anterior TMJ dislocation, accounting for twenty-five (86.2%) cases. Trauma was implicated as an aetiology in only five (17%) of the cases while the remaining majority of twenty four (83%) cases were spontaneous. Amongst the causes of spontaneous TMJ dislocation, yawning was the most common accounting for fourteen cases (48.3%). Dislocations caused by trauma were found to be 12.6 times more likely to be associated with other injuries than spontaneous dislocations. Anterior TMJ dislocations were found to be 1.3 times more likely to be associated with absence of molars than posterior TMJ dislocations. Anatomical aberrations, as predisposing factors, were not a significant finding in this research. Eight (28%) of the cases were managed conservatively. Twenty one (72%) of the cases were managed surgically. The eminectomy was the most common technique with a 75% success rate. The highest incidence of TMJ dislocation occurs in the 3rd-5th decade with a female preponderance with bilateral anterior TMJ dislocation being the most common. Most of the cases were managed surgically with eminectomy being the preferred technique with the highest success rate. A study needs to be undertaken to determine reasons' why conservative modalities are least employed in the management of TMJ dislocation in our setup and what can be done about it.


Design thinking.
In the past, design has most often occurred fairly far downstream in the development process and has focused on making new products aesthetically attractive or enhancing brand perception through smart, evocative advertising. Today, as innovation's terrain expands to encompass human-centered processes and services as well as products, companies are asking designers to create ideas rather than to simply dress them up. Brown, the CEO and president of the innovation and design firm IDEO, is a leading proponent of design thinking--a method of meeting people's needs and desires in a technologically feasible and strategically viable way. In this article he offers several intriguing examples of the discipline at work. One involves a collaboration between frontline employees from health care provider Kaiser Permanente and Brown's firm to reengineer nursing-staff shift changes at four Kaiser hospitals. Close observation of actual shift changes, combined with brainstorming and rapid prototyping, produced new procedures and software that radically streamlined information exchange between shifts. The result was more time for nursing, better-informed patient care, and a happier nursing staff. Another involves the Japanese bicycle components manufacturer Shimano, which worked with IDEO to learn why 90% of American adults don't ride bikes. The interdisciplinary project team discovered that intimidating retail experiences, the complexity and cost of sophisticated bikes, and the danger of cycling on heavily trafficked roads had overshadowed people's happy memories of childhood biking. So the team created a brand concept--"Coasting"--to describe a whole new category of biking and developed new in-store retailing strategies, a public relations campaign to identify safe places to cycle, and a reference design to inspire designers at the companies that went on to manufacture Coasting bikes.


CCR5 inhibition prevents cardiac dysfunction in the SIV/macaque model of HIV.
Diastolic dysfunction is a highly prevalent cardiac abnormality in asymptomatic as well as ART-treated human immunodeficiency virus (HIV) patients. Although the mechanisms underlying depressed cardiac function remain obscure, diastolic dysfunction in SIV-infected rhesus macaques is highly correlated with myocardial viral load. As cardiomyocytes are not productively infected, damage may be an indirect process attributable to a combination of pro-inflammatory mediators and viral proteins. Given the diverse roles of CCR5 in mediating recruitment of leukocytes to inflammatory sites and serving as a receptor for HIV entry into cells, we investigated the role of CCR5 in the SIV/macaque model of diastolic dysfunction. We found that in SIV-infected macaques, CCR5 inhibition dramatically impacted myocardial viral load measured by qRT-PCR and prevented diastolic dysfunction measured by echocardiography. Complementary in vitro experiments using fluorescence microscopy showed that CCR5 ligands impaired contractile function of isolated cardiomyocytes, thus identifying CCR5 signaling as a novel mediator of impaired cardiac mechanical function. Together, these findings incriminate SIV/HIV gp120-CCR5 as well as chemokine-CCR5 interactions in HIV-associated cardiac dysfunction. These findings also have important implications for the treatment of HIV-infected individuals: in addition to antiviral properties and reduced chemokine-mediated recruitment and activation of inflammatory cells, CCR5 inhibition may provide a cardioprotective benefit by preventing cardiomyocyte CCR5 signaling.


Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores.
Osteoarthritis trials usually report average changes in visual analogue scale (VAS) pain, and examine the difference between treatment and placebo. We investigated whether dichotomous responder analysis provides a more informative interpretation of drug efficacy. Merck supplied the number of patients who, by 6 weeks, had achieved pain relief compared with a baseline of 0% or more, 10% or more, 20% or more, and so on at equal intervals up to 90% or more. These different levels of pain relief were used to distinguish different definitions of responders, for example at least 50% pain relief from baseline. Numbers and percentages of patients achieving each level were identified. Information was sought from a dose-response trial over 6 weeks in osteoarthritis using placebo and using etoricoxib at 5, 10, 30 and 60 mg daily. With placebo, the proportions of patients achieving at least 20%, 50% and 70% pain relief over baseline at 6 weeks were 30%, 11% and 2%. With 60 mg etoricoxib the equivalent percentages were 74%, 49% and 29%. The numbers needed to treat for 30 mg and 60 mg etoricoxib to produce at least 50% pain relief at 6 weeks compared with placebo were 4.2 (95% confidence interval 3.8 to 8.6) and 2.6 (2.0 to 3.9), respectively. Levels of pain relief of 50% and above discriminated best between different doses of etoricoxib. Responder analysis seemed to be more sensitive than examination of average changes in VAS pain scores. Validation would require calculations to be performed on a set of trials using individual patient data not available in publications.


The association between hantavirus infection and selenium deficiency in mainland China.
Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.


Gene profiling of early and advanced liver disease in chronic hepatitis C patients.
Strong impact of hepatitis C virus (HCV) on normal regulation of cellular processes has been reported that could have significant implications for HCV pathogenesis. We aimed to determine the altered cellular processes during HCV infection with particular reference to advanced disease stages. Liver biopsy specimens of chronic hepatitis C patients classified on histological basis as early (fibrosis stage 1-2) or advanced (fibrosis stage 3-4) HCV disease were studied using microarray technology (Affymetrix GeneChip™ System). For comparison, liver specimens from patients with non-viral hepatitis (NV-hepatitis) were also analyzed by microarray. Expression data generated were analyzed using software Genespring GX and Ingenuity Pathway analysis to find the association with biological functions. We further validated the microarray results using quantitative reverse transcriptase-polymerase chain reaction. Data analysis through Genespring software revealed that in advanced HCV (A-HCV) a total of 792 genes are differentially expressed when compared to early HCV (E-HCV) and 417 genes are differentially expressed when compared to NV-hepatitis. Most of these genes are involved in cancer, cellular growth and proliferation, and tissue morphology. Real time (RT) PCR analysis confirmed the differential expression of six of these genes. The results of this study reflect the changes taking place during the transition from early to advanced liver fibrosis, when the liver function becomes impaired and extracellular matrix deposition increases. In addition, it showed altered expression of genes with functions in cancer development, cell growth, proliferation, and cell death that might indicate high risk of cell transformation and hepatocellular carcinoma (HCC) in A-HCV disease patients.


Outcome Trajectories and Prognostic Factors for Suicide and Self-Harm Behaviors in Patients With Borderline Personality Disorder Following One Year of Outpatient Psychotherapy.
This study examined suicide and self-harm trajectories in 180 individuals with BPD receiving dialectical behavior therapy or general psychiatric management in a randomized controlled trial. Suicide and self-harm behaviors were assessed at baseline, every four months throughout treatment, and every 6 months over 2 years of follow-up. Latent class growth mixture modeling identified suicide and self-harm trajectories. Multinomial logistic regression analyses examined baseline patient characteristics. Three latent subgroups were identified. The largest responded rapidly to treatment and sustained a favorable response post-discharge. The second progressed slowly during treatment but achieved and maintained a favorable response. A third subgroup showed a rapid favorable response during treatment, however symptoms returned to near baseline levels post-discharge. This third subgroup had higher baseline depression, emergency department visits, and unemployment. BPD patients with high baseline health care utilization, depression, and unemployment may benefit from modifications to treatment specifically targeting these issues.


DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition.
Here, we explore whether silencing via promoter DNA methylation plays a role in neural versus neural crest cell lineage decisions. We show that DNA methyltransferase3A (DNMT3A) promotes neural crest specification by directly mediating repression of neural genes like Sox2 and Sox3. DNMT3A is expressed in the neural plate border, and its knockdown causes ectopic Sox2 and Sox3 expression at the expense of neural crest markers. In vivo chromatin immunoprecipitation of neural folds demonstrates that DNMT3A specifically associates with CpG islands in the Sox2 and Sox3 promoter regions, resulting in their repression by methylation. Thus, DNMT3A functions as a molecular switch, repressing neural to favor neural crest cell fate.


Gratings that induce perceptual distortions mask superimposed targets.
Masking is known to depend upon the relationship between the spatial-frequency content of target and mask. This relationship has been held constant in three experiments in order to investigate the separate contribution of the spatial parameters of the mask, in this case a grating with square-wave luminance profile. Thresholds for the detection of a probe target were highest when the background grating upon which the probe was superimposed had a spatial frequency of about 4 cycles deg-1 (experiment 1) and a duty cycle of 50% (experiment 3). In experiment 2, the thresholds were strongly affected by the size of the background grating even though the size of the target was small in proportion to the grating and remained constant. The increase in threshold was linearly related to the area of visual cortex to which the grating projected. The spatial parameters of gratings that maximise masking are therefore the same as those that have been shown to be optimal for the induction of perceptual distortions, suggesting a possible physiological mechanism for both the masking and the distortions.


Evidence of systematic expressed sequence tag IMAGE clone cross-hybridization on cDNA microarrays.
We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5'-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive 5'-end dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5' poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5' poly(dT) tracts.


Rationing critical care beds: a systematic review.
Rationing critical care beds occurs daily in the hospital setting. The objective of this systematic review was to examine the impact of rationing intensive care unit beds on the process and outcomes of care. We searched MEDLINE (1966-2003), CINAHL (1982-2003), Ovid Healthstar (1975-2003), EMBASE (1980-2003), Scisearch (1980-2003), the Cochrane Library, PUBMED related articles, personal files, abstract proceedings, and reference lists. We included studies of seriously ill patients considered for admission to an intensive care unit bed during periods of reduced availability. We had no restriction on study design. Studies were excluded if rationing was performed using a scoring system or protocol and if cost-effectiveness was the only outcome. In duplicate and independently, we performed data abstraction and quality assessment. We included ten observational studies. Hospital mortality rate was increased in patients refused intensive care unit admission vs. those admitted (odds ratio, 3.04; 95% confidence interval, 1.49-6.17). Factors associated with both intensive care unit bed refusal and increased mortality rate were increased age, severity of illness, and medical diagnosis. When intensive care unit beds were reduced, admitted patients were sicker, were less often admitted primarily for monitoring, and had a shorter intensive care unit length of stay, without other observed adverse effects. These studies suggest that patients who are perceived not to benefit from critical care are more often refused intensive care unit admission; refusal is associated with an increased risk of hospital death. During times of decreased critical bed availability, several factors, including age, illness severity, and medical diagnosis, are used to triage patients, although their relative importance is uncertain. Critical care bed rationing requires further investigation.


Comparing depth from motion with depth from binocular disparity.
The accuracy of depth judgments that are based on binocular disparity or structure from motion (motion parallax and object rotation) was studied in 3 experiments. In Experiment 1, depth judgments were recorded for computer simulations of cones specified by binocular disparity, motion parallax, or stereokinesis. In Experiment 2, judgments were recorded for real cones in a structured environment, with depth information from binocular disparity, motion parallax, or object rotation about the y-axis. In both of these experiments, judgments from binocular disparity information were quite accurate, but judgments on the basis of geometrically equivalent or more robust motion information reflected poor recovery of quantitative depth information. A 3rd experiment demonstrated stereoscopic depth constancy for distances of 1 to 3 m using real objects in a well-illuminated, structured viewing environment in which monocular depth cues (e.g., shading) were minimized.


Mono- and bimetallic zwitterionic chromium(0) and tungsten(0) allenyls.
A series of stable chiral (racemic), formally neutral, zwitterionic mono- and bimetallic M(CO)5[C(OEt)═C═CR(NHC)] (M = Cr, W) σ-allenyls are ready available by the addition of N-heterocyclic carbenes (NHCs) to Cr(0) and W(0) alkynyl Fischer carbene complexes. Different classes of NHCs, (e.g., 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene, and their six- and seven-membered analogues and 1,3-bis(dimethyl)imidazol-2-ylidene) were employed as nucleophiles in these C-C bond-forming reactions yielding the novel complexes in essentially quantitative yields. A systematic experimental and computational study of the electronic properties of the Cr- and W-allenyls shows that their UV-vis spectra are directly influenced by the structure of the heterocyclic moiety derived from the NHC (ring size, substituents on the N atoms) and by the nature of the metal fragment (Cr/W). The electron-releasing nature of these complexes allows them to participate in electron-transfer reactions in the ground state, leading to a type of charged α,β-unsaturated Fischer carbenes that incorporate an NHC fragment in their structure.


What's fair? How children assign reward to members of teams with differing causal structures.
How do children reward individual members of a team that has just won or lost a game? We know that from pre-school age, children consider agents' performance when allocating reward. Here we assess whether children can go further and appreciate performance in context: The same pattern of performance can contribute to a team outcome in different ways, depending on the underlying rule framework. Two experiments, with three age groups (4/5-year-olds, 6/7-year-olds, and adults), varied performance of team members, with the same performance patterns considered under three different game rules for winning or losing. These three rules created distinct underlying causal structures (additive, conjunctive, disjunctive), for how individual performance affected the overall team outcome. Even the youngest children differentiated between different game rules in their reward allocations. Rather than only rewarding individual performance, or whether the team won/lost, children were sensitive to the team structure and how players' performance contributed to the win/loss under each of the three game rules. Not only do young children consider it fair to allocate resources based on merit, but they are also sensitive to the causal structure of the situation which dictates how individual contributions combine to determine the team outcome.


Virtual Animals as Diegetic Attention Guidance Mechanisms in 360-Degree Experiences.
360-degree experiences such as cinematic virtual reality and 360-degree videos are becoming increasingly popular. In most examples, viewers can freely explore the content by changing their orientation. However, in some cases, this increased freedom may lead to viewers missing important events within such experiences. Thus, a recent research thrust has focused on studying mechanisms for guiding viewers' attention while maintaining their sense of presence and fostering a positive user experience. One approach is the utilization of diegetic mechanisms, characterized by an internal consistency with respect to the narrative and the environment, for attention guidance. While such mechanisms are highly attractive, their uses and potential implementations are still not well understood. Additionally, acknowledging the user in 360-degree experiences has been linked to a higher sense of presence and connection. However, less is known when acknowledging behaviors are carried out by attention guiding mechanisms. To close these gaps, we conducted a within-subjects user study with five conditions of no guide and virtual arrows, birds, dogs, and dogs that acknowledge the user and the environment. Through our mixed-methods analysis, we found that the diegetic virtual animals resulted in a more positive user experience, all of which were at least as effective as the non-diegetic arrow in guiding users towards target events. The acknowledging dog received the most positive responses from our participants in terms of preference and user experience and significantly improved their sense of presence compared to the non-diegetic arrow. Lastly, three themes emerged from a qualitative analysis of our participants' feedback, indicating the importance of the guide's blending in, its acknowledging behavior, and participants' positive associations as the main factors for our participants' preferences.


Yoga for veterans with chronic low back pain: Design and methods of a randomized clinical trial.
Chronic low back pain (CLBP) afflicts millions of people worldwide, with particularly high prevalence in military veterans. Many treatment options exist for CLBP, but most have limited effectiveness and some have significant side effects. In general populations with CLBP, yoga has been shown to improve health outcomes with few side effects. However, yoga has not been adequately studied in military veteran populations. In the current paper we will describe the design and methods of a randomized clinical trial aimed at examining whether yoga can effectively reduce disability and pain in US military veterans with CLBP. A total of 144 US military veterans with CLBP will be randomized to either yoga or a delayed treatment comparison group. The yoga intervention will consist of 2× weekly yoga classes for 12weeks, complemented by regular home practice guided by a manual. The delayed treatment group will receive the same intervention after six months. The primary outcome is the change in back pain-related disability measured with the Roland-Morris Disability Questionnaire at baseline and 12-weeks. Secondary outcomes include pain intensity, pain interference, depression, anxiety, fatigue/energy, quality of life, self-efficacy, sleep quality, and medication usage. Additional process and/or mediational factors will be measured to examine dose response and effect mechanisms. Assessments will be conducted at baseline, 6-weeks, 12-weeks, and 6-months. All randomized participants will be included in intention-to-treat analyses. Study results will provide much needed evidence on the feasibility and effectiveness of yoga as a therapeutic modality for the treatment of CLBP in US military veterans.


Infant sustained attention but not joint attention to objects at 9 months predicts vocabulary at 12 and 15 months.
Vocabulary differences early in development are highly predictive of later language learning as well as achievement in school. Early word learning emerges in the context of tightly coupled social interactions between the early learner and a mature partner. In the present study, we develop and apply a novel paradigm-dual head-mounted eye tracking-to record momentary gaze data from both parents and infants during free-flowing toy-play contexts. With fine-grained sequential patterns extracted from continuous gaze streams, we objectively measure both joint attention and sustained attention as parents and 9-month-old infants played with objects and as parents named objects during play. We show that both joint attention and infant sustained attention predicted vocabulary sizes at 12 and 15 months, but infant sustained attention in the context of joint attention, not joint attention itself, is the stronger unique predictor of later vocabulary size. Joint attention may predict word learning because joint attention supports infant attention to the named object.


Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial.
Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. Intracoronary infusion of 150 × 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. clinicaltrials.gov Identifier: NCT00684060.


Type and distribution of indomethacin-induced lesions in the gastrointestinal tract of rat.
The therapy with non-steroidal anti-inflammatory drugs (e.g. indomethacin) is often accompanied with adverse effects in gastrointestinal tract. Aim of this experimental study was to define the time range of the creation of indomethacin-induced gastrointestinal lesions in rat (for prospective study of potential probiotic therapy). The paper follows our previous experiments where the different gastrointestinal lesions were described in the pig (Kvetina et al. 2008) Indomethacin (25mg/kg) was administered orally by a single application to rat (Wistar Han II, 200-250g). Six, 24, 48 and 72 hours after the indomethacin administration all parts of the gastrointestinal tract of six rats in each time interval were macroscopically and histologically examined. The gradual development of lesions was observed 6 hours in stomach and 24-72 hours in the intestine after the indomethacin administration. Not only the gradual development of pathophysiological alterations was observed but also the reparative phase (in stomach). 24 hours seem to be advisable time suitable for the evaluation of the probiotics effect as a potential therapy) on the indomethacin-induced gastrointestinal lesions in rats. Sensitivity of the gastrointestinal tract to the pathological lesions development seems to be higher in rats in comparison to findings described in our previous experiments in pig (Kvetina et al. 2008). This adverts to interspecies differences in the manifestation and in the dynamics of the development of gastrointestinal lesions.


Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: a retrospective study.
The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1-2) in nine patients. Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.


DNA organization in the mature sperm of several orthoptera by the method of polarized fluorescence microscopy.
Mature sperm of Acheta domesticus, Acheta assimilis, Nemobius fasciatus, Nemobius confusus, Melanoplus femur-rubrum, Romalea microptera, Scudderia curvicauda, and Ceuthophilus nigricans were examined for DNA configuration by means of polarized fluorescence microscopy. In all cases, the results suggest that the DNA lies in unsupercoiled array, predominantly parallel to the elongate sperm head axes. Detailed calculations of the factors influencing the degree of polarization of the fluorescent emission from supercoiled DNA are contained in an appendix.


Pituitary abscess: a case report.
Pituitary abscess is rare disease and the correct diagnosis is difficult because there are non-specific symptoms and it is often radiologically indistinguishable from other pituitary lesions. We present one case of pituitary abscess that constitute 0.15% of all pituitary adenomas operated in our department in the 20 years. A 49-year-old woman presented with a history of 10 months bifrontal headache. The MRI showed cystic intra and suprasellar mass with ring enhancement after contrast injection. During transsphenoidal surgery, copious yellowish pus was found. Antibiotic therapy was performed. Histological study of the cyst wall confirmed the diagnosis of pituitary abscess. Pituitary abscess should be considered in the differential diagnosis of all other cyst mass in patients with diabetes insipidus.


How do dentists and their teams incorporate evidence about preventive care? An empirical study.
To identify how dentists and their teams adopt evidence-based preventive care. A qualitative study using grounded theory methodology was conducted. We interviewed 23 participants working in eight dental practices about their experience and work processes, while adopting evidence-based preventive care. During the study, Charmaz's grounded theory methodology was employed to examine the social process of adopting preventive dental care in dental practices. Charmaz's iteration of the constant comparative method was used during the data analysis. This involved coding of interview transcripts, detailed memo-writing and drawing diagrams. The transcripts were analyzed as soon as possible after each round of interviews in each dental practice. Coding was conducted primarily by AS, supported by team meetings and discussions when researchers compared their interpretations. Participants engaged in a slow process of adapting evidence-based protocols and guidelines to the existing logistics of the practices. This process was influenced by practical, philosophical, and historical aspects of dental care, and a range of barriers and facilitators. In particular, dentists spoke spontaneously about two deeply held 'rules' underpinning continued restorative treatment, which acted as barriers to provide preventive care: (i) dentists believed that some patients were too 'unreliable' to benefit from prevention; and (ii) dentists believed that patients thought that only tangible restorative treatment offered 'value for money'. During the adaptation process, some dentists and teams transitioned from their initial state - selling restorative care - through an intermediary stage - learning by doing and educating patients about the importance of preventive care - and finally to a stage where they were offering patients more than just restorative care. Resources were needed for the adaptation process to occur, including: the ability to maintain the financial viability of the practice, appropriate technology, time, and supportive dental team relationships. The findings from this study show that with considerable effort, motivation and coordination, it is possible for dental practices to work against the dental 'mainstream' and implement prevention as their clinical norm. This study has shown that dental practice is not purely scientific, but it includes cultural, social, and economic resources that interfere with the provision of preventive care.


BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.
Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9 and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results establish BLISS as a versatile, sensitive and efficient method for genome-wide DSB mapping in many applications.


Microscopic TV shearography for characterization of microsystems.
We demonstrate a microscopic TV shearographic configuration for characterization of microsystems by measuring the slope under relatively large out-of-plane deformation. In the optical arrangement, a long working distance zoom imaging system is combined with a conventional Michelson shear interferometer. The experimental results on a microelectromechanical system pressure sensor subjected to external pressure load are presented.


Creating a public space and dialogue on sexuality and rights: a case study from Bangladesh.
This article describes and analyses a research based engagement by a university school of public health in Bangladesh aimed at raising public debate on sexuality and rights and making issues such as discrimination more visible to policy makers and other key stakeholders in a challenging context. The impetus for this work came from participation in an international research programme with a particular interest in bridging international and local understandings of sexual and reproductive rights. The research team worked to create a platform to broaden discussions on sexuality and rights by building on a number of research activities on rural and urban men's and women's sexual health concerns, and on changing concepts of sexuality and understandings of sexual rights among specific population groups in Dhaka city, including sexual minorities. Linked to this on-going process of improving the evidence base, there has been a series of learning and capacity building activities over the last four years consisting of training workshops, meetings, conferences and dialogues. These brought together different configurations of stakeholders - members of sexual minorities, academics, service providers, advocacy organisations, media and policy makers. This process contributed to developing more effective advocacy strategies through challenging representations of sexuality and rights in the public domain. Gradually, these efforts brought visibility to hidden or stigmatised sexuality and rights issues through interim outcomes that have created important steps towards changing attitudes and policies. These included creating safe spaces for sexual minorities to meet and strategise, development of learning materials for university students and engagement with legal rights groups on sexual rights. Through this process, it was found to be possible to create a public space and dialogue on sexuality and rights in a conservative and challenging environment like Bangladesh by bringing together a diverse group of stakeholders to successfully challenge representations of sexuality in the public arena. A further challenge for BRAC University has been to assess its role as a teaching and research organisation, and find a balance between the two roles of research and activism in doing work on sexuality issues in a very sensitive political context.


Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology.
It has long been discussed whether fitness or fatness is a more important determinant of health status. If the same genetic factors that promote body fat percentage (body fat%) are related to cardiorespiratory fitness (CRF), part of the concurrent associations with health outcomes could reflect a common genetic origin. In this study we aimed to 1) examine genetic correlations between body fat% and CRF; 2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and 3) examine whether the fat mass and obesity associated (FTO) locus associates with CRF. Genetic correlations based on pedigree information were examined in a family based cohort (n = 230 from 55 families). For the genetic association analyses, we examined two Danish population-based cohorts (ntotal = 3206). The body fat% GRS was created by summing the alleles of twelve independent risk variants known to associate with body fat%. We assessed CRF as maximal oxygen uptake expressed in millilitres of oxygen uptake per kg of body mass (VO2max), per kg fat-free mass (VO2maxFFM), or per kg fat mass (VO2maxFM). All analyses were adjusted for age and sex, and when relevant, for body composition. We found a significant negative genetic correlation between VO2max and body fat% (ρG = -0.72 (SE ±0.13)). The body fat% GRS associated with decreased VO2max (β = -0.15 mL/kg/min per allele, p = 0.0034, age and sex adjusted). The body fat%-increasing FTO allele was associated with a 0.42 mL/kg/min unit decrease in VO2max per allele (p = 0.0092, age and sex adjusted). Both associations were abolished after additional adjustment for body fat%. The fat% increasing GRS and FTO risk allele were associated with decreased VO2maxFM but not with VO2maxFFM. Our findings suggest a shared genetic etiology between whole body fat% and CRF.


Novel and efficient transformation of enamides into α-acyloxy ketones via an acyl intramolecular migration process.
Hydrogen peroxide and anhydride mediated transformation of enamides to afford substituted α-acyloxy ketones is described. This transition-metal-free cascade reaction has a broad substrate scope and high efficiency. The acyl intramolecular migration procedure successfully achieved this acyloxylation process under mild conditions and increased the atom efficiency.


2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis.
To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.


Three-dimensional (3D) printing and its applications for aortic diseases.
Three-dimensional (3D) printing is a process which generates prototypes from virtual objects in computer-aided design (CAD) software. Since 3D printing enables the creation of customized objects, it is a rapidly expanding field in an age of personalized medicine. We discuss the use of 3D printing in surgical planning, training, and creation of devices for the treatment of aortic diseases. 3D printing can provide operators with a hands-on model to interact with complex anatomy, enable prototyping of devices for implantation based upon anatomy, or even provide pre-procedural simulation. Potential exists to expand upon current uses of 3D printing to create personalized implantable devices such as grafts. Future studies should aim to demonstrate the impact of 3D printing on outcomes to make this technology more accessible to patients with complex aortic diseases.


On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomes.
To determine whether children who received recommended vaccines on time during the first year of life had different neuropsychological outcomes at 7 to 10 years of age as compared with children with delayed receipt or nonreceipt of these vaccines. Publicly available data, including age at vaccination, from a previous VaccineSafety Datalink study of thimerosal exposure and 42 neuropsychological outcomes were analyzed. Vaccine receipt was defined as timely when each vaccine was received within 30 days of the recommended age. Associations between timeliness and each outcome were tested in univariate analyses. Multivariable regression models were constructed for further assessment of the impact of timeliness on neuropsychological outcomes after adjustment for potential confounders. Secondary analyses were performed on a subset of children with the highest and lowest vaccine exposures during the first 7 months of life. Timely vaccination was associated with better performance on 12 outcomes in univariate testing and remained associated with better performance for 2 outcomes in multivariable analyses. No statistically significant differences favored delayed receipt. In secondary analyses, children with the greatest vaccine exposure during the first 7 months of life performed better than children with the least vaccine exposure on 15 outcomes in univariate testing; these differences did not persist in multivariable analyses. No statistically significant differences favored the less vaccinated children. Timely vaccination during infancy has no adverse effect on neuropsychological outcomes 7 to 10 years later. These data may reassure parents who are concerned that children receive too many vaccines too soon.


A Systematic Review And Meta-Analysis of Clinical Trials of Mesenchymal Stem Cell Therapy for Cartilage Repair.
Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments. We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series. A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety. We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis.


Exosomes from Suxiao Jiuxin pill-treated cardiac mesenchymal stem cells decrease H3K27 demethylase UTX expression in mouse cardiomyocytes in vitro.
Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine for the treatment of acute coronary syndrome in China, which contains two principal components, tetramethylpyrazine (TMP) and borneol (BOR). Thus far, however, the molecular mechanisms underlying the beneficial effects of SJP on the cardiac microenvironment are unknown. Cardiac mesenchymal stem cells (C-MSCs) communicate with cardiomyocytes (CMs) through the release of microvesicles (exosomes) to restore cardiac homeostasis and elicit repair, in part through epigenetic regulatory mechanisms. In this study, we examined whether SJP treatment altered C-MSC-derived exosomes (SJP-Exos) to cause epigenetic chromatic remodeling in recipient CMs. C-MSC isolated from mouse hearts were pretreated with SJP (SJP-Exos), TMP (TMP-Exos) or BOR (BOR-Exos). Then, HL-1 cells, a mouse cardiomyocyte line, were treated with exosomes from control C-MSCs (Ctrl-Exos), SJP-Exos, TMP-Exos or BOR-Exos. Treatment with SJP-Exos significantly increased the protein levels of histone 3 lysine 27 trimethylation (H3K27me3), a key epigenetic chromatin marker for cardiac transcriptional suppression, in the HL-1 cells. To further explore the mechanisms of SJP-Exo-mediated H3K27me3 upregulation, we assessed the mRNA expression levels of key histone methylases (EZH1, EZH2 and EED) and demethylases (JMJD3 and UTX) in the exosome-treated HL-1 cells. Treatment with SJP-Exo selectively suppressed UTX expression in the recipient HL-1 cells. Furthermore, PCNA, an endogenous marker of cell replication, was significantly higher in SJP-Exo-treated HL-1 cells than in Ctrl-Exo-treated HL-1 cells. These results show that SJP-Exos increase cardiomyocyte proliferation and demonstrate that SJP can modulate C-MSC-derived exosomes to cause epigenetic chromatin remodeling in recipient cardiomyocytes; consequently, SJP-Exos might be used to promote cardiomyocyte proliferation.


Identifying optimal parameters for quantification of changes in pelvic movement symmetry as a response to diagnostic analgesia in the hindlimbs of horses.
Subjective evaluation of the response to diagnostic analgesia of hindlimb lameness is influenced by expectation bias. Quantification of pelvic movement with inertial measurement units is possible, but it is unclear which measure of movement symmetry best reflects the changes seen after diagnostic analgesia. To test our hypothesis that objective measures closely relating to those used for subjective visual lameness scoring (quantifying the difference between sacral upward or downward movement or between movement amplitudes of the left and right tubera coxae) would show the largest and most consistent response. Retrospective analysis of subjective and objective clinical lameness data. Thirteen horses with hindlimb lameness underwent visual lameness scoring and independent gait assessment with inertial measurement units. Established objective measures were calculated and changes before/after diagnostic analgesia regressed against the change in lameness grade. Slopes of regression lines were calculated and confidence intervals assessed. All objective parameters showed variation between horses and across lameness grades. The following 3 measures documented a consistent increase in symmetry for each grade of change in lameness score: difference between sacral displacement minima; upward movement difference; and range of motion difference between the tubera coxae. Several pelvic parameters are suitable for objective quantification of changes after diagnostic analgesia in hindlimb-lame horses. A change of 9-13% per lameness grade can be expected. Upward movement of the tubera coxae is the most sensitive objective measure for quantifying a response to diagnostic analgesia. However, when assessed visually, this measure requires simultaneous focusing on pelvic and limb movements. Other parameters that show a similar response might be more easily perceived, requiring only assessment of tubera coxae range of motion or downward displacement of the sacrum without simultaneous focus on limb movement.


The effects of CPAP treatment on task positive and default mode networks in obstructive sleep apnea patients: an fMRI study.
Functional magnetic resonance imaging studies enable the investigation of neural correlates underlying behavioral performance. We investigate the effect of active and sham Continuous Positive Airway Pressure (CPAP) treatment on working memory function of patients with Obstructive Sleep Apnea Syndrome (OSAS) considering Task Positive and Default Mode networks (TPN and DMN). An experiment with 4 levels of visuospatial n-back task was used to investigate the pattern of cortical activation in 17 men with moderate or severe OSAS before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment. Patients with untreated OSAS had significantly less deactivation in the temporal regions of the DMN as compared to healthy controls, but activation within TPN regions was comparatively relatively preserved. After 2 months of treatment, active and sham CPAP groups exhibited opposite trends of cerebral activation and deactivation. After treatment, the active CPAP group demonstrated an increase of cerebral activation in the TPN at all task levels and of task-related cerebral deactivation in the anterior midline and medial temporal regions of the DMN at the 3-back level, associated with a significant improvement of behavioral performance, whereas the sham CPAP group exhibited less deactivation in the temporal regions of Default Mode Network and less Task Positive Network activation associated to longer response times at the 3-back. OSAS has a significant negative impact primarily on task-related DMN deactivation, particularly in the medial temporal regions, possibly due to nocturnal hypoxemia, as well as TPN activation, particularly in the right ventral fronto-parietal network. After 2 months of active nasal CPAP treatment a positive response was noted in both TPN and DMN but without compete recovery of existing behavioral and neuronal deficits. Initiation of CPAP treatment early in the course of the disease may prevent or slow down the occurrence of irreversible impairment.


Bioinspired synthesis of pentacyclic onocerane triterpenoids.
The first chemical synthesis of pentacyclic onocerane triterpenoids has been achieved. A putative biomimetic tricyclization cascade is employed to forge a fused decalin-/oxepane ring system. The synthetic route proceeds to (+)-cupacinoxepin in seven steps and to (+)-onoceranoxide in eight steps in the longest linear sequence, when starting from geranyl chloride and (+)-sclareolide. The bioinspired epoxypolyene cyclization is supported by computational and enzymatic studies.


The Labor Analgesia Requirements in Nulliparous Women Randomized to Epidural Catheter Placement in a High or Low Intervertebral Space.
We hypothesized that an epidural catheter placed in a lower vertebral interspace will require less medication for labor analgesia. Nulliparous women requesting neuraxial labor analgesia were randomized to epidural catheter placement at the ultrasound-confirmed L1-2 or L4-5 interspace. Patient-controlled epidural analgesia and breakthrough manual epidural boluses of 10 mL of 0.125% bupivacaine with 50 µg of fentanyl or 8 mL of 2% lidocaine were utilized. Abdominal and perineal pain scores were assessed at 30 and 60 minutes after standardized initiation of epidural analgesia. Pain scores during pushing were assessed after delivery. The primary outcome was the proportion of patients requiring manual boluses and was compared using a χ test. Secondarily, we analyzed the number of boluses given in early (up to 4 hours before delivery) versus late labor using χ tests and the pain scores using Mann-Whitney U tests, with adjustment of P values for multiple testing. We analyzed 148 patients. Overall, the percentage of patients in the low versus high groups who required manual boluses was 46% vs 51% (P = 1.0). For the 56 patients in each group who delivered vaginally, 22 (52%) vs 20 (48%) manual boluses were given to the low epidural group in early versus late labor, compared to 9 (20%) vs 36 (80%) in the high epidural group (P = .014). There was no statistical difference in patient-controlled epidural analgesia requirements or patient satisfaction. Comparing the low versus high groups, the median (interquartile range) pain scores were: 3 (1, 6) vs 0 (0, 2) (P = .013) at 30 minutes and 1 (1, 3) vs 0 (0, 1) (P = .013) at 60 minutes for abdominal pain; 0 (0, 2) vs 1 (1, 3) (P = .36) and 0 (0, 1) vs 1 (1, 3) (P = .014) at these same time points for perineal pain; and 1 (0, 5) vs 0 (0, 3) (P = .9) for abdominal and 2 (0, 5) vs 4 (1, 8) (P = .025) for perineal pain during pushing. The percentage of patients who underwent instrumental delivery was 15% vs 5% (P = .06) for the low versus high group. An L4-5 epidural catheter initially provides less relief of abdominal pain but more relief of perineal labor pain. Patients with an L4-5 catheter require more manual boluses during early labor but less during late labor. The possible association of low epidural catheters with instrumental delivery merits further investigation.


Assessment of service quality of public antiretroviral treatment (ART) clinics in South Africa: a cross-sectional study.
In South Africa the ever increasing demand for antiretroviral treatment (ART) runs the risk of leading to sub-optimal care in public sector ART clinics that are overburdened and under resourced. This study assessed the quality of ART services to identify service areas that require improvement. A cross-sectional study was carried out at 16 of 17 public ART clinics in the target area in greater Pretoria, South Africa. Trained participant observers presented as ART qualifying HIV positive patients that required a visit to assess treatment readiness. They evaluated each facility on five different occasions between June and November 2009, assessing the time it took to get an appointment, the services available and accessed, service quality and the duration of the visit. Services (reception area, clinician's consultation, HIV counselling, pharmacy, nutrition counselling and social worker's assessment) were assessed against performance standards that apply to all clinics. Service quality was expressed as scores for clinic performance (CPS) and service performance (SPS), defined as the percentage of performance standards met per clinic and service area. In most of the clinics (62.5%) participant observers were able to obtain an appointment within one week, although on the day of their visit essential services could not always be accessed. The median CPS of the assessed facilities was 68.5 with four clinics not meeting minimum standards (CPS > 60). The service areas that performed least well were the clinician's consultation (SPS 67.3) and HIV counselling (SPS 70.7). Most notably, clinicians performed a physical examination in only 41.1% of the visits and rarely did a complete TB symptom screening. Counsellors frequently failed to address prevention of HIV transmission. Overall public sector ART clinics in greater Pretoria were easily accessible and their services were of an acceptable quality. However, the time spent at the clinic to complete the services was found to be very long and there was considerable variation in adherence to performance standards within the services, particularly in respect of clinician's consultation and counselling. Clinic management needs to ensure efficient clinic organisation and to improve adherence to performance standards in key service areas.


Analytical State-Average Complete-Active-Space Self-Consistent Field Nonadiabatic Coupling Vectors: Implementation with Density-Fitted Two-Electron Integrals and Application to Conical Intersections.
Analytical state-average complete-active-space self-consistent field derivative (nonadiabatic) coupling vectors are implemented. Existing formulations are modified such that the implementation is compatible with Cholesky-based density fitting of two-electron integrals, which results in efficient calculations especially with large basis sets. Using analytical nonadiabatic coupling vectors, the optimization of conical intersections is implemented within the projected constrained optimization method. The standard description and characterization of conical intersections is reviewed and clarified, and a practical and unambiguous system for their classification and interpretation is put forward. These new tools are subsequently tested and benchmarked for 19 different conical intersections. The accuracy of the derivative coupling vectors is validated, and the information that can be drawn from the proposed characterization is discussed, demonstrating its usefulness.


Use of fecundity measured directly throughout the breeding season to test a source-sink demographic model.
Populations of landbirds (bird species that occupy terrestrial habitats for most of their life cycle) are declining throughout North America (north of Mexico) and Europe, yet little is known about how demography is driving this trend. A recent model of 5 geographically separated populations of Cerulean Warblers (Dendroica cerulea) that was based on within-season sampling of nest survival and fledgling success shows that all populations are sinks (annual reproduction is consistently less than annual adult mortality). I tested this indirect model by directly measuring fecundity (number of female fledglings/female) during the breeding season for 2 years in a Cerulean Warbler population occupying a mature forest in southwestern Michigan (U.S.A.) I determined territories of male birds on the basis of male plumage characters and phases of the nesting cycle (2007) and on uniquely color-banded males (2008). I transferred locations of identified males to topographic maps. I counted all fledglings in territories from May to July each year. The model I tested may apply only to single-brooded species; therefore, I searched the literature to estimate the percentage of single-brooded species in North America. The breeding season of Cerulean Warblers was short- nearly all nests were initiated from mid-May to late June. Nest predation and brood parasitism were primary and rare causes of nest failure, respectively. Significantly fewer Cerulean Warblers fledged from parasitized than from nonparasitized nests. Fledgling survival required to maintain the population size was well above previously published values for Neotropical migrants. Single-brooded species comprise 62% of North American breeding bird species for which the number of broods per year is known; I believe my results may apply to these species. The consistency between identification of populations as sources or sinks on the basis of either model estimates or direct measurements suggests that a demographic model relying on within-season sampling of fecundity is adequate to determine population status of single-brooded avian populations. In addition, on the basis of results of previous studies, annual adult survival rate of the Cerulean Warbler is typical of parulid warblers that are not declining. Thus, low fecundity, here determined with different quantitative methods, can drive status of landbird species with high-observed survival.


Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women.
Estrogen deficiency may account for lower circulating GH and insulin-like growth factor I (IGF-I) concentrations in the menopause. Since the liver is the major source of circulating IGF-I and oral estrogens have nonphysiological effects on hepatic function, we have compared GH secretion over 24 h from 20 min sampling and serum IGF-I levels in premenopausal women (n = 7, follicular phase) and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (EE, 20 micrograms daily; n = 7) or transdermal 17 beta-estradiol (E2, 100 micrograms patches applied twice weekly; n = 7). The extent of GH binding to its serum binding protein was also examined by measuring the percent specific binding of [125I] GH in serum. Mean 24-h serum GH and serum IGF-I were significantly lower (P less than 0.05) in postmenopausal than in premenopausal women. Oral and transdermal estrogen therapy resulted in a comparable degree of gonadotropin suppression. Oral EE treatment increased mean 24-h serum GH (2.0 +/- 0.4 to 7.0 +/- 0.6 mIU/L, P less than 0.0005) and mean pulse amplitude (5.3 +/- 1.2 to 11.2 +/- 2.5 mIU/L, P less than 0.01) but significantly reduced circulating IGF-I (0.70 +/- 0.09 to 0.47 +/- 0.04 U/mL, P less than 0.02) levels. Oral EE increased the percent specific binding of [125I]GH (22.0 +/- 1.6 to 32.0 +/- 1.9%, P less than 0.0005), however the derived mean 24-h free serum GH concentrations were significantly higher (P less than 0.0005) after treatment. By contrast, transdermal E2 administration, which restored circulating E2 concentrations to the midfollicular range, increased circulating IGF-I (0.86 +/- 0.15 to 1.10 +/- 0.14 U/mL, P less than 0.005) to levels that were not significantly different from those of premenopausal women (1.41 +/- 0.21 U/mL). This was not accompanied by changes in 24-h GH secretion or the percent specific binding of [125I]GH in serum. The route of administration is a major determinant of the effects of exogenous estrogens on the GH/IGF-I axis. Oral estrogen administration inhibits hepatic IGF-I synthesis and increases GH secretion through reduced feedback inhibition. Reduced GH secretion in the menopause is not explained by estrogen deficiency since GH secretion is not restored by the attainment of physiological E2 concentrations using the transdermal route. The contrasting route dependent IGF-I responses have important implications for the long-term benefit of hormone replacement therapy in the menopause.


Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex.
We investigate self-sustaining stable states (attractors) in networks of integrate-and-fire neurons. First, we study the stability of spontaneous activity in an unstructured network. It is shown that the stochastic background activity, of 1-5 spikes/s, is unstable if all neurons are excitatory. On the other hand, spontaneous activity becomes self-stabilizing in presence of local inhibition, given reasonable values of the parameters of the network. Second, in a network sustaining physiological spontaneous rates, we study the effect of learning in a local module, expressed in synaptic modifications in specific populations of synapses. We find that if the average synaptic potentiation (LTP) is too low, no stimulus specific activity manifests itself in the delay period. Instead, following the presentation and removal of any stimulus there is, in the local module, a delay activity in which all neurons selective (responding visually) to any of the stimuli presented for learning have rates which gradually increase with the amplitude of synaptic potentiation. When the average LTP increases beyond a critical value, specific local attractors (stable states) appear abruptly against the background of the global uniform spontaneous attractor. In this case the local module has two available types of collective delay activity: if the stimulus is unfamiliar, the activity is spontaneous; if it is similar to a learned stimulus, delay activity is selective. These new attractors reflect the synaptic structure developed during learning. In each of them a small population of neurons have elevated rates, which depend on the strength of LTP. The remaining neurons of the module have their activity at spontaneous rates. The predictions made in this paper could be checked by single unit recordings in delayed response experiments.


Comparative analysis of nutrition data from national, household, and individual levels: results from a WHO-CINDI collaborative project in Canada, Finland, Poland, and Spain.
This project determined to what extent data on diet and nutrition, which were collected in a non-uniform manner, could be harmonised and pooled for international and national comparison. Direct comparisons of dietary data between studies were made using food balance sheets (FBS), household budget surveys (HBS), and individual dietary data (IDS); comparisons were also made within countries. Differences in study design and methodological approaches were taken into consideration. Data from research projects from the following four World Health Organisation (WHO) Countrywide Integrated Noncommunicable Disease Intervention (CINDI) countries were included-Canada, Finland, Poland, and Spain. FBS overestimated food consumption and nutrient intake compared to IDS. Results between HBS and IDS were quite similar, except for fish, meat, pulses and vegetables, which were underestimated by HBS, and sugar and honey and cereals, which were overestimated. Percentages of energy from fat, carbohydrates and proteins were higher when estimated from FBS, HBS, and IDS respectively. Results suggest that estimations from these three sources of dietary data are difficult to compare because they are measuring different levels of dietary information. The understanding of their relations may be important in formulating and evaluating a nutrition policy.


Repaired and open atrial septal defects type II in adulthood: an epidemiological study of a large European cohort.
There is a lack of evidence regarding treatment options for adults with an atrial septal defect (ASD) who present with an open defect or with sequelae after closure of the defect. The aim of this study was to describe the clinical characteristics and treatment of a large cohort of adult patients born with an ASD type II. Data on the clinical characteristics of 882 ASD II patients (mean follow-up of 4.2 years) included in the Euro Heart Survey on adult congenital heart disease were analysed. At baseline, the defects of 377 patients (mean age 39.2 (16.1) years; 65% females) had been closed, leaving 505 patients (mean age 41.1 (16.4) years; 68% females) with an open ASD. Hemodynamic abnormalities were more prevalent among patients with an open compared to those with a closed defect at baseline: pulmonary arterial hypertension 35% versus 13%; right ventricular (RV) dysfunction 31% versus 8%; and severe RV volume overload 18% versus 1% (all P-values<0.001). These prevalences increased with age, but hemodynamic parameters remained stable during follow-up in nearly all patients with a small defect. Also functional limitations were more common in those with open defects at baseline compared to those with closed defects (54% versus 25%). There was no difference in the prevalence of arrhythmia's. The best independent predictors of functional limitations appeared to be PAH (odds ratio 25.2 (5.8-109.6); P<0.001)) and RV volume overload (odds ratio 2.3 (1.5-3.4; P<0.001)) in a multivariable model. During follow-up, 9 patients died and in 294 patients the defect was closed, in 180 patients surgically, and in 114 patients by device. Among the latter group there were relatively more females (78% vs 66%; P=0.035). In the surgically closed group defects were more "severe". There were substantial differences according to country in the relative frequency of device closure versus surgical closure, as well as the size and hemodynamic severity of the defects closed. The data from this study provide a cross-section of the kind of adult patients with an ASD that are seen at outpatient clinics for adult congenital heart disease throughout Europe. Taken together, non-operated patients fared significantly worse in all aspects of hemodynamics studied than the patients whose defects had been closed. In moderate or large defects, when not-operated, clinical parameters tend to worsen with time, and closure of such a defect-the sooner the better-seems always to be the preferred treatment option. In the majority of small defects, operation is not necessarily indicated.


Contrasting thermal strategies of montane Neotropical bats at high elevations.
In the Neotropics, captive vespertilionid bats substantially reduce their metabolic rate at low ambient temperatures, similar to their temperate counterparts, whereas the ability of phyllostomids to lower metabolic rate seems to be more limited, even in mountain species. Nevertheless, field data on the thermal behaviour of syntopic individuals from these two families is lacking. Consequently, we aimed to test whether torpor was more common and deeper in vesper bats compared to leaf-nosed bats by studying skin temperature (Tsk) variation in individuals experiencing the same environmental conditions at a mountain area. Bats experienced ambient temperatures below 15 °C. Average Tsk was 10 °C in Myotis oxyotus gardneri (Vespertilionidae) during the day, while Sturnira burtonlimi (Phyllostomidae) regulated diurnal Tsk above 30 °C. Constant food availability may explain why diurnal Sturnira burtonlimi pay the high energetic cost required to remain normothermic and to defend a wide Ta-Tsk gap but further studies are needed to elucidate additional strategies that may be employed by these bats to reduce the energetic demands of normothermy. Our study shows that the contrasting thermal strategies and torpor use adopted by vespertilionid insectivores and phyllostomid frugivores in captive settings also occur in free-ranging conditions, thus providing a basis to develop further studies with predictions more accurately rooted in field data.


High temperature-induced proteomic and metabolomic profiles of a thermophilic Bacillus manusensis isolated from the deep-sea hydrothermal field of Manus Basin.
Thermophiles are organisms that grow optimally at 50 °C-80 °C and studies on the survival mechanisms of thermophiles have drawn great attention. Bacillus manusensis S50-6 is the type strain of a new thermophilic species isolated from hydrothermal vent in Manus Basin. In this study, we examined the growth and global responses of S50-6 to high temperature on molecular level using multi-omics method (genomics, proteomics, and metabolomics). S50-6 grew optimally at 50 °C (Favorable, F) and poorly at 65 °C (Non-Favorable, NF); it formed spores at F but not at NF condition. At NF condition, S50-6 formed long filaments containing undivided cells. A total of 1621 proteins were identified at F and NF conditions, and 613 proteins were differentially expressed between F and NF. At NF condition, proteins of glycolysis, rRNA mature and modification, and DNA/protein repair were up-regulated, whereas proteins of sporulation and amino acid/nucleotide metabolism were down-regulated. Consistently, many metabolites associated with amino acid and nucleotide metabolic processes were down-regulated at NF condition. Our results revealed molecular strategies of deep-sea B. manusensis to survive at unfavorable high temperature and provided new insights into the thermotolerant mechanisms of thermophiles. SIGNIFICANCE: In this study, we systematically characterized the genomic, proteomic and metabolomic profiles of a thermophilic deep-sea Bacillus manusensis under different temperatures. Based on these analysis, we propose a model delineating the global responses of B. manusensis to unfavorable high temperature. Under unfavorable high temperature, glycolysis is a more important energy supply pathway; protein synthesis is subjected to more stringent regulation by increased tRNA modification; protein and DNA repair associated proteins are enhanced in production to promote heat survival. In contrast, energy-costing pathways, such as sporulation, are repressed, and basic metabolic pathways, such as amino acid and nucleotide metabolisms, are slowed down. Our results provide new insights into the thermotolerant mechanisms of thermophilic Bacillus.


Rapid direct analysis of river water and machine learning assisted suspect screening of emerging contaminants in passive sampler extracts.
A novel and rapid approach to characterise the occurrence of contaminants of emerging concern (CECs) in river water is presented using multi-residue targeted analysis and machine learning-assisted in silico suspect screening of passive sampler extracts. Passive samplers (Chemcatcher®) configured with hydrophilic-lipophilic balanced (HLB) sorbents were deployed in the Central London region of the tidal River Thames (UK) catchment in winter and summer campaigns in 2018 and 2019. Extracts were analysed by; (a) a rapid 5.5 min direct injection targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for 164 CECs and (b) a full-scan LC coupled to quadrupole time of flight mass spectrometry (QTOF-MS) method using data-independent acquisition over 15 min. From targeted analysis of grab water samples, a total of 33 pharmaceuticals, illicit drugs, drug metabolites, personal care products and pesticides (including several EU Watch-List chemicals) were identified, and mean concentrations determined at 40 ± 37 ng L-1. For targeted analysis of passive sampler extracts, 65 unique compounds were detected with differences observed between summer and winter campaigns. For suspect screening, 59 additional compounds were shortlisted based on mass spectral database matching, followed by machine learning-assisted retention time prediction. Many of these included additional pharmaceuticals and pesticides, but also new metabolites and industrial chemicals. The novelty in this approach lies in the convenience of using passive samplers together with machine learning-assisted chemical analysis methods for rapid, time-integrated catchment monitoring of CECs.


Psychiatric disorders in children and adolescents 24 months after mild traumatic brain injury.
This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.


Current changes in the epidemiology of fall-related injuries in Al Ain City, United Arab Emirates.
Falls in the Gulf countries are the second most common cause of injuries. The United Arab Emirates government implemented various preventive measures to decrease injuries in the country. We aimed to evaluate the changes in the epidemiology of fall-related injuries in Al-Ain City over the last decade. Data of hospitalized patients who presented with fall-related injuries to the Al-Ain Hospital during the two periods of March 2003 to March 2006 and January 2014 to December 2017 were compared. This included patients' demographics, mechanism, location, anatomical distribution and parameters related to injury severity. Non-parametric tests were used for the statistical analysis. 882 in the first and 1358 patients in the second period were studied. The incidence of falls decreased by 30.5% over ten years. The number of elderly, female patients, and UAE nationals increased, (p < 0.001, p = 0.004, and p < 0.001). Falls from height decreased by 32.5% (p < 0.001) while fall on the same level increased by 22.5% (p < 0.001). Fall-related injuries at home have increased significantly by 22.6% (p <0.001), while falls in workplaces decreased by 24.4% (p <0.001). Our study showed that the overall incidence of falls decreased compared to a decade ago. The preventive measures were effective in reducing falls from height and workplace injuries. Future preventive measures should target falls at the same level and homes.


Globally consistent reef size spectra integrating fishes and invertebrates.
The frequency distribution of individual body sizes in animal communities (i.e. the size spectrum) provides powerful insights for understanding the energy flux through food webs. However, studies of size spectra in rocky and coral reef communities typically focus only on fishes or invertebrates due to taxonomic and data constraints, and consequently ignore energy pathways involving the full range of macroscopic consumer taxa. We analyse size spectra with co-located fish and mobile macroinvertebrate data from 3369 reef sites worldwide, specifically focusing on how the addition of invertebrate data alters patterns. The inclusion of invertebrates steepens the size spectrum, more so in temperate regions, resulting in a consistent size spectrum slope across latitudes, and bringing slopes closer to theoretical expectations based on energy flow through the system. These results highlight the importance of understanding contributions of both invertebrates and fishes to reef food webs worldwide.


Understanding Implementation Challenges to Genetic Testing for Familial Hypercholesterolemia in the United States.
Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known pathogenic and likely pathogenic variations in FH-associated genes. Key organizations, such as the Centers for Disease Control and Prevention (CDC), American Heart Association (AHA), FH Foundation, and National Lipid Association (NLA), have recognized the clinical utility of FH genetic testing. However, FH genetic testing is underutilized in clinical practice in the US for reasons that are underexplored through the lens of implementation science. In this commentary, we discuss seven key implementation challenges that must be overcome to strengthen the clinical adoption of FH genetic testing in the US. These implementation challenges center on evidence of cost-effectiveness, navigating patient and provider preferences and concerns, gender and ethnic diversity and representation in genetic testing, and establishing clinical consensus around FH genetic testing based on the latest and most relevant research findings. Overcoming these implementation challenges is imperative to the mission of reducing CVD risk in the US.


Fast and accurate multivariate Gaussian modeling of protein families: predicting residue contacts and protein-interaction partners.
In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code.


A self-assembling peptide acting as an immune adjuvant.
The development of vaccines and other immunotherapies has been complicated by heterogeneous antigen display and the use of incompletely defined immune adjuvants with complex mechanisms of action. We have observed strong antibody responses in mice without the coadministration of any additional adjuvant by noncovalently assembling a T and B cell epitope peptide into nanofibers using a short C-terminal peptide extension. Self-assembling peptides have been explored recently as scaffolds for tissue engineering and regenerative medicine, but our results indicate that these materials may also be useful as chemically defined adjuvants. In physiological conditions, these peptides self-assembled into long, unbranched fibrils that displayed the epitope on their surfaces. IgG1, IgG2a, and IgG3 were raised against epitope-bearing fibrils in levels similar to the epitope peptide delivered in complete Freund's adjuvant (CFA), and IgM production was even greater for the self-assembled epitope. This response was dependent on self-assembly, and the self-assembling sequence was not immunogenic by itself, even when delivered in CFA. Undetectable levels of interferon-gamma, IL-2, and IL-4 in cultures of peptide-challenged splenocytes from immunized mice suggested that the antibody responses did not involve significant T cell help.


Does volume matter? The effect of trauma surgeons' caseload on mortality.
Evidence suggests that trauma centers treating high volumes of severely injured patients produce lower mortality rates than those with low volumes. However, the effect of individual surgeons' trauma caseload on outcomes has not been studied. This study compares outcomes between high-volume (HV) trauma surgeons admitting many patients with high injury severity, and low-volume (LV) surgeons treating fewer critical patients per year. All trauma patients admitted to a large Level I trauma center over a 12-year period were assigned to either the HV or LV group, depending on the yearly volume of their admitting surgeon. Surgeons treating > 35 severely injured (Injury Severity Score > 15) patients per year were considered HV. Student's t test and chi2 analysis were used to test comparability of LV and HV patient groups and to compare mortality rates. Mortality rates of HV and LV surgeons' patients were compared in six injury patterns selected to represent moderate to severe injury. TRISS methodology (z score) was also used to assess outcomes in the two groups. The inherent bias of the TRISS method in comparing trauma outcomes was minimized by the homogeneity of the studied patient population. A total of 16,481 patients were admitted to HV surgeons, and 4,214 patients were admitted to LV surgeons. In all subgroups, HV and LV patients were similar regarding age, sex, physiologic status at admission, injury pattern, and injury severity. Mortality rates for HV and LV surgeons were not significantly different between the two groups in any injury pattern. The z score was 1.88 in the HV patient group versus 0.47 in the LV group. Within a single institution, mortality rates for patients treated by surgeons admitting many severely injured patients were not significantly different from low-volume surgeons' patients, although there was a trend toward higher mortality in the less active surgeons' patients in some subgroups.


A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes.
The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.


Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study.
Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population-based studies have quantified and compared cancer risks according to graft type and with long-term follow-up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow-up of 93,432 person-years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIR(cancer excl SCC) 2.4 (95% CI, 2.2-2.5); SIR(SCC) 121 (95% CI, 116-127). Cancer risks were most increased among heart and/or lung recipients SIR(cancer excl SCC) 3.3 (95% CI, 2.8-4.0); SIR(SCC) 198 (95% CI, 174-224), followed by kidney SIR(cancer excl SCC) 2.3 (95% CI, 2.1-2.4); SIR(SCC) 121 (95% CI, 116-127) and liver recipients SIR(cancer excl SCC) 2.3 (95% CI, 1.9-2.8); SIR(SCC) 32 (95% CI, 24-42). During follow-up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post-transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.


The nurse's load: early-life exposure to brood-rearing affects behavior and lifespan in honey bees (Apis mellifera).
Long-lived honey bees (Apis mellifera) develop in fall. This pattern may be explained by reduced nurse loads. When the amount of brood in colonies declines as a function of adverse foraging conditions, adult bees build up surplus nutrient stores that include vitellogenin, a behavioral affector protein that also can increase lifespan. Although the seasonal reduction in exposure to nursing tasks predictably results in vitellogenin accumulation, the assumption that long-lived adults thereby develop is confounded by a concomitant decline in foraging effort. Foraging activity reduces lifespan, and is influenced by colony resource consumption, brood pheromones, availability of nectar and pollen, and weather. Here, we perform the first controlled experiment where the nursing environment of pre-foraging sister bees was set to vary, while their foraging environment later was set to be the same. We measure vitellogenin, age at foraging onset and lifespan. We establish that reduced brood-rearing increases vitellogenin levels, and delays foraging onset and death. Longevity is largely explained by the effect of nursing on the onset of foraging behavior, but is also influenced by the level of brood-rearing independent of behavioral change. Our findings are consistent with the roles of vitellogenin in regulation of honey bee behavior and lifespan.


The potential of a self-assessment tool to identify healthcare professionals' strengths and areas in need of professional development to aid effective facilitation of group-based, person-centered diabetes education.
Healthcare professionals' person-centered communication skills are pivotal for successful group-based diabetes education. However, healthcare professionals are often insufficiently equipped to facilitate person-centeredness and many have never received post-graduate training. Currently, assessing professionals' skills in conducting group-based, person-centered diabetes education primarily focus on experts measuring and coding skills on various scales. However, learner-centered approaches such as adequate self-reflective tools have been shown to emphasize professional autonomy and promote engagement. The aim of this study was to explore the potential of a self-assessment tool to identify healthcare professionals' strengths and areas in need of professional development to aid effective facilitation of group-based, person-centered diabetes education. The study entails of two components: 1) Field observations of five different educational settings including 49 persons with diabetes and 13 healthcare professionals, followed by interviews with 5 healthcare professionals and 28 persons with type 2 diabetes. 2) One professional development workshop involving 14 healthcare professionals. Healthcare professionals were asked to assess their person-centered communication skills using a self-assessment tool based on challenges and skills related to four educator roles: Embracer, Facilitator, Translator, and Initiator. Data were analyzed by hermeneutic analysis. Theories derived from theoretical model 'The Health Education Juggler' and techniques from 'Motivational Interviewing in Groups' were used as a framework to analyze data. Subsequently, the analysis from the field notes and interview transcript were compared with healthcare professionals' self-assessments of strengths and areas in need to effectively facilitate group-based, person-centered diabetes education. Healthcare professionals self-assessed the Translator and the Embracer to be the two most skilled roles whereas the Facilitator and the Initiator were identified to be the most challenged roles. Self-assessments corresponded to observations of professional skills in educational programs and were confirmed in the interviews. Healthcare professionals self-assessed the same professional skills as observed in practice. Thus, a tool to self-assess professional skills in facilitating group-based diabetes education seems to be useful as a starting point to promote self-reflections and identification of healthcare professionals' strengths and areas of need of professional development.


The effect of Wolbachia on dengue dynamics in the presence of two serotypes of dengue: symmetric and asymmetric epidemiological characteristics.
An innovative strategy to reduce dengue transmission uses the bacterium Wolbachia. We analysed the effects of Wolbachia on dengue transmission dynamics in the presence of two serotypes of dengue using a mathematical model, allowing for differences in the epidemiological characteristics of the serotypes. We found that Wolbachia has a greater effect on secondary infections than on primary infections across a range of epidemiological characteristics. If one serotype is more transmissible than the other, it will dominate primary infections and Wolbachia will be less effective at reducing secondary infections of either serotype. Differences in the antibody-dependent enhancement of the two serotypes have considerably less effect on the benefits of Wolbachia than differences in transmission probability. Even if the antibody-dependent enhancement rate is high, Wolbachia is still effective in reducing dengue. Our findings suggest that Wolbachia will be effective in the presence of more than one serotype of dengue; however, a better understanding of serotype-specific differences in transmission probability may be needed to optimize delivery of a Wolbachia intervention.