The Views of Homeless People and Health Care Professionals on Palliative Care and the Desirability of Setting Up a Consultation Service: A Focus Group Study.
Palliative care for homeless people is often given late, if at all. Professionals in both palliative care and shelter care are often insufficiently equipped to provide this complex care. To provide insights into the palliative care experiences of professionals and homeless people, including barriers and facilitators to care, and to investigate whether a consultative function can help improve palliative care for homeless people. Six focus groups were included; four with professionals (n = 19) and two with severely ill homeless people (n = 15). Professionals were sampled purposively in organizations providing (palliative) care to the homeless. Homeless people were recruited by opportunity sampling. Palliative care for homeless people is especially complex and differs substantially from regular palliative care. It differs greatly among professionals, institutions, and cities. Homeless people get less autonomy than they would like. Homeless people and professionals have different perceptions of the care provided. Trusting relationships between professionals and homeless people is essential and easily accessible, and flexible care is needed. Consultation, in particular involving exchange of expertise between professionals, can provide added value to professionals. Homeless people consider consultation primarily as an opportunity to train professionals to show more understanding, provide tailored palliative care, and enhance professional collaboration. The local situation, characteristics of a consultant, and role of a consultant in providing information and education must be considered when developing the consultation process. Consultation can play an important role in improving palliative care by linking disciplines, providing support to professionals and appropriate palliative care to homeless people.


Receptiveness to advice, cognitive ability, and technology adoption☆.
We construct a model of technology adoption with agents differing on two dimensions: their cognitive ability and their receptiveness to advice. While cognitive ability unambiguously speeds adoption, receptiveness to advice may speed adoption for individuals with low cognitive ability, but slow adoption for individuals with high cognitive ability. We conduct economic experiments measuring US farmers' cognitive ability and receptiveness to advice and examine how these characteristics impact their speed of adoption of genetically modified (GM) corn seeds. The empirical analysis shows that early adopters are those who are both quite able cognitively and not receptive to advice.


Effects of dexmedetomidine on succinylcholine-induced myalgia in the early postoperative period.
To determine the effects of dexmedetomidine on the incidence of fasciculation and myalgia, and to evaluate changes in creatine kinase levels due to succinylcholine administration. Sixty patients undergoing direct laryngoscopy were enrolled in this study carried out in the Department of Anesthesiology and Reanimation, Hacettepe University, Ankara, Turkey between January and March 2010. Patients were allocated blindly to 3 anesthesiologists. In the dexmedetomidine group (group D) (n=30), dexmedetomidine 1ug/kg was administered intravenously over 10 minutes before the intubation. In the control group (group C) (n=30), the same volume of normal saline was administered. Laryngoscopy was performed one minute after administration of succinylcholine. Dexmedetomidine infusion was continued until the end of surgery. Fasciculation and myalgia at the postoperative thirtieth minute, and creatine kinase levels before the induction of anesthesia and at the postoperative 24th hour, and adequacy of relaxation for intubation were recorded. The severity and incidence of fasciculation were better in group D than group C (p=0.025). Intubating conditions were better in the dexmedetomidine group (p=0.011). At the thirtieth minute, the incidence and severity of myalgia were significantly higher in group C (p=0.014). Postoperative creatine kinase levels increased significantly compared with their base-line levels in both groups (p=0.022 in group D and p=0.017 in group C). Creatine kinase level elevation was higher in group C (p=0.03). Dexmedetomidine infusion before and after succinylcholine administration may be useful in diminishing the incidence of succinylcholine-induced myalgia in the early postoperative period. Routine use of dexmedetomidine cannot be recommended, but further research is needed with a larger number of patients.


Sufficient catheter length for pneumothorax needle decompression: a meta-analysis.
Needle thoracostomy is the prehospital treatment for tension pneumothorax. Sufficient catheter length is necessary for procedural success. The authors of this study determined minimum catheter length needed for procedural success on a percentile basis. A meta-analysis of existing studies was conducted. A Medline search was performed using the search terms: needle decompression, needle thoracentesis, chest decompression, pneumothorax decompression, needle thoracostomy, and tension pneumothorax. Studies were included if they published a sample size, mean chest wall thickness, and a standard deviation or confidence interval. A PubMed search was performed in a similar fashion. Sample size, mean chest wall thickness, and standard deviation were found or calculated for each study. Data were combined to create a pooled dataset. Normal distribution of data was assumed. Procedural success was defined as catheter length being equal to or greater than the chest wall thickness. The Medline and PubMed searches yielded 773 unique studies; all study abstracts were reviewed for possible inclusion. Eighteen papers were identified for full manuscript review. Thirteen studies met all inclusion criteria and were included in the analysis. Pooled sample statistics were: n=2,558; mean=4.19 cm; and SD=1.37 cm. Minimum catheter length needed for success at the 95th percentile for chest wall size was found to be 6.44 cm. A catheter of at least 6.44 cm in length would be required to ensure that 95% of the patients in this pooled sample would have penetration of the pleural space at the site of needle decompression, and therefore, a successful procedure. These findings represent Level III evidence.


Proton tunneling in low dimensional cesium silicate LDS-1.
In low dimensional cesium silicate LDS-1 (monoclinic phase of CsHSi2O5), anomalous infrared absorption bands observed at 93, 155, 1210, and 1220 cm(-1) are assigned to the vibrational mode of protons, which contribute to the strong hydrogen bonding between terminal oxygen atoms of silicate chain (O-O distance = 2.45 Å). The integrated absorbance (oscillator strength) for those modes is drastically enhanced at low temperatures. The analysis of integrated absorbance employing two different anharmonic double-minimum potentials makes clear that proton tunneling through the potential barrier yields an energy splitting of the ground state. The absorption bands at 93 and 155 cm(-1), which correspond to the different vibrational modes of protons, are attributed to the optical transition between the splitting levels (excitation from the ground state (n = 0) to the first excited state (n = 1)). Moreover, the absorption bands at 1210 and 1220 cm(-1) are identified as the optical transition from the ground state (n = 0) to the third excited state (n = 3). Weak Coulomb interactions in between the adjacent protons generate two types of vibrational modes: symmetric mode (93 and 1210 cm(-1)) and asymmetric mode (155 and 1220 cm(-1)). The broad absorption at 100-600 cm(-1) reveals an emergence of collective mode due to the vibration of silicate chain coupled not only with the local oscillation of Cs(+) but also with the proton oscillation relevant to the second excited state (n = 2).


Use of mizoribine as a rescue drug for steroid-resistant pediatric IgA nephropathy.
Recent clinical trials have shown a beneficial effect of mizoribine (Miz), an immunosuppressive drug, in the treatment of new-onset pediatric IgA nephropathy (IgAN). In this study, we evaluated the efficacy of Miz treatment in three children with established steroid-resistant IgAN. The patients had IgAN featuring persistent proteinuria and diffuse mesangial proliferation and had failed to respond to 2 years of treatment with prednisolone. Based upon the second biopsy results, patients were given methylprednisolone (mPSL) pulse therapy that induced a transient reduction in proteinuria, which was reversed when the mPSL dose was tapered. Miz therapy was then instigated in place of pulse mPSL. All three patients showed a substantial reduction in proteinuria and resolution of hematuria within 5 months. A follow-up biopsy in two of the patients showed a substantial reduction in the severity of glomerular lesions and a decrease in the number of activated macrophages. In conclusion, Miz therapy was found to be a safe and effective therapy in three cases of steroid-resistant pediatric IgAN. The ability of Miz to reduce the number of activated macrophages may be an important mechanism by which this drug ameliorated renal disease in these patients.


Common disorders are quantitative traits.
After drifting apart for 100 years, the two worlds of genetics - quantitative genetics and molecular genetics - are finally coming together in genome-wide association (GWA) research, which shows that the heritability of complex traits and common disorders is due to multiple genes of small effect size. We highlight a polygenic framework, supported by recent GWA research, in which qualitative disorders can be interpreted simply as being the extremes of quantitative dimensions. Research that focuses on quantitative traits - including the low and high ends of normal distributions - could have far-reaching implications for the diagnosis, treatment and prevention of the problematic extremes of these traits.


The timing of maternal depressive symptoms and mothers' parenting practices with young children: implications for pediatric practice.
The prevalence of maternal depressive symptoms and its associated consequences on parental behaviors, child health, and development are well documented. Researchers have called for additional work to investigate the effects of the timing of maternal depressive symptoms at various stages in the development of the young child on the emergence of developmentally appropriate parenting practices. For clinicians, data are limited about when or how often to screen for maternal depressive symptoms or how to target anticipatory guidance to address parental needs. We sought to determine whether concurrent maternal depressive symptoms have a greater effect than earlier depressive symptoms on the emergence of maternal parenting practices at 30 to 33 months in 3 important domains of child safety, development, and discipline. Secondary analyses from the Healthy Steps National Evaluation were conducted for this study. Data sources included a self-administered enrollment questionnaire and computer-assisted telephone interviews with the mother when the Healthy Steps children were 2 to 4 and 30 to 33 months of age. The 30- to 33-month interview provided information about 4 safety practices (ie, always uses car seat, has electric outlet covers, has safety latches on cabinets, and lowered temperature on the water heater), 6 child development practices (ie, talks daily to child while working, plays daily with child, reads daily to child, limits child television and video watching to <2 hours a day, follows > or = 3 daily routines, and being more nurturing), and 3 discipline practices (ie, uses more reasoning, uses more harsh punishment, and ever slapped child on the face or spanked the child with an object). The parenting practices were selected based on evidence of their importance for child health and development, near complete data, and sample variability. The discipline practices were constructed from the Parental Response to Misbehavior Scale. Maternal depressive symptoms were assessed using a 14-item modified version of the Center for Epidemiologic Studies-Depression Scale. Multiple logistic regression models estimated the effect of depressive symptoms on parenting practices, adjusted for baseline demographic characteristics, Healthy Steps participation, and site. No significant interactions were found when testing analytic models with dummy variables for depressive symptoms at 2 to 4 months only, 30 to 33 months only, and at both times; reported models do not include interaction terms. We report main effects of depressive symptoms at 2 to 4 and 30 to 33 months when both are included in the model. Of 5565 families, 3412 mothers (61%) completed 2- to 4- and 30- to 33-month interviews and provided Center for Epidemiologic Studies-Depression Scale data at both times. Mothers with depressive symptoms at 2 to 4 months had reduced odds of using car seats, lowering the water heater temperature, and playing with the child at 30 to 33 months. Mothers with concurrent depressive symptoms had reduced odds of using electric outlet covers, using safety latches, talking with the child, limiting television or video watching, following daily routines, and being more nurturing. Mothers with concurrent depressive symptoms had increased odds of using harsh punishment and of slapping the child on the face or spanking with an object. The study findings suggest that concurrent maternal depressive symptoms have stronger relations than earlier depressive symptoms, with mothers not initiating recommended age-appropriate safety and child development practices and also using harsh discipline practices for toddlers. Our findings, however, also suggest that for parenting practices that are likely to be established early in the life of the child, it may be reasonable that mothers with early depressive symptoms may continue to affect use of those practices by mothers. The results of our study underscore the importance of clinicians screening for maternal depressive symptoms during the toddler period, as well as the early postpartum period, because these symptoms can appear later independent of earlier screening results. Providing periodic depressive symptom screening of the mothers of young patients has the potential to improve clinician capacity to provide timely and tailored anticipatory guidance about important parenting practices, as well as to make appropriate referrals.


The cancer rehabilitation journey: barriers to and facilitators of exercise among patients with cancer-related fatigue.
Despite the evidence to support exercise as an effective management strategy for patients with cancer-related fatigue (CRF), many of the general cancer population are sedentary. The aim of this study was to explore the barriers to and facilitators of exercise among a mixed sample of patients with CRF. An exploratory, descriptive, qualitative design was used. Purposive sampling methods were used to recruit patients with CRF who were representative of the cancer trajectory, that is, survivors of cancer and patients in palliative care who were recently diagnosed and undergoing treatment. Focus group discussions were transcribed verbatim and analyzed using a grounded theory approach. Lower-level concepts were identified and ordered into subcategories. Related subcategories then were grouped to form the main categories, which were linked to the core category. Five focus groups were conducted with 26 participants. Within the core category of the cancer rehabilitation journey were 3 main categories: (1) exercise barriers, (2) exercise facilitators, and (3) motivators of exercise. Exercise barriers were mainly related to treatment side effects, particularly fatigue. Fatigue was associated with additional barriers such as physical deconditioning, social isolation, and the difficulty of making exercise a routine. Environmental factors and the timing of exercise initiation also were barriers. Exercise facilitators included an exercise program being group-based, supervised, individually tailored, and gradually progressed. Exercise motivators were related to perceived exercise benefits. Individuals with CRF have numerous barriers to exercise, both during and following treatment. The exercise facilitators identified in this study provide solutions to these barriers and may assist with the uptake and maintenance of exercise programs. These findings will aid physical therapists in designing appropriate exercise programs for patients with CRF.


Amnesia: a disconnection syndrome?
An attempt is made to account for the ability of severely amnesic patients to learn and retain certain tasks but not others. The hypothesis is advanced that the amnesic subject can show learning through facilitation by repetition or of simple S-R relationships not requiring cognitive mediation. Three examinations are reported. The first demonstrates that the amnesic subjects have adequate speed of access to semantic and phonological knowledge and show the same degree of improvement on retesting as controls. The second and third experiments examine different degrees of cognitive mediation in paired-associate learning. Amnesic subjects are differentially impaired relative to controls on "distant" pairs and on those that, by hypothesis, would benefit from cognitive mediation. The results are discussed in terms of a disconnection syndrome. It is suggested that at the functional level, a "cognitive mediational memory system" and a semantic memory system are disconnected in the amnesic patient. Neuropathological evidence suggests that temporal lobe and frontal lobe structures are disconnected by pathways in the fornix-mammillary body route.


Susceptibility contrast by echo shifting in spatially encoded single-scan MRI.
To overcome the effects of static field inhomogeneities, single-scan hybrid imaging techniques that use k-space encoding in one direction and spatial encoding in the other have been shown to be superior to traditional imaging techniques based on full k-space encoding. Like traditional imaging methods, hybrid methods can be implemented in different ways that favor different sources of contrast. So far, little attention appears to have been paid to these aspects. By modifying an established hybrid imaging sequence called Rapid Acquisition by Sequential Excitation and Refocusing (RASER) so as to obtain Echo-Shifted RASER sequences, we show that by shifting spin echoes one can tune the contrast due to inhomogeneous T decay.


Alternative halogenated flame retardants (AHFRs) in green mussels from the south China sea.
Restrictions of legacy brominated flame retardants, such as polybrominated diphenyl ether (PBDE) and polybrominated biphenyl (PBB), have resulted in increased usage of alternative halogenated flame retardants (AHFRs). Consequently, AHFRs contamination has caused a major concern in the scientific community. However, there is limited information on their presence in marine mussels. In this study, we investigated the occurrence and distribution of polybrominated biphenyls (PBBs), AHFRs and dehalogenated products in green mussels collected from 22 locations in the northern South China Sea (SCS). Our results revealed that ∑AHFRs were ubiquitous in green mussels with concentrations in the range of 1.08-7.71 ng/g lipid weight (lw). Among target AHFRs, hexabromobenzene (HBB), decabromodiphenyl (DBDPE) and dechlorane plus (DP) were predominant with their mean values of 1.19, 1.00 and 0.82 ng/g lw, respectively. There were negligible stereoisomer enrichments of DP in green mussels based on fanti values, indicating a limited bioaccumulation and metabolism of DP in green mussels. In comparison with other locations, concentrations of the AHFRs in green mussels determined here were at moderate levels. Additionally, there were significant linear relationships between some AHFRs (e.g., HBB and PBEB), suggesting their similar commercial applications and sources in the environment. The estimated daily intakes of AHFRs through consumption of green mussels by the local population in South China were 0.05-0.14 ng/kg body weight/day and 0.17-0.44 ng/kg body weight/day based on the mean and 95th concentrations, respectively. To the best of our knowledge, the present study is the first to report AHFRs and dehalogenated products in green mussels.


Observations on the influenza epidemic of November/December 1989.
This paper reports on the surveillance of influenza by the weekly returns service of the Royal College of General Practitioners during the epidemic of November/December 1989. An epidemic of influenza became evident in mid-November and incidence peaked in the week beginning 6 December. The increase in incidence of influenza-like illness and of aggregated data for all respiratory disease to above the levels for non-epidemic years occurred one week before that attributed to influenza. The pattern of incidence was similar in the three geographic regions of England and Wales. The peak was first achieved in the age group 5-14 years and last in age 65+ years. The pattern of deaths from all causes closely followed the pattern of respiratory disease with an interval of between one and two weeks. During the period 15 November to the end of the year there were approximately twice as many people reporting respiratory disease than was usual for this time of year. The peak weekly incidence was the highest recorded for 12 years but it was substantially less than the peaks for the winters of 1969/70, 1972/73 and 1975/76. Further research is in progress to establish the most effective means of monitoring influenza epidemics.


Ovarian cycling and reproductive state shape the vaginal microbiota in wild baboons.
The vaginal microbiome is an important site of bacterial-mammalian symbiosis. This symbiosis is currently best characterized for humans, where lactobacilli dominate the microbial community and may help defend women against infectious disease. However, lactobacilli do not dominate the vaginal microbiota of any other mammal studied to date, raising key questions about the forces that shape the vaginal microbiome in non-human mammals. We used Illumina sequencing of the bacterial 16S rRNA gene to investigate variation in the taxonomic composition of the vaginal microbiota in 48 baboons (Papio cynocephalus), members of a well-studied wild population in Kenya. Similar to prior studies, we found that the baboon vaginal microbiota was not dominated by lactobacilli. Despite this difference, and similar to humans, reproductive state was the dominant predictor of baboon vaginal microbiota, with pregnancy, postpartum amenorrhea, and ovarian cycling explaining 18% of the variance in community composition. Furthermore, among cycling females, a striking 39% of variance in community composition was explained by ovarian cycle phase, with an especially distinctive microbial community around ovulation. Periovulatory females exhibited the highest relative abundance of lactic acid-producing bacteria compared to any other phase, with a mean relative abundance of 44%. To a lesser extent, sexual behavior, especially a history of shared sexual partners, also predicted vaginal microbial similarity between baboons. Despite striking differences in their dominant microbes, both human and baboon vaginal microbiota exhibit profound changes in composition in response to reproductive state, ovarian cycle phase, and sexual behavior. We found major shifts in composition during ovulation, which may have implications for disease risk and conception success. These findings highlight the need for future studies to account for fine-scale differences in reproductive state, particularly differences between the various phases of the ovarian cycle. Overall, our work contributes to an emerging understanding of the forces that explain intra- and inter-individual variation in the mammalian vaginal microbiome, with particular emphasis on its role in host health and disease risk.


Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.
Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population. Forty-five compounds, including twenty-eight drugs approved for use in humans, were evaluated against XMRV replication in vitro. We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively. Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication. When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses. If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials.


The Chloroplast SRP Systems of Chaetosphaeridium globosum and Physcomitrella patens as Intermediates in the Evolution of SRP-Dependent Protein Transport in Higher Plants.
The bacterial signal recognition particle (SRP) mediates the cotranslational targeting of membrane proteins and is a high affinity complex consisting of a SRP54 protein subunit (Ffh) and an SRP RNA. The chloroplast SRP (cpSRP) pathway has adapted throughout evolution to enable the posttranslational targeting of the light harvesting chlorophyll a/b binding proteins (LHCPs) to the thylakoid membrane. In spermatophytes (seed plants), the cpSRP lacks the SRP RNA and is instead formed by a high affinity interaction of the conserved 54-kD subunit (cpSRP54) with the chloroplast-specific cpSRP43 protein. This heterodimeric cpSRP recognizes LHCP and delivers it to the thylakoid membrane. However, in contrast to spermatophytes, plastid SRP RNAs were identified within all streptophyte lineages and in all chlorophyte branches. Furthermore, it was shown that cpSRP43 does not interact with cpSRP54 in chlorophytes (e.g., Chlamydomonas reinhardtii). In this study, we biochemically characterized the cpSRP system of the charophyte Chaetosphaeridium globosum and the bryophyte Physcomitrella patens. Interaction studies demonstrate low affinity binding of cpSRP54 to cpSRP43 (Kd ~10 μM) in Chaetosphaeridium globosum and Physcomitrella patens as well as relatively low affinity binding of cpSRP54 to cpSRP RNA (Kd ~1 μM) in Physcomitrella patens. CpSRP54/cpSRP43 complex formation in charophytes is supported by the finding that specific alterations in the second chromodomain of cpSRP43, that are conserved within charophytes and absent in land plants, do not interfere with cpSRP54 binding. Furthermore, our data show that the elongated apical loop structure of the Physcomitrella patens cpSRP RNA contributes to the low binding affinity between cpSRP54 and the cpSRP RNA.


Crossed hands strengthen and diversify proprioceptive drift in the self-touch illusion.
In the self-touch illusion (STI), some can feel that both hands are touching each other even when they are separated actually. This is achieved by giving synchronized touches to both hands. Because the STI involves both hands (an administrating hand and a receptive hand) of a single person, two types of proprioceptive drifts (PDs) simultaneously occur in such a way that both hands are attracted to each other. It is known that the PD distance is generally larger for the administrating hand than for the receptive hand when the two hands are uncrossed. However, it remains unclear why such an asymmetrical relationship is observed universally. In this study, we conducted two types of experiment to induce the STI. The first experiment involved four conditions combining a factor of "whether the hands are uncrossed or crossed" and a factor of "whether the administrating hand is resting or active on the surface," with the receptive (left) hand located at the body's midline. The result demonstrated that crossing hands and resting on surface (ROS) induced the STI. Specifically, crossing hands enhanced the amount of PD distance by more than two or three times. Moreover, it is interesting that strong PD with dominance of the receptive hand, which did not appear in the uncrossed condition, was observed frequently. The second experiment collected seven "illusion-sensitive" participants from the first experiment, all of whom had a strong tendency to feel the self-touch, and examined the effect of the location of the body midline on the PD when hands are crossed with the administrating hand ROS. The result demonstrated that the dominant hand on the PD completely differed among participants, but was relatively stable over the midline position and time in the same person. We also found that a small number of participants exhibited quite a different pattern of the PD in the identical posture. On the basis of the results, we analyze in detail how the dominant hand on the PD is determined in the STI.


Scottish healthcare student's perceptions of an interprofessional ward simulation: An exploratory, descriptive study.
The most memorable learning occurs during placement. Simulated interprofessional learning is a logical learning opportunity to help healthcare professionals work beyond their professional silos. In this qualitative study, we investigated the perceived learning of students from six health professions (adult nursing, diagnostic radiography, occupational therapy, physiotherapy, dietetics, and pharmacy) from their participation in a 45 min interprofessional ward simulation. Semistructured focus groups were undertaken, and data were analyzed using framework analysis. Two overarching themes were evident, each of which had subthemes: (i) the ward simulation as an interprofessional education opportunity (subthemes: reality of situations and interactions); and (ii) the perceived learning achieved (subthemes: professional roles, priorities, respect, communication, teamwork, and quality of care). The results indicated that a short interprofessional ward simulation, unsupported by additional learning opportunities or directed study, is a useful and engaging interprofessional learning opportunity. Students appear to have learnt important key messages central to the interprofessional education curricula to help develop practitioners who can effectively work together as an interprofessional team, and that this learning is partly due to simulation allowing things to go wrong.


Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis.
We used pharmacological and surgical methods to determine the contribution of several neural components to joint injury in rats with adjuvant-induced arthritis. Both neonatal administration of capsaicin, which eliminates small-diameter afferents, and peripheral sympathectomy, which depletes catecholamines, attenuated joint injury. In contrast, the arthritis was more severe in spontaneously hypertensive rats, which have increased sympathetic tone. To address the contribution of the central vs peripheral afferent terminal selectively, a group of rats underwent unilateral dorsal rhizotomy. These rats developed a more severe arthritis in the deafferented limb. The increase in arthritis severity produced by dorsal rhizotomy could be reduced by prior sympathectomy or, less effectively, by prior treatment with capsaicin. The latter observation suggests that large-diameter afferents that are cut during dorsal rhizotomy also influence inflammation. Finally, intracerebroventricular injection of morphine attenuated the severity of arthritis, possibly through activation of bulbospinal sympathoinhibitory circuits. Taken together, these data indicate that no one class of nerve fiber is wholly responsible for the neurogenic component of inflammation in experimental arthritis but that large- and small-diameter afferents, sympathetic efferents, and CNS circuits that modulate those fiber systems all influence the severity of joint injury in arthritic rats.


Heart rate, startle response, and intrusive trauma memories.
The current study adopted the trauma film paradigm to examine potential moderators affecting heart rate (HR) as an indicator of peritraumatic psychological states and as a predictor of intrusive memories. We replicated previous findings that perifilm HR decreases predicted the development of intrusive images and further showed this effect to be specific to images rather than thoughts, and to detail rather than gist recognition memory. Moreover, a group of individuals showing both an atypical sudden reduction in HR after a startle stimulus and higher trait dissociation was identified. Only among these individuals was lower perifilm HR found to indicate higher state dissociation, fear, and anxiety, along with reduced vividness of intrusions. The current findings emphasize how peritraumatic physiological responses relate to emotional reactions and intrusive memory. The moderating role of individual difference in stress defense style was highlighted.


Effect of Application Method and Rate on Residual Efficacy of Mefenoxam and Phosphorous Acid Fungicides in the Control of Pink Rot of Potato.
Experiments were conducted to examine the effectiveness of rate and method of phosphorous acid application for controlling pink rot of potato (Solanum tuberosum) caused by Phytophthora erythroseptica. Replicated small-plot and replicated split commercial field trials were established in commercial production fields in Minnesota from 2006 to 2009. Fungicides were applied in-furrow at planting, or as one, two, or three foliar applications via ground sprayer, irrigation system (chemigation), or fixed-wing aircraft. Phosphorous acid efficacy was compared to mefenoxam, the fungicide commonly utilized to manage pink rot, either by determining natural infections in the field or by inoculating eyes of harvested tubers using a mefenoxam-sensitive and -resistant isolate of P. erythroseptica via postharvest challenge inoculation. In replicated small plot trials, both in-furrow and two foliar applications of mefenoxam controlled tuber rot in the field, and significantly controlled tuber rot in storage. Phosphorous acid also reduced tuber rot in the field when applied two or three times to the foliage. Although phosphorous acid was ineffective when applied in-furrow, one, two, and three foliar applications and a postharvest application of phosphorous acid controlled mefenoxam-sensitive and -resistant isolates of P. erythroseptica during storage for 187 days, while mefenoxam failed to control the resistant isolate. In replicated split commercial field trials, two aerial applications of phosphorous acid were as effective as three applications in reducing pink rot incidence in tubers inoculated postharvest. Three aerial applications were as effective as three chemigation applications in replicated split commercial field trials in 2008, but provided significantly greater protection than chemigation in 2009.


Linear growth and final height in patients with systemic juvenile idiopathic arthritis treated with longterm glucocorticoids.
To assess linear growth and final height in patients given glucocorticoids during childhood for systemic juvenile idiopathic arthritis (JIA). Heights throughout followup for JIA and final height were recorded in 24 patients. Height data were expressed as the height standard deviation score for chronological age (HSDS/CA). Final height was compared to reference values for the French population and to target height. During glucocorticoid therapy, mean loss of HSDS/CA was -2.7 +/- 1.5 and was positively correlated with prednisone therapy duration (p < 0.01). After prednisone discontinuation, 17 patients (70%) had catch-up growth and 7 (30%) continued to experience slow linear growth. Mean final height was -2.0 +/- 1.8 HSDS and was correlated with mean height at prednisone discontinuation (p < 0.0001). Mean final height was significantly greater in the patients with catch-up growth at prednisone discontinuation (-1.5 +/- 1.6 vs -3.6 +/- 1.2 HSDS), and 87% of patients had a final height below their target height. These data suggest that chronic inflammation and prednisone therapy may adversely affect growth in patients with JIA, and that final height may be closely dependent both on the severity of growth retardation during the active phase of the disease and on linear growth after remission. Thus treatments like growth hormone presently under investigation to improve final height may be most effective when given early after disease onset and/or at remission.


Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects.
Low plasma fibrinolytic activity in association with increased plasma plasminogen activator inhibitor 1 (PAI-1) levels has been linked to an increased risk of atherosclerosis in obesity and type 2 diabetes. We tested the hypothesis that troglitazone, which improves insulin sensitivity and lowers plasma insulin levels in insulin-resistant obese subjects and patients with type 2 diabetes, would also lower circulating PAI-1 antigen concentrations and activity. We assessed insulin sensitivity (5-h, 80 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) and measured plasma PAI-1 antigen and activities and tissue plasminogen activator (tPA) in 14 patients with type 2 diabetes and 20 normal control subjects (10 lean, 10 obese) before and after 3 months of treatment with troglitazone (600 mg/day). At baseline, plasma PAI-1 antigen levels after an overnight fast were significantly higher in the obese (33.5 +/- 4.7 microg/l) and type 2 diabetic subjects (54.9 +/- 6.3 microg/l) than in the lean control subjects (16.3 +/- 3.2 microg/l; P < 0.01 and P < 0.001, respectively). Troglitazone decreased plasma PAI-1 antigen concentrations in the diabetic patients (36.8 +/- 5.0 microg/l; P < 0.001 vs. baseline), but the reduction in the obese subjects did not reach statistical significance (baseline, 33.5 +/- 4.7; after troglitazone, 25.6 +/- 5.2 microg/l). Changes in plasma PAI-1 activity paralleled those of PAI-1 antigen. The extent of the reduction in plasma PAI-1 antigen concentrations in the diabetic patients after troglitazone correlated with the reductions in fasting plasma insulin (r = 0.60, P < 0.05), nonesterified fatty acid (r = 0.63, P < 0.02), and glucose concentrations (r = 0.64, P < 0.02) but not with the improvement in glucose disposal rates during the glucose clamps. Three nonresponders to troglitazone with respect to effects on insulin sensitivity and fasting glucose and insulin levels also had no reduction in circulating PAI-1. In conclusion, troglitazone enhances fibrinolytic system activity in insulin-resistant type 2 diabetic patients. This effect appears to be intimately linked to its potential to lower plasma insulin levels and improve glycemic control through its peripheral tissue insulin-sensitizing effects.


Onchocerciasis in pre-primary school children in Nigeria: lessons for onchocerciasis country control programme.
There is limited data on the prevalence of onchocerciasis in young children in Nigeria, partly because treatment with the effective drug Ivermectin has been contra-indicated in children less than 5. As the risk of complications of onchocerciasis is related to duration and intensity of infection, it would be beneficial to know the prevalence in young children for design of control programmes. A study was therefore undertaken to determine the prevalence of onchocerciasis in 642 children 0-4 years old in a rain forest endemic community in South East Nigeria. The overall onchocerciasis prevalence (positive skin snips) for children 0-4 years old in three Local Government Areas in Enugu State, Eastern Nigeria was 15.7% with no significant difference in infection rates between male and female children. There was no detectable infection in children less than 1 year old. Characteristic onchocercal rash was identified in 11.1% of the children and presence of typical onchocercal subcutaneous palpable nodules in 4.6%. Total prevalence for adults in the same population was found to be 26.9%. This indicates that in onchocerciasis endemic communities, everybody may be at risk of infection irrespective of age.


Solar energy harvesting in the epicuticle of the oriental hornet (Vespa orientalis).
The Oriental hornet worker correlates its digging activity with solar insolation. Solar radiation passes through the epicuticle, which exhibits a grating-like structure, and continues to pass through layers of the exo-endocuticle until it is absorbed by the pigment melanin in the brown-colored cuticle or xanthopterin in the yellow-colored cuticle. The correlation between digging activity and the ability of the cuticle to absorb part of the solar radiation implies that the Oriental hornet may harvest parts of the solar radiation. In this study, we explore this intriguing possibility by analyzing the biophysical properties of the cuticle. We use rigorous coupled wave analysis simulations to show that the cuticle surfaces are structured to reduced reflectance and act as diffraction gratings to trap light and increase the amount absorbed in the cuticle. A dye-sensitized solar cell (DSSC) was constructed in order to show the ability of xanthopterin to serve as a light-harvesting molecule.


Neural bases for addictive properties of benzodiazepines.
Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha1-containing GABA(A) receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of alpha1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction liability.


Detecting Potential Underreporting of Suicide Ideation Among U.S. Military Personnel.
Using a military sample comprised largely of National Guard personnel, zero-inflation negative binomial regression was applied to estimate the effects of indirect, nonface valid indicators of suicide ideation [Thwarted Belongingness (TB), Perceived Burdensomeness (PB), and Hopelessness], in predicting suicide ideation. Data from a sample of 497 military personnel (82.1% male; mage = 27.24; range = 18-59) were analyzed. TB and the interaction of TB with Hopelessness were significant predictors in the logistic regression, and in the negative binomial regression, the main effects of TB and hopelessness, and the interactions of TB with hopelessness and PB with hopelessness were significant. The findings further indicated that approximately 10% of those not reporting ideation would be predicted to be ideators. Clinically, these results indicate that, in samples reluctant to report ideation, the assessment of suicide risk may improve through the use of relevant measures that do not explicitly reference suicide thoughts.


Deciphering Biosignatures in Planetary Contexts.
Microbial life permeates Earth's critical zone and has likely inhabited nearly all our planet's surface and near subsurface since before the beginning of the sedimentary rock record. Given the vast time that Earth has been teeming with life, do astrobiologists truly understand what geological features untouched by biological processes would look like? In the search for extraterrestrial life in the Universe, it is critical to determine what constitutes a biosignature across multiple scales, and how this compares with "abiosignatures" formed by nonliving processes. Developing standards for abiotic and biotic characteristics would provide quantitative metrics for comparison across different data types and observational time frames. The evidence for life detection falls into three categories of biosignatures: (1) substances, such as elemental abundances, isotopes, molecules, allotropes, enantiomers, minerals, and their associated properties; (2) objects that are physical features such as mats, fossils including trace-fossils and microbialites (stromatolites), and concretions; and (3) patterns, such as physical three-dimensional or conceptual n-dimensional relationships of physical or chemical phenomena, including patterns of intermolecular abundances of organic homologues, and patterns of stable isotopic abundances between and within compounds. Five key challenges that warrant future exploration by the astrobiology community include the following: (1) examining phenomena at the "right" spatial scales because biosignatures may elude us if not examined with the appropriate instrumentation or modeling approach at that specific scale; (2) identifying the precise context across multiple spatial and temporal scales to understand how tangible biosignatures may or may not be preserved; (3) increasing capability to mine big data sets to reveal relationships, for example, how Earth's mineral diversity may have evolved in conjunction with life; (4) leveraging cyberinfrastructure for data management of biosignature types, characteristics, and classifications; and (5) using three-dimensional to n-D representations of biotic and abiotic models overlain on multiple overlapping spatial and temporal relationships to provide new insights.


Chemical and microbiological evaluation of novel chemical treatment methods for acid sulfate soils.
Naturally occurring sulfide rich deposits are common along the northern Baltic Sea coast that when exposed to air, release large amounts of acid and metals into receiving water bodies. This causes severe environmental implications for agriculture, forestry, and building of infrastructure. In this study, we investigated the efficiency of ultrafine-grained calcium carbonate and peat (both separately and in combination) to mitigate acid and metal release. The experiments were carried out aerobically that mimicked summer conditions when the groundwater level is low and acid sulfate soils are exposed to oxygen, and anaerobically that is similar to autumn to spring conditions. The ultrafine-grained calcium carbonate dissipated well in the soil and its effect alone and when mixed with peat raised the pH and reduced pyrite dissolution while peat alone was similar to the controls and did not halt metal and acid release. High throughput 16S rRNA gene sequencing identified populations most similar to characterized acidophiles in the control and peat treated incubations while the acidophilic like populations were altered in the calcium carbonate alone and calcium carbonate plus peat treated acid sulfate soils. Coupled with the geochemistry data, it was suggested that the acidophiles were inactivated by the high pH in the presence of calcium carbonate but catalyzed pyrite dissolution in the controls and peat incubations. In conclusion, the anaerobic conditions during winter would likely be sufficient to mitigate acid production and metal release from acid sulfate soils and in the summer, treatment with calcium carbonate was the best mitigation method.


Effect of crude fiber and total dietary fiber on the calculated nitrogen-free extract and metabolizable energy content of various dog foods fed to client-owned dogs with osteoarthritis.
To compare measurements of crude fiber (CF) and total dietary fiber (TDF) for various dog foods and their effect on the calculated nitrogen-free extract and metabolizable energy (ME) content, and to compare label-guaranteed and laboratory-analyzed macronutrient values. 51 dog foods fed to client-owned dogs with osteoarthritis. Foods were analyzed for dry matter, ash, crude protein, acid-hydrolyzed fat, CF, and TDF. Metabolizable energy was calculated by use of a formula with modified Atwater factors and formulas recommended by the National Research Council that included both CF and TDF values. Linear regression analysis was performed to determine the correlation between CF and TDF values. Only a few foods failed to conform to the guaranteed analysis for all macronutrients except for CF, in which approximately 40% of the foods exceeded the guaranteed maximum values. The CF and TDF values were moderately correlated (r = 0.843). Correlations among CF- and TDF-based ME estimations were moderate with use of the modified Atwater formula and strong with use of the National Research Council formulas (r = 0.86 and r = 0.91, respectively). Values for CF were the most variable of the macronutrients of the evaluated dog foods and results suggested that CF is an incomplete and inaccurate measurement of dietary fiber content and, thus, its inaccuracy may lead to inaccurate and variable ME values.


Diagnostic and management strategies for lateral pelvic lymph nodes in low rectal cancer-a review of the evidence.
Patients with low rectal cancer who have enlarged lateral pelvic lymph nodes are known to have a worse prognosis. There is however uncertainty over what constitutes a lateral pelvic lymph node of clinical significance. As the main modality for the detection of such lymph nodes is magnetic resonance imaging (MRI), characteristics of these lateral lymph nodes identified may have prognostic value and assist with guiding treatment. Options to manage such lateral lymph nodes includes neoadjuvant chemoradiotherapy as well as lateral lymph node dissection. Surgery is extensive and may lead to significant morbidity to the patient. This review article evaluates diagnostic and management strategies in patients with lateral pelvic lymph nodes in low rectal cancer.


Staying hepatitis C negative: A systematic review and meta-analysis of cure and reinfection in people who inject drugs.
Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in people who inject drugs (PWID). A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.


The societal costs of problem gambling in Sweden.
Problem gambling is a public health issue affecting both the gamblers, their families, their employers, and society as a whole. Recent law changes in Sweden oblige local and regional health authorities to invest more in prevention and treatment of problem gambling. The economic consequences of gambling, and thereby the potential economic consequences of policy changes in the area, are unknown, as the cost of problem gambling to society has remained largely unexplored in Sweden and similar settings. A prevalence-based cost-of-illness study for Sweden for the year 2018 was conducted. A societal approach was chosen in order to include direct costs (such as health care and legal costs), indirect costs (such as lost productivity due to unemployment), and intangible costs (such as reduced quality of life due to emotional distress). Costs were estimated by combining epidemiological and unit cost data. The societal costs of problem gambling amounted to 1.42 billion euros in 2018, corresponding to 0.30% of the gross domestic product. Direct costs accounted only for 13% of the total costs. Indirect costs accounted for more than half (59%) of the total costs, while intangible costs accounted for 28%. The societal costs were more than twice as high as the tax revenue from gambling in 2018. Direct and indirect costs of problem gambling combined amounted to one third of the equivalent costs of smoking and one sixth of the costs of alcohol consumption in Sweden. Problem gambling is increasingly recognized as a public health issue. The societal costs of it are not negligible, also in relation to major public health issues of an addictive nature such as smoking and alcohol consumption. Direct costs for prevention and treatment are very low. A stronger focus on prevention and treatment might help to reduce many of the very high indirect and intangible costs in the future.


Rivaroxaban-induced chest wall spontaneous expanding hematoma.
Rivaroxaban is an oral direct Factor Xa inhibitor approved in the European Union and the United Sates for the single-drug treatment of several thromboembolic diseases in adults. Ιt has been evaluated in large phase III clinical trials and has been found to have similar efficacy and safety with standard therapy. Herein, is described a very rare case of a rivaroxaban-induced spontaneous expanding chest wall hematoma, that required surgical intervention, in a breast cancer patient. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of hematoma and treatment with rivaroxaban. Physicians should be cautious when prescribing rivaroxaban in groups of patients associated with increased bleeding risk such as patients with impaired renal or hepatic function, hypertension, coronary heart disease, heart failure, patients with certain types of cancers and patients receiving concomitant medications which may alter the pharmacokinetic or pharmacodymamic parameters of rivaroxaban. Anticoagulant treatment should be tailored to each individual patient weighing the bleeding risk against the risk of recurrent thrombosis.


Agonist-mediated endocytosis of rat somatostatin receptor subtype 3 involves beta-arrestin and clathrin coated vesicles.
Agonist-induced endocytosis of somatostatin receptors determines subsequent cellular responsiveness to peptide agonist and influences somatostatin receptor scintigraphy, a technique to image various tumours. We examined the internalization of sst3HSV, an epitope-tagged type 3 somatostatin receptor, in transfected rat neuroendocrine insulinoma cells. Stimulation of these cells with somatostatin induced trafficking of coexpressed enhanced green fluorescence protein/beta-arrestin1 fusion protein and sst3HSV to colocalize in the same endocytic vesicles. Coexpression of a dominant negative mutant of the arrestin fusion protein with the receptor blocked the internalization of sst3HSV. Stimulation with somatostatin also induced the transient translocation of alpha-adaptin, a component of the adaptor protein complex 2, to the plasma membrane. alpha-adaptin and clathrin colocalized with the receptor. By electron microscopy, we observed internalized sst3 in clathrin coated pits, endosomes and at the limiting membrane of multivesicular bodies, a location typical for receptors being recycled. Concordantly, we observed sst3HSV colocalized with Rab11 in a perinuclear compartment which is likely to correspond to the pericentriolar recycling endosome. Thus, agonist-induced endocytosis of sst3 depends on its interaction with beta-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment.


Tuning the cavity modes of a Fabry-Perot resonator using gold nanoparticles.
We study the interaction between a planar Fabry-Perot microcavity and a single embedded gold nanoparticle. We record spatially resolved white-light transmission spectra and show that the interaction between microcavity and nanoparticle gives rise to a redshift of the cavity modes, in accordance with the Bethe-Schwinger cavity perturbation formula. The spectral tuning of cavity modes by discrete nanoparticles can be exploited for applications such as optical and micromechanical sensing.


Magnetic resonance imaging analysis of cardiac cycle events in diabetic rats: the effect of angiotensin-converting enzyme inhibition.
Non-invasive magnetic resonance imaging (MRI) was used to characterize changes in left and right ventricular cardiac cycles following induction of experimental, streptozotocin (STZ)-induced, diabetes in male Wistar rats at different ages. The effects of the angiotensin-converting enzyme (ACE) inhibitor captopril upon such chronic physiological changes were then evaluated, also for the first time. Diabetes was induced at the age of 7 weeks in two experimental groups, of which one group was subsequently maintained on captopril (2 g l(-1))-containing drinking water, and at 10 and 13 weeks in two further groups. The fifth group provided age-matched controls. All groups (each n = 4 animals) were scanned consistently at 16 weeks, in parallel with timings used in earlier studies that employed this experimental model. Cine magnetic resonance (MR) image acquisition provided transverse sections through both ventricles at twelve time points covering systole and most of diastole. These yielded reconstructions of cardiac anatomy used to derive critical functional indices and their dependence upon time following the triggering electrocardiographic R waves. The left and right ventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes (SV), and ejection fractions (EF) calculated from each, control and experimental, group showed matching values. This confirmed a necessary condition requiring balanced right and left ventricular outputs and further suggested that STZ-induced diabetes produced physiological changes in both ventricles. Absolute left and right ventricular SVs were significantly altered in all diabetic animals; EDVs and EFs significantly altered in animals diabetic from 7 and 10 but not 13 weeks. When normalized to body weight, left and right ventricular SVs had significantly altered in animals diabetic from 7 and 10 weeks but not 13 weeks. Normalized left ventricular EDVs were also significantly altered in animals diabetic from 7 and 10 weeks. However, normalized right ventricular EDVs were significantly altered only in animals made diabetic from 7 weeks. Diabetic hearts showed major kinetic changes in left and right ventricular contraction (ejection) and relaxation (filling). Both the initial rates of volume change (dV/dt) in both ventricles and the plots of dV/dt values through the cardiac cycle demonstrated more gradual developments of tension during systole and relaxation during diastole. Estimates of the derived left ventricular performance parameters of cardiac output, cardiac power output and stroke work in control animals were comparable with human values when normalized to both body (or cardiac) weight and heart rate. All deteriorated with diabetes. Comparisons of experimental groups diabetic from 7 weeks demonstrated that captopril treatment relieved the alterations in critical volumes, dependence of SV upon EDV, kinetics of systolic contraction and diastolic relaxation and in the derived indicators of ventricular performance. This study represents the first demonstration using non-invasive MRI of early, chronic changes in diastolic filling and systolic ejection in both the left and the right ventricles and of their amelioration by ACE inhibition following STZ-induction of diabetes in intact experimental animals.


The specificity of expertise: for whom is the clave pattern the "key" to salsa music?
Each Latin salsa music style is associated with a characteristic clave pattern that constitutes an essential structure for performers. In this article we asked what types of expertise are needed to detect the correct salsa-clave pairing. Using two clave patterns (the 3-2 and 2-3 son clave) and three manipulated alternatives, we asked listeners to choose the correct clave pattern for a variety of bomba, calypso, mambo and merengue excerpts. The results of Studies 1 and 2 show that listeners unfamiliar with salsa were unable to detect the correct salsa-clave pairing. Listeners who had some music training or were familiar with salsa detected the need for syncopation but not the specific pairing. Only musicians well-acquainted with salsa correctly detected the salsa-clave pairing. Studies 3 and 4 showed that incorrect choices were not due to an inability to distinguish between the alternatives: both adults and five-year-olds could easily tell apart the various patterns we used. We conclude that the distinction between the 2-3 and 3-2 claves is not inherent in the music itself, but rather is a convention to be learned through exposure and training. We discuss the results using an analogy to language learning.


Selective loading and processing of prespacers for precise CRISPR adaptation.
CRISPR-Cas immunity protects prokaryotes against invading genetic elements1. It uses the highly conserved Cas1-Cas2 complex to establish inheritable memory (spacers)2-5. How Cas1-Cas2 acquires spacers from foreign DNA fragments (prespacers) and integrates them into the CRISPR locus in the correct orientation is unclear6,7. Here, using the high spatiotemporal resolution of single-molecule fluorescence, we show that Cas1-Cas2 selects precursors of prespacers from DNA in various forms-including single-stranded DNA and partial duplexes-in a manner that depends on both the length of the DNA strand and the presence of a protospacer adjacent motif (PAM) sequence. We also identify DnaQ exonucleases as enzymes that process the Cas1-Cas2-loaded prespacer precursors into mature prespacers of a suitable size for integration. Cas1-Cas2 protects the PAM sequence from maturation, which results in the production of asymmetrically trimmed prespacers and the subsequent integration of spacers in the correct orientation. Our results demonstrate the kinetic coordination of prespacer precursor selection and PAM trimming, providing insight into the mechanisms that underlie the integration of functional spacers in the CRISPR loci.


It goes both ways: a cross-sectional study of buying and selling sex among young behaviourally bisexual men in Vientiane, Laos.
Background Transactional sex may increase risk of HIV and sexually transmissible infections (STIs). In Laos, men who have sex with men are disproportionately affected by HIV, and bisexual behaviour among men is relatively common. The occurrence of transactional sex among behaviourally bisexual men in Vientiane, Laos was explored. In 2010, behaviourally bisexual men were recruited through enhanced snowball sampling to complete a behavioural survey. Reports of transactional sex partners (anal/vaginal sex) in the previous year, by direction of payment and partner gender, is described. Of 88 participating behaviourally bisexual men (median age 22 years), 17 (19%) reported only selling sex, eight (9%) reported only paying for sex and nine (10%) reported both selling and paying for sex. Men reporting any transactional sex reported a median of four transactional sex partners and reported a higher number of total sex partners in the previous 12 months (median: 18.5 partners) than men reporting no transactional sex partners (median: 6 partners). Of 26 men who reported selling sex, 15 (58%) were paid by females, 15 (58%) were paid by males and 14 (55%) were paid by transgender sex partner(s); 11 (42%) reported consistent condom use (CCU) when selling sex. Of 17 men who reported paying for sex, 13 (76%) paid females, six (35%) paid males and two (12%) paid transgender partner(s); eight (47%) reported CCU when paying for sex. Young behaviourally bisexual men engaging in transactional sex may be at increased risk of HIV and STIs. Prevention interventions should consider the transient and informal nature of transactional sex in this population.


Inbreeding depression under drought stress in the rare endemic Echium wildpretii (Boraginaceae) on Tenerife, Canary islands.
How climate-change induced environmental stress may alter the effects of inbreeding in patchy populations of rare species is poorly understood. We investigated the fitness of progeny from experimental self- and cross-pollinations in eight populations of different size of Echium wildpretii, a rare endemic plant of the arid subalpine zone of the Canarian island of Tenerife. As control treatments we used open pollination and autonomous selfing. The seed set of open-pollinated flowers was 55% higher than that of autonomously selfed flowers, showing the importance of animal pollination for reproductive success. The seed set, seed mass and germination rate of seedlings of hand-selfed flowers was similar to that of hand-crossed flowers, indicating weak inbreeding depression (seed set -4.4%, seed mass -4.1%, germination -7.3%). Similarly, under normal watering there were no significant effects of inbreeding on seedling survival (-3.0%). However, under low watering of seedlings inbreeding depression was high (survival -50.2%). Seed set of open- and hand-outcrossed-pollinated flowers was higher in large than in small populations, possibly due to more frequent biparental inbreeding in the latter. However, later measures of progeny fitness were not significantly influenced by population size. We predict that increasing drought duration and frequency due to climate change and reductions of population sizes may increase inbreeding depression in this charismatic plant species and thus threaten its future survival in the longer term.


Bovine glycogenosis type II. Biochemical and morphological characteristics of skeletal muscle in culture.
The biochemical and morphological properties of cultured skeletal muscle from calves born into a herd of cattle, which are heterozygous for glycogenosis type II, were studied over 17 days. Muscle was cultured by a modification of the explant technique in which the mononucleated cells that grew from the explants were subcultured. Skeletal muscle from animals up to 15 months of age grew in culture to produce mature, cross-striated and spontaneously contractile myotubes. The creatine kinase activity was 310 (+/- 45.4) mU/mg protein on day 7 when fusion was complete, and 210 (+/- 15.1) mU/mg protein on day 17 of culture. Mature muscle cultures from animals affected by glycogenosis type II showed the characteristic biochemical and morphological abnormalities previously observed in vivo. Acid alpha-glucosidase activity was absent whereas the activities of neutral alpha-glucosidase, lysosomal alpha-mannosidase and creatine kinase were the same as in cultures of unaffected muscle. The concentration of glycogen was higher in cultured affected muscle than in cultured unaffected muscle. On days 7, 9 and 17 of culture the glycogen concentrations were 66.7 (+/- 2.7), 89.0 (+/- 5.5) and 120.3 (+/- 34.2) micrograms/mg protein respectively in affected muscle and 51.8 (+/- 3.6), 59.9 (+/- 5.4) and 55.4 (+/- 1.0) micrograms/mg protein respectively in non-affected muscle. Electron microscopic studies showed that the glycogen accumulated within the lysosomes. These results indicate that bovine glycogenosis type II is expressed in tissue culture since the cultured skeletal muscle from affected animals shows the same abnormalities as skeletal muscle in vivo.


Regulation of apical growth and hyphal branching in Streptomyces.
The filamentous bacteria Streptomyces grow by tip extension and through the initiation of new branches, and this apical growth is directed by a polarisome-like complex involving the essential polarity protein DivIVA. New branch sites must be marked de novo and, until recently, there was no understanding of how these new sites are selected. Equally, hyphal branching patterns are affected by environmental conditions, but there was no insight into how polar growth and hyphal branching might be regulated in response to external or internal cues. This review focuses on recent discoveries that reveal the principal mechanism of branch site selection in Streptomyces, and the first mechanism to be identified that regulates polarisome behaviour to modulate polar growth and hyphal branching.


[Case report of anti-NMDA receptor encephalitis suspected of schizophrenia].
Recently, paraneoplastic encephalitis associated with ovarian teratoma, which predomi nantly affects young women, has been reported. Its symptoms are severe but often treatment-responsive and reversible. Various psychiatric symptoms occurring shortly after onset are characteristic of this encephalitis. A 22-year-old female who had a fever and common cold-like symptoms presented with short-term memory loss. She was suspected to have viral encephalitis, but the cerebrospinal fluid (CSF) showed no marked change. Shortly after that, she developed delusions and hallucinations and presented with psychomotor excitement. She was suspected of having schizophrenia and admitted to the psychiatry department. However, several days after admission, she showed upper limb convulsion, orofacial dyskinesias, and central hypoventilation and became unresponsive. The results of laboratory tests were within the normal range, and there was no marked elevation of anti-viral antibody titers. Brain imaging was normal, but a solid tumor containing soft tissue and calcified components, probably an ovarian teratoma, was discovered on an abdominal CT scan. Anti-N-methyl-D-aspartate (NMDA) receptor antibody was positive in her CSF and blood serum, and we diagnosed her with "Anti-NMDA receptor encephalitis". Gamma globulin was very effective, and the ovarian teratoma was removed. Finally, she could be discharged from our hospital without any sequela, and returned to her job. Psychiatrists often encounter encephalitis patients with psychiatric symptoms. If the type of encephalitis is unknown, we should keep this disease in mind.


WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.
The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.


Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis.
Although recent reports suggest that the endoplasmic reticulum (ER) stress response is induced in association with the development of inflammatory bowel disease, its role in the pathogenesis of inflammatory bowel disease remains unclear. The CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a transcription factor that is involved in the ER stress response, especially ER stress-induced apoptosis. In this study, we found that experimental colitis was ameliorated in CHOP-null mice, suggesting that CHOP exacerbates the development of colitis. The mRNA expression of Mac-1 (CD11b, a positive regulator of macrophage infiltration), Ero-1alpha, and Caspase-11 (a positive regulator of interleukin-1beta production) in the intestine was induced with the development of colitis, and this induction was suppressed in CHOP-null mice. ERO-1alpha is involved in the production of reactive oxygen species (ROS); an increase in ROS production, which is associated with the development of colitis in the intestine, was suppressed in CHOP-null mice. A greater number of apoptotic cells in the intestinal mucosa of wild-type mice were observed to accompany the development of colitis compared with CHOP-null mice, suggesting that up-regulation of CHOP expression exacerbates the development of colitis. Furthermore, this CHOP activity appears to involve various stimulatory mechanisms, such as macrophage infiltration via the induction of Mac-1, ROS production via the induction of ERO-1alpha, interleukin-1beta production via the induction of Caspase-11, and intestinal mucosal cell apoptosis.


KAVAGait: Knowledge-Assisted Visual Analytics for Clinical Gait Analysis.
In 2014, more than 10 million people in the US were affected by an ambulatory disability. Thus, gait rehabilitation is a crucial part of health care systems. The quantification of human locomotion enables clinicians to describe and analyze a patient's gait performance in detail and allows them to base clinical decisions on objective data. These assessments generate a vast amount of complex data which need to be interpreted in a short time period. We conducted a design study in cooperation with gait analysis experts to develop a novel Knowledge-Assisted Visual Analytics solution for clinical Gait analysis (KAVAGait). KAVAGait allows the clinician to store and inspect complex data derived during clinical gait analysis. The system incorporates innovative and interactive visual interface concepts, which were developed based on the needs of clinicians. Additionally, an explicit knowledge store (EKS) allows externalization and storage of implicit knowledge from clinicians. It makes this information available for others, supporting the process of data inspection and clinical decision making. We validated our system by conducting expert reviews, a user study, and a case study. Results suggest that KAVAGait is able to support a clinician during clinical practice by visualizing complex gait data and providing knowledge of other clinicians.


Invariant Valpha14 chain NKT cells promote Plasmodium berghei circumsporozoite protein-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+ T cells in the liver after poxvirus vaccination of mice.
Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-gamma)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Valpha14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Valpha14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Valpha14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-gamma- and tumor necrosis factor alpha (TNF-alpha)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Valpha14iNKT cells secreted interleukin-4 than IFN-gamma. Vaccinated Valpha14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-gamma+ and TNF-alpha+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Valpha14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-gamma+/TNF-alpha+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.


Relational mobility predicts social behaviors in 39 countries and is tied to historical farming and threat.
Biologists and social scientists have long tried to understand why some societies have more fluid and open interpersonal relationships and how those differences influence culture. This study measures relational mobility, a socioecological variable quantifying voluntary (high relational mobility) vs. fixed (low relational mobility) interpersonal relationships. We measure relational mobility in 39 societies and test whether it predicts social behavior. People in societies with higher relational mobility report more proactive interpersonal behaviors (e.g., self-disclosure and social support) and psychological tendencies that help them build and retain relationships (e.g., general trust, intimacy, self-esteem). Finally, we explore ecological factors that could explain relational mobility differences across societies. Relational mobility was lower in societies that practiced settled, interdependent subsistence styles, such as rice farming, and in societies that had stronger ecological and historical threats.


CRM1 Inhibitors for Antiviral Therapy.
Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed. Overexpression of CRM1-mediated nuclear export is evident in several solid and hematological malignancies. Interestingly, CRM1-mediated nuclear export of viral components is crucial in various stages of the viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer and selected viruses. Leptomycin B (LMB) is the prototypical inhibitor of CRM1 potent against various cancer cell lines overexpressing CRM1 and in limiting viral infections at nanomolar concentrations in vitro. However, the irreversible shutdown of nuclear export results in high cytotoxicity and limited efficacy in vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can potentially be developed as broadly active antivirals, some of which are summarized in this review.


Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci.
The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other's expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers. This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation.


A randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services: the Northern Ireland Caries Prevention In Practice (NIC-PIP) trial.
Dental caries is the most common disease of childhood. The NHS guidelines promote preventative care in dental practices, particularly for young children. However, the cost-effectiveness of this policy has not been established. To measure the effects and costs of a composite fluoride intervention designed to prevent caries in young children attending dental services. The study was a two-arm, parallel-group, randomised controlled trial, with an allocation ratio of 1 : 1. Randomisation was by clinical trials unit, using randomised permuted blocks. Children/families were not blinded; however, outcome assessment was blinded to group assessment. The study took place in 22 NHS dental practices in Northern Ireland, UK. The study participants were children aged 2-3 years, who were caries free at baseline. The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years. The control group received the prevention advice alone. The primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were the number of decayed, missing or filled tooth surfaces in primary dentition (dmfs) in caries-active children, the number of episodes of pain, the number of extracted teeth and the costs of care. Adverse reactions (ARs) were recorded. A total of 1248 children (624 randomised to each group) were recruited and 1096 (549 in the intervention group and 547 in the control group) were included in the final analyses. A total of 87% of the intervention children and 85% of control children attended every 6-month visit (p = 0.77). In total, 187 (34%) children in the intervention group converted to caries active, compared with 213 (39%) in the control group [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.64 to 1.04; p = 0.11]. The mean number of tooth surfaces affected by caries was 7.2 in the intervention group, compared with 9.6 in the control group (p = 0.007). There was no significant difference in the number of episodes of pain between groups (p = 0.81). However, 164 out of the total of 400 (41%) children who converted to caries active reported toothache, compared with 62 out of 696 (9%) caries-free children (OR 7.1 95% CI 5.1 to 9.9; p < 0.001). There was no statistically significant difference in the number of teeth extracted in caries-active children (p = 0.95). Ten children in the intervention group had ARs of a minor nature. The average direct dental care cost was £155.74 for the intervention group and £48.21 for the control group over 3 years (p < 0.05). The mean cost per carious surface avoided over the 3 years was estimated at £251.00. The usual limitations of a trial such as generalisability and understanding the underlying reasons for the outcomes apply. There is no mean willingness-to-pay threshold available to enable assessment of value for money. A statistically significant effect could not be demonstrated for the primary outcome. Once caries develop, pain is likely. There was a statistically significant difference in dmfs in caries-active children in favour of the intervention. Although adequately powered, the effect size of the intervention was small and of questionable clinical and economic benefit. Future work should assess the caries prevention effects of interventions to reduce sugar consumption at the population and individual levels. Interventions designed to arrest the disease once it is established need to be developed and tested in practice. Current Controlled Trials ISRCTN36180119 and EudraCT 2009-010725-39. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 71. See the NIHR Journals Library website for further project information.


Experimental results for H2 formation from H- and H and implications for first star formation.
During the epoch of first star formation, molecular hydrogen (H2) generated via associative detachment (AD) of H- and H is believed to have been the main coolant of primordial gas for temperatures below 10(4) kelvin. The uncertainty in the cross section for this reaction has limited our understanding of protogalaxy formation during this epoch and of the characteristic masses and cooling times for the first stars. We report precise energy-resolved measurements of the AD reaction, made with the use of a specially constructed merged-beams apparatus. Our results agreed well with the most recent theoretically calculated cross section, which we then used in cosmological simulations to demonstrate how the reduced AD uncertainty improves constraints of the predicted masses for Population III stars.


Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients.
Higher rates of serious illness and death from coronavirus SARS-CoV-2 (COVID-19) infection among older people and those who have comorbidities suggest that age- and disease-related biological processes make such individuals more sensitive to environmental stress factors including infectious agents like coronavirus SARS-CoV-2. Specifically, impaired redox homeostasis and associated oxidative stress appear to be important biological processes that may account for increased individual susceptibility to diverse environmental insults. The aim of this Viewpoint is to justify (1) the crucial roles of glutathione in determining individual responsiveness to COVID-19 infection and disease pathogenesis and (2) the feasibility of using glutathione as a means for the treatment and prevention of COVID-19 illness. The hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation and death in COVID-19 patients was proposed on the basis of an exhaustive literature analysis and observations. The hypothesis unravels the mysteries of epidemiological data on the risk factors determining serious manifestations of COVID-19 infection and the high risk of death and opens real opportunities for effective treatment and prevention of the disease.


How does a hilly urban environment influence daily physical activity in obese individuals?
Increases in physical activity (PA) are promoted by walking in an outdoor environment. Along with walking speed, slope is a major determinant of exercise intensity, and energy expenditure. The hypothesis was that in free-living conditions, a hilly environment diminishes PA to a greater extent in obese (OB) when compared with control (CO) individuals. To assess PA types and patterns, 28 CO (22 ± 2 kg/m²) and 14 OB (33 ± 4 kg/m²) individuals wore during an entire day 2 accelerometers and 1 GPS device, around respectively their waist, ankle and shoulder. They performed their usual PA and were asked to walk an additional 60 min per day. The duration of inactivity and activity with OB individuals tended to be, respectively, higher and lower than that of CO individuals (P = .06). Both groups spent less time walking uphill/downhill than on the level (20%, 19%, vs. 61% of total walking duration, respectively, P < .001). However OB individuals spent less time walking uphill/downhill per day than CO (25 ± 15 and 38 ± 15 min/d, respectively, P < 0.05) and covered a shorter distance per day (3.8 km vs 5.2 km, P < 0.01). BMI and outdoor topography should also be considered when prescribing extra walking in free-living conditions.


Identifying New Frontiers for Social Media Engagement in Global Surgery: An Observational Study.
The purpose of this observational study is to characterize the use of social media content pertaining to global surgery. A search for public posts on social media related to global surgery was performed over a 3-month window, from January 1st, 2019, to March 31st, 2019. Two public domains were included in the search: Instagram and Twitter. Posts were selected by filtering for one hashtag: #GlobalSurgery. A binary scoring system was used for media format, perspective of the poster, timing of the post, tone, and post content. Data were analyzed using Chi-squared tests with significance set to p < 0.05. Overall, 2633 posts with the hashtag #GlobalSurgery were publicly shared on these two social media platforms over the 3-month period. Of these, 2272 (86.3%) referenced content related to global surgery and were original posts. Physicians and other health professionals authored a majority (60.5%, 1083/1788) of posts on Twitter, whereas organizations comprised a majority of the posts on Instagram (59.9%, 290/484). Posts either had a positive (50.2%, 1140/2272) or neutral (49.6%, 1126/2272) tone, with only 0.3% or 6/2272 of posts being explicitly negative. The content of the posts varied, but most frequently (43.4%, 986/2272) focused on promoting communication and engagement within the community, followed by educational content (21.3%, 486/2272), advertisements (18.8%, 427/2272), and published research (13.2%, 299/2272). The majority of global surgery posts originated from the USA, UK, or Canada (67.6%, 1537/2272), followed by international organizations (11.5%, 261/2272). Chi-squared analysis comparing Instagram with Twitter performed examining media content, tone, perspective, and content, finding statistically significant differences (p < 0.001) the two platforms for each of the categories. The online social media community with respect to global surgery engagement is predominantly composed of surgeons and health care professionals, focused primarily on promoting dialogue within the online community. Social media platforms may provide a scalable tool that can augment engagement between global surgeons, with remaining opportunity to foster global collaboration, community engagement, education and awareness.


Elemental composition in vesicles of an arbuscular mycorrhizal fungus, as revealed by PIXE analysis.
We investigated element accumulation in vesicles of the arbuscular mycorrhizal (AM) fungus Glomus intraradices, extracted from the roots of inoculated leek plants. The elemental composition (elements heavier than Mg) was quantified using particle-induced X-ray emission (PIXE), in combination with scanning transmission ion microscopy (STIM). In vesicles, P was the most abundant of the elements analysed, followed by Ca, S, Si and K. We analysed 12 vesicles from two root systems and found that the variation between vesicles was particularly high for P and Si. The P content related positively to Si, Zn and K, while its relation to Cl fitted to a negative power function. Vesicle transects showed that P and K were present in central parts, while Ca was present mainly near the vesicle surfaces. The results showed that P is an important part (0.5% of the dry weight) of the vesicle content and that the distribution of some elements, within mycelia, may be strongly correlated.


Contrasting effects of anesthetics in tadpole bioassays.
The median anesthetic concentrations (AC 50 values) in the bath solution for loss of righting reflex (RR) or nociceptor response (NR) were determined in larval Rana catesbeiana. The AC50 (NR)/AC50(RR) ratios were between 1.6 and 1.9 for ethanol, ether and diazepam. Comparable ratios for hexobarbital and thiopental were 9.8 and 6.2, which indicated a marked lack of "analgesic" effect. The tadpole AC50 values were consistently higher than AC50 values reported for nonionized and unbound drug in mammalian blood water. The tadpole/mammal ratio for loss of NR during thiopental anesthesia was approximate 8, and analysis of ventricular blood showed that the ultrahigh bath concentrations of thiopental were in equilibrium with those in tadpole serum. The tadpole/mammal ratio for diazepam was approximate 110, and its effect in the tadpole was not reversed by flumazenil. Tadpole/mammal ratios for ethanol and ether were approximate 2. Ethanol and ether showed additive effects when tested in combination, and ethanol-tolerant tadpoles showed a similar tolerance to ether. In contrast, hexobarbital and ethanol showed supra-additive effects, and ethanol-tolerant tadpoles showed a greater tolerance to hexobarbital than to ethanol or ether. These studies show marked differences in effect between barbiturates and the ethanol-ether group, high-concentration benzodiazepine effects presumably independent of a specific receptor, and marked differences in drug potency between amphibia and mammals.


Impact of quality items on study outcome. Treatments in acute lateral ankle sprains.
This study investigates the influence of different aspects of methodologic quality on the conclusions of a systematic review concerning treatments of acute lateral ankle sprain. A data set of a systematic review of 44 trials was used, of which 22 trials could be included in this study. Quality assessment of the individual studies was performed using the Delphi list. We calculated effect sizes of the main outcome measure in each study in order to evaluate the relationship between overall quality scores and outcome. Next, we investigated the impact of design attributes on pooled effect sizes by subgroup analysis. The quality of most studies (82%) was low; only 4 of 22 trials were of high quality. Studies with proper randomization and blinding procedure produce a slightly higher (not statistically significant) effect estimate compared to the other studies. Previous research has suggested that methodologically poorly designed studies tend to over-estimate the effect estimate. Our study does not confirm these conclusions.


Modeling structurally variable regions in homologous proteins with rosetta.
A major limitation of current comparative modeling methods is the accuracy with which regions that are structurally divergent from homologues of known structure can be modeled. Because structural differences between homologous proteins are responsible for variations in protein function and specificity, the ability to model these differences has important functional consequences. Although existing methods can provide reasonably accurate models of short loop regions, modeling longer structurally divergent regions is an unsolved problem. Here we describe a method based on the de novo structure prediction algorithm, Rosetta, for predicting conformations of structurally divergent regions in comparative models. Initial conformations for short segments are selected from the protein structure database, whereas longer segments are built up by using three- and nine-residue fragments drawn from the database and combined by using the Rosetta algorithm. A gap closure term in the potential in combination with modified Newton's method for gradient descent minimization is used to ensure continuity of the peptide backbone. Conformations of variable regions are refined in the context of a fixed template structure using Monte Carlo minimization together with rapid repacking of side-chains to iteratively optimize backbone torsion angles and side-chain rotamers. For short loops, mean accuracies of 0.69, 1.45, and 3.62 A are obtained for 4, 8, and 12 residue loops, respectively. In addition, the method can provide reasonable models of conformations of longer protein segments: predicted conformations of 3A root-mean-square deviation or better were obtained for 5 of 10 examples of segments ranging from 13 to 34 residues. In combination with a sequence alignment algorithm, this method generates complete, ungapped models of protein structures, including regions both similar to and divergent from a homologous structure. This combined method was used to make predictions for 28 protein domains in the Critical Assessment of Protein Structure 4 (CASP 4) and 59 domains in CASP 5, where the method ranked highly among comparative modeling and fold recognition methods. Model accuracy in these blind predictions is dominated by alignment quality, but in the context of accurate alignments, long protein segments can be accurately modeled. Notably, the method correctly predicted the local structure of a 39-residue insertion into a TIM barrel in CASP 5 target T0186.