The interplay of birth weight, dopamine receptor D4 gene (DRD4), and early maternal care in the prediction of disorganized attachment at 36 months of age.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non-seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother-child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non-seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.


Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease.
Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.


Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis.
The fragile X syndrome results from transcriptional silencing of the FMR1 gene and the absence of its encoded FMRP protein. Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, have been identified and the overall structures of the corresponding proteins are very similar to that of FMRP. Using antibodies raised against FXR1P, we observed that two major protein isoforms of relative MW of 78 and 70 kDa are expressed in different mammalian cell lines and in the majority of mouse tissues. In mammalian cells grown in culture as well as in brain extracts, both P78and P70isoforms are associated with mRNPs within translating polyribosomes, similarly to their closely related FMRP homologues. In muscle tissues as well as in murine myoblastic cell lines induced to differentiate into myotubes, FXR1P78and P70isoforms are replaced by novel unpredicted isoforms of 81-84 kDa and a novel FXR1 exon splice variant was detected in muscle RNA. While P81-84isoforms expressed after fusion into myotubes in murine myoblast cell lines grown in culture are associated with polyribosomes, this is not the case when isolated from muscle tissues since they sediment with lower S values. Immunohistochemical studies showed coexpression of FMRP and FXR1P70and P78in the cytoplasm of brain neurons, while in muscle no FMRP was detected and FXR1P81-84were mainly localized to structures within the muscle contractile bands. The complex expression pattern of FXR1P suggests tissue-specific expression for the various isoforms of FXR1 and the differential expression of FMRP and FXR1Ps suggests that in certain types of cells and tissues, complementary functions may be fulfilled by the various FMRP family members.


Assessing the Integrated Community-Based Health Systems Strengthening initiative in northern Togo: a pragmatic effectiveness-implementation study protocol.
Over the past decade, prevalence of maternal and child morbidity and mortality in Togo, particularly in the northern regions, has remained high despite global progress. The causes of under-five child mortality in Togo are diseases with effective and low-cost prevention and/or treatment strategies, including malaria, acute lower respiratory infections, and diarrheal diseases. While Togo has a national strategy for implementing the integrated management of childhood illness (IMCI) guidelines, including a policy on integrated community case management (iCCM), challenges in implementation and low public sector health service utilization persist. There are critical gaps to access and quality of community health systems throughout the country. An integrated facility- and community-based initiative, the Integrated Community-Based Health Systems Strengthening (ICBHSS) initiative, seeks to address these gaps while strengthening the public sector health system in northern Togo. This study aims to evaluate the effect and implementation strategy of the ICBHSS initiative over 48 months in the catchment areas of 21 public sector health facilities. The ICBHSS model comprises a bundle of evidence-based interventions targeting children under five, women of reproductive age, and people living with HIV through (1) community engagement and feedback; (2) elimination of point-of-care costs; (3) proactive community-based IMCI using community health workers (CHWs) with additional services including family planning, HIV testing, and referrals; (4) clinical mentoring and enhanced supervision; and (5) improved supply chain management and facility structures. Using a pragmatic type II hybrid effectiveness-implementation study, we will evaluate the ICBHSS initiative with two primary aims: (1) determine effectiveness through changes in under-five mortality rates and (2) assess the implementation strategy through measures of reach, adoption, implementation, and maintenance. We will conduct a mixed-methods assessment using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. This assessment consists of four components: (1) a stepped-wedge cluster randomized control trial using a community-based household survey, (2) annual health facility assessments, (3) key informant interviews, and (4) costing and return-on-investment assessments for each randomized cluster. Our research is expected to contribute to continuous quality improvement initiatives, optimize implementation factors, provide knowledge regarding health service delivery, and accelerate health systems improvements in Togo and more broadly. ClinicalTrials.gov , NCT03694366 , registered 3 October 2018.


Temporomandibular disorders after whiplash injury: a controlled, prospective study.
Whiplash injury to the neck is often considered a significant risk factor for development of temporomandibular disorders (TMD), and has been proposed to produce internal derangements of the temporomandibular joint (TMJ). Few studies, however, have examined TMD-related pain in acute whiplash patients compared with a matched control group. The aim of the present study was to assess pain and sensorimotor function in the craniofacial region in an unselected group of patients sustaining a motor vehicle accident involving a rear collision. Prospectively, 19 acute whiplash patients exposed to a motor vehicle accident involving a rear collision participated in a study of TMD. The control group consisted of 20 age- and gender-matched ankle-injury patients. Participants were seen within 4 weeks and again at 6 months post-injury. The masticatory system was examined in accordance with the research diagnostic criteria. Participants underwent structured interviews, filled out the McGill Pain Questionnaire (MPQ), and had their masticatory system examined by a trained dentist, blinded to their diagnosis. Pain detection threshold (PDT) to pressure stimuli, and maximal voluntary occlusal force (MVOF) were obtained at each visit. One whiplash patient and 1 ankle-injury patient had jaw pain at the first visit. Palpation scores of the TMJ and the summated palpation scores only tended to be higher in patients sustaining a whiplash injury than in ankle-injury controls at the first visit. However, MPQ, TMD symptoms and signs, MVOF and PDT were not significantly different in whiplash-injury and ankle-injury patients after 4 weeks and 6 months. TMD pain after whiplash injury and ankle injury is rare, suggesting that whiplash injury is not a major risk factor for the development of TMD problems. Further studies are needed to identify which other factors may contribute to TMD pain.


Effect of strigolactone on growth, photosynthetic efficiency, antioxidant activity, and osmolytes accumulation in different maize (Zea mays L.) hybrids grown under drought stress.
Drought alters plant physiology, morphology, and biochemical pathways, necessitating effective mitigation strategies. Strigolactones (SLs) are phytohormones known to enhance plant growth under abiotic stress. However, their specific impact on drought stress in maize remains unclear. This study aimed to determine the optimal SL concentration for mitigating drought stress in two maize hybrids (HY-1898, FH-1046). Maize plants were subjected to 60% field capacity drought stress in a pot experiment. After 40 d, different concentrations (0, 0.001, 0.01, and 0.1 mg L-1) of the synthetic SL analogue GR24 were applied to evaluate their effects on growth features, photosynthesis attributes, and osmolyte accumulation in the maize hybrids. Results showed that exogenous SL application significantly increased photosynthetic pigments in maize hybrids under drought stress. Chlorophyll content, gas exchange characteristics, net CO2 assimilation rate, stomatal conductance, water use efficiency, and antioxidant activities were enhanced by GR24. Leaf ascorbic acid and total phenolics also increased with SL application. Organic osmolytes, such as glycine betaine and free proline, were elevated in both maize hybrids under drought stress. Yield-related parameters, including cob diameter, cob weight, number of seeds per cob, and number of seeds per plant, were significantly increased by GR24 under drought stress. Our findings highlight the potential of GR24 foliar application to mitigate drought stress and promote maize growth and grain yield in a concentration-dependent manner. The minimum effective SL concentration against drought stress was determined to be 0.01 mg L-1. Overall, foliar application of GR24 could serve as a sustainable approach for drought tolerance in agriculture.


Lack of effectiveness of botulinum neurotoxin A on isolated detrusor strips and whole bladders from mice and guinea-pigs in vitro.
To differentiate between the effects of parasympathetic and sensorimotor stimulation of isolated mouse and guinea-pig bladders in vitro by measuring the pressure increases to electrical field stimulation (EFS) and then comparing the effects of botulinum neurotoxin A (BoNT-A) applied either to the lumen or to the external bathing medium. Isolated mouse and guinea-pig bladders and detrusor strips were exposed to EFS in vitro before and after the addition of BoNT-A. The rationale of this method was that BoNT-A applied to the outside of the bladder would first affect the parasympathetic nerves before diffusing inwards to affect the sensorimotor innervation. BoNT-A applied intravesically would first reach the sensorimotor nerves and only later the parasympathetic nerves. Initial experiments on strips of detrusor were conducted to establish the correct dosage and application time of BoNT-A. Contrary to our expectations, BoNT-A application failed to produce any significant effects on either the detrusor strips or whole bladders. Our experimental design failed to show any effect of BoNT-A on the contractility of detrusor muscle strips or whole bladders from mice and guinea-pigs. The reason for this is unclear, but may be related to tissue spending inadequate time incubated with BoNT-A under physiological conditions.


Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.
In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination. We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1β in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines. A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users. These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets.


Vascular renin-angiotensin system and neurotransmission in hypertensive persons.
The existence of a vascular renin-angiotensin system and its role in modulating sympathetic activity were evaluated in forearm arterioles of hypertensive individuals. Isoproterenol (0.03, 0.01, 0.3 microgram/100 ml/min for 5 minutes each; n = 5) was infused into the brachial artery, and active and inactive renin, angiotensin II, and norepinephrine forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Isoproterenol caused vasodilation and a dose-dependent active and inactive renin, angiotensin II, and norepinephrine outflow, an effect blunted by propranolol (10 micrograms/100 ml/min). To evaluate the role of local angiotensin II on beta-mediated norepinephrine overflow, the experiment was repeated with captopril (2.5 micrograms/100 ml/min for 10 minutes; n = 5), which abolished angiotensin II release and significantly reduced norepinephrine overflow. To test whether angiotensin II facilitates both prejunctional norepinephrine release and its postjunctional action, we evaluated the effect of exogenous angiotensin II, infused into the brachial artery at low concentrations (0.001 microgram/100 ml/min), on forearm vasoconstriction and norepinephrine release induced by endogenous sympathetic activation (application of a lower body negative pressure: -10 and -20 mm Hg for 5 minutes, n = 10) and on the vasoconstrictor effect of local norepinephrine (0.0015, 0.005, 0.015, 0.05, 0.15 micrograms/100 ml/min for 3 minutes each; n = 6). Although angiotensin II increased the vasoconstricting effect and the norepinephrine release induced by lower body negative pressure, it failed to affect norepinephrine-mediated vasoconstriction. Our data indicate the existence in hypertensive individuals of a vascular renin-angiotensin system that seems to modulate sympathetic activity through the presynaptic facilitation of norepinephrine release.


Finish line plant-insect interactions mediated by insect feeding mode and plant interference: a case study of Brassica interactions with diamondback moth and turnip aphid.
There are gaps in our understanding of plant responses under different insect phytophagy modes and their subsequent effects on the insect herbivores' performance at late season. Here we compared different types of insect feeding by an aphid, Lipaphis erysimi, and a lepidopteran, Plutella xylostella, and how this affected defensive metabolites in leaves of 2 Brassica species when plants gain maturity. Thiocyanate concentrations after P. xylostella and L. erysimi feeding activities were the same. Total phenolics was higher after the phloem feeder feeding than the folivore activity. The plants compensatory responses (i.e., tolerance) to L. erysimi feeding was significantly higher than the responses to P. xylostella. This study showed that L. erysimi had higher carbon than P. xylostella whereas nitrogen in P. xylostella was 1.42 times that in L. erysimi. Population size of the phloem feeder was not affected by plant species or insect coexistence. However, there was no correlation between plant defensive metabolites and both insects' population size and biomass. This suggests that plant root biomass and tolerance index after different insect herbivory modes are not necessarily unidirectional. Importantly, the interaction between the folivore and the phloem feeder insects is asymmetric and the phloem feeder might be a trickier problem for plants than the folivore. Moreover, as both plants' common and special defenses decreased under interspecific interference, we suggest that specialist insect herbivores can be more challenged in ecosystems in which plants are not involved in interspecific interference.


The calcium/calmodulin-dependent phosphodiesterase PDE1C down-regulates glucose-induced insulin secretion.
To understand the role cAMP phosphodiesterases (PDEs) play in the regulation of insulin secretion, we analyzed cyclic nucleotide PDEs of a pancreatic beta-cell line and used family and isozyme-specific PDE inhibitors to identify the PDEs that counteract glucose-stimulated insulin secretion. We demonstrate the presence of soluble PDE1C, PDE4A and 4D, a cGMP-specific PDE, and of particulate PDE3, activities in betaTC3 insulinoma cells. Selective inhibition of PDE1C, but not of PDE4, augmented glucose-stimulated insulin secretion in a dose-dependent fashion thus demonstrating that PDE1C is the major PDE counteracting glucose-dependent insulin secretion from betaTC3 cells. In pancreatic islets, inhibition of both PDE1C and PDE3 augmented glucose-dependent insulin secretion. The PDE1C of betaTC3 cells is a novel isozyme possessing a K(m) of 0.47 microM for cAMP and 0.25 microM for cGMP. The PDE1C isozyme of betaTC3 cells is sensitive to 8-methoxymethyl isobutylmethylxanthine and zaprinast (IC(50) = 7.5 and 4.5 microM, respectively) and resistant to vinpocetine (IC(50) > 100 microM). Increased responsiveness of PDE1C activity to calcium/calmodulin is evident upon exposure of cells to glucose. Enhanced cAMP degradation by PDE1C, due to increases in its responsiveness to calcium/calmodulin and in intracellular calcium, constitutes a glucose-dependent feedback mechanism for the control of insulin secretion.


Longitudinal persistence with secondary prevention therapies relative to patient risk after myocardial infarction.
Prior studies have demonstrated that patients with high-risk acute myocardial infarction (AMI) are less likely to receive guideline-directed medications during hospitalisation. It is unknown if this paradox persists following discharge. We aimed to assess if persistence with guideline-directed medications post discharge varies by patients' risk following AMI. Data were analysed from two prospective, multicentre US AMI registries. The primary outcome was persistence with all prescribed guideline-directed medications (aspirin, β-blockers, statins, angiotensin-antagonists) at 1, 6 and 12 months post discharge. The association between risk and medication persistence post discharge was assessed using multivariable mixed-effect models. Among 6434 patients with AMI discharged home, 2824 were considered low-risk, 2014 intermediate-risk and 1596 high-risk for death based upon their Global Registry of Acute Coronary Event (GRACE) 6-month risk score. High-risk was associated with a lower likelihood of receiving all appropriate therapies at discharge compared with low-risk patients (relative risk (RR) 0.90; 95% CI 0.87 to 0.94). At 12 months, the rate of persistence with all prescribed therapies was 61.5%, 57.9% and 45.9% among low-risk, intermediate-risk and high-risk patients, respectively. After multivariable adjustment, high-risk was associated with lower persistence with all prescribed medications (RR 0.87; 95% CI 0.82 to 0.92) over follow-up. Similar associations were seen for individual medications. Over the 5 years of the study, persistence with prescribed therapies post discharge improved modestly among high-risk patients (RR 1.05; 95% CI 1.03 to 1.08 per year). High-risk patients with AMI have a lower likelihood of persistently taking prescribed medications post discharge as compared with low-risk patients. Continued efforts are needed to improve the use of guideline-directed medications in high-risk patients.


High-resolution two-dimensional electrophoretic analysis of acidic, basic and surface proteins of mouse neutrophils.
The proteins from murine neutrophils have been examined using isoelectric focusing and non-equilibrium pH gradient electrophoresis in the first dimension and sodium dodecyl sulfate-polyacrylamide electrophoresis as a second dimension. The major protein, actin, dominates the protein profiles and it appears to be one of the few proteins being synthesised rapidly. In the presence of protease inhibitors, neutrophil (a homogeneous, non-dividing cell population) lysates gave extremely reproducible two-dimensional electrophoretic patterns both with Coomassie blue staining (approx. 20 proteins detected) and with fluorography or autoradiography after [35S]methionine biosynthetic labelling (approx. 450 proteins detected between pH 4 and 7). Biosynthetic labelling was more sensitive than protein staining for some components, although the mature neutrophils did not synthesis certain cellular proteins (e.g., granule proteins such as lactoferrin). Surface labelling of neutrophils (as indicated by the absence of 125I associated with actin) yielded more than 20 major 125I-labelled proteins on high-resolution electrophoretic maps. The major 125I-labeled protein (Mr approximately 90 kdalton) focused at the acidic end of the gels near pH 4.1. This protein could also be detected after [35S]methionine biosynthetic labelling. All of the high molecular weight components focused over a broad pH range (0.2 pH units). At lease one of the surface components appeared to consist of several discrete charge entities.


Head postures during naturalistic driving.
A rotated head posture at the time of a rear-end impact is associated with a higher risk of acute and chronic whiplash injury. The objective of this study was to quantify the amplitude and duration of rotated head postures observed in drivers during naturalistic driving. Twenty volunteers (14 males: 36 ± 12 years, 6 females: 27 ± 5 years) drove a 2010 Subaru Impreza on public roads while their 3D head angular position relative to the car was recorded using inertial measurement units. An experimenter rode in the passenger seat (right side) and logged when subjects performed one of 6 head movements: Bilateral shoulder and side mirror checks, looking at the rearview mirror, and looking at the front seat passenger. Video of the subjects was used to confirm the logged head movements and identify movements that the experimenter missed. The duration and amplitude of all 6 head movements were tabulated and then compared between periods when the car was moving and when the car was stationary. During a 68 ± 5-min drive, subjects performed a median (range) of 15 (5-39) left shoulder checks, 82.5 (29-167) left mirror checks, 40.5 (10-168) rearview mirror checks, 27.5 (3-113) right mirror checks, 60 (0-185) passenger looks, and 12.5 (1-28) right shoulder checks. Peak yaw angles of the head relative to the vehicle for these 6 movements averaged -81.5°, -34.3°, 16.2°, 42.1°, 58.2°, and 84.3°, respectively. Drivers spent a larger proportion of time in nonneutral postures when the vehicle was stopped (17.5%) compared to moving (8.2%) (Z = 3.92, P < .0001). Drivers also moved their head further from neutral during the movements when the car was stationary compared to moving (t19 = 5.90, P < .0001). Drivers use larger and longer duration head movements when stationary than when driving. Given an increased risk of whiplash injury for initially rotated head postures, these findings provide a possible explanation for why drivers are more likely to be injured when hit from behind while their vehicle is stationary. Further, the head postures characterized in this study can be used as initial conditions in volunteer and computational studies to improve our understanding of why nonneutral head postures are associated with increased whiplash injury risk.


Steroid sulfatase: molecular biology, regulation, and inhibition.
Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and therefore has a pivotal role in regulating the formation of biologically active steroids. The enzyme is widely distributed throughout the body, and its action is implicated in physiological processes and pathological conditions. The crystal structure of the enzyme has been resolved, but relatively little is known about what regulates its expression or activity. Research into the control and inhibition of this enzyme has been stimulated by its important role in supporting the growth of hormone-dependent tumors of the breast and prostate. STS is responsible for the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone, respectively, both of which can be converted to steroids with estrogenic properties (i.e., estradiol and androstenediol) that can stimulate tumor growth. STS expression is increased in breast tumors and has prognostic significance. The role of STS in supporting tumor growth prompted the development of potent STS inhibitors. Several steroidal and nonsteroidal STS inhibitors are now available, with the irreversible type of inhibitor having a phenol sulfamate ester as its active pharmacophore. One such inhibitor, 667 COUMATE, has now entered a phase I trial in postmenopausal women with breast cancer. The skin is also an important site of STS activity, and deficiency of this enzyme is associated with X-linked ichthyosis. STS may also be involved in regulating part of the immune response and some aspects of cognitive function. The development of potent STS inhibitors will allow investigation of the role of this enzyme in physiological and pathological processes.


Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein.
Increased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the presence of a receptor-binding protein (RBP), which facilitates host-cell attachment and plays a fundamental role in determining host range. Here, we study the RBP presented on the surface of rodent-borne paramyxoviruses Mossman and Nariva (MosV and NarV, respectively), viruses that constitute founding members of the recently defined Narmovirus genus within the Paramyxoviridae family. Crystallographic analysis of the C-terminal head region of the dimeric MosV and NarV RBPs demonstrates that while these glycoproteins retain the canonical six-bladed β-propeller fold found in other paramyxoviral RBPs, they lack the structural motifs associated with established paramyxovirus host-cell receptor entry pathways. Consistent with MosV-RBP and NarV-RBP undergoing a distinct entry pathway from other characterized paramyxoviruses, structure-based phylogenetic analysis demonstrates that these six-bladed β-propeller head domains form a singular structural class that is distinct from other paramyxoviral RBPs. Additionally, using an integrated crystallographic and small-angle X-ray scattering analysis, we confirm that MosV-RBP and NarV-RBP form homodimeric arrangements that are distinct from those adopted by other paramyxovirus RBPs. Altogether, this investigation provides a molecular-level blueprint of the narmovirus RBP that broadens our understanding of the structural space and functional diversity available to paramyxovirus RBPs. IMPORTANCE Genetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genus Narmovirus, family Paramyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely, a six-bladed β-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses.


Rapid child growth raises blood pressure in adolescent boys who were thin at birth.
Catch-up growth in previously growth-restricted children is a suggested risk factor for chronic disease risk. We use data from 2026 Filipino adolescents to identify periods of growth that matter more for risk of high blood pressure (BP). Subjects were drawn from the Cebu Longitudinal Health and Nutrition Survey, which enrolled pregnant women and followed up their offspring through age 14 to 16 years. High BP was defined as the top 10% of residuals from gender-specific regressions of systolic and diastolic BP on age and height. After controlling for birth length, current body mass index, age, and height, the odds of high BP in males were significantly decreased with each kilogram increase in birth weight. The highest odds of elevated BP occurred among males who were relatively thin at birth but relatively heavy as adolescents. Larger weight increments from birth to 2 years decreased the odds of high BP in boys, whereas larger increments from 8 to 11 and 11 to 16 years increased the odds of high BP. Thinness at birth significantly interacted with growth rate after age 8, such that a high rate of weight gain increased risk only among boys who were in the lower two thirds of the body mass index distribution at birth. Results in girls indicated small or no effects of early growth. The synergistic effect on adolescent BP of rapid weight gain from late childhood into adolescence with thinness at birth is further evidence of fetal programming of BP in males and suggests long-term health risks associated with rapid growth, even in the absence of obesity.


Management of hip fracture.
Hip fracture poses a significant global challenge both to healthcare systems and to patients themselves. We outline the management of this injury, highlight areas where the evidence is deficient and discuss research efforts towards improving the quality of the evidence base. We searched MEDLINE, PubMed and the Cochrane Library, using the core search terms 'hip fracture' and 'proximal femoral fracture'. In addition we reviewed national treatment guidelines for hip fracture care and references from relevant articles. Only articles published in English from inception to March 2015 were included. Modern hip fracture management should consist of a coordinated multidisciplinary approach with orthogeriatrician input, early surgery, adequate analgesia and liaison with related services to facilitate safe supported discharge. The optimum thromboprophylaxis to reduce venous thromboembolism remains a topic for debate. The use of bone cement has received much attention recently with concerns about its safety in the frailest of hip fracture patients. An increasing understanding of the severity and impact of sustaining a hip fracture upon quality of life. Strategies to improve postoperative mobility, postoperative nutrition and the role of home-based rehabilitation. There is a need to identify the optimum analgesic regimes and assessment tools for hip fracture patients with cognitive impairment.


The Neural Implementation of Surgical Expertise Within the Mirror-Neuron System: An fMRI Study.
Motor expertise is an important aspect of high-level performance in professional tasks such as surgery. While recently it has been shown that brain activation as measured by functional magnetic resonance imaging (fMRI) within the mirror-neuron system (MNS) is modulated by expertise in sports and music, little is known about the neural underpinnings of professional, e.g., surgical expertise. Here, we investigated whether and (if so) how surgical expertise is implemented in the MNS in medical professionals across three levels of surgical qualification. In order to answer the more specific research question, namely, if the neural implementation of motor expertise develops in a linear or non-linear fashion, the study compares not only brain activation within the MNS related to action observation of novices and experts, but also intermediates. Ten novices (medical students), ten intermediates (residents in orthopedic surgery) and ten experts (orthopedic surgeons) watched 60 video clips (5 s each) of daily-life activities and surgical procedures each while their brain activation was measured using a 3-T fMRI scanner. An established localization procedure was followed to functionally define the MNS for each participant individually. A 2 (video type: daily-life activities, surgical procedures) × 3 (expertise level: novice, intermediate, expert) ANOVA yielded a non-significant interaction. Furthermore, separate analyses of the precentral and parietal part of the MNS also yielded non-significant interactions. However, post hoc comparisons showed that intermediates displayed marginally significantly lower brain activation in response to surgery-related videos within the MNS than novices. No other significant differences were found. We did not find evidence for the hypothesis that the brain-activation level in the MNS evoked by observing surgical videos reflects the level of surgical expertise in the professional task of (orthopedic) surgery. However, the results suggest a potential non-linear relationship between expertise level and MNS-activation level.


Tandem high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation for recurrent soft tissue sarcoma.
Patients with recurrent soft tissue sarcoma (STS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDC) with hematopoietic stem cell support in this disease has not been established. We report on two patients with recurrent STS who were treated with tandem HDC supported by autologous peripheral blood stem cell transplantation (PBSCT). One patient with malignant fibrous histiocytoma recurred with multiple lung metastases. This patient achieved a partial response after two cycles of induction chemotherapy consisting of ifosfamide and epirubicin. During four cycles of induction chemotherapy, peripheral blood stem cells (PBSCs) were harvested. Tandem high-dose ICE regimen (ifosfamide 3 g/m2 on days-7 to -3, carboplatin 400 mg/m2 on days-7, -5 and 3, etoposide 500 mg/m2 on days-7, -5 and 3) supported by autologous PBSCT gave rise to further regression of the tumors. Another patient with malignant hemangiopericytoma was treated by tandem high-dose ICE regimen supported by autologous PBSCT after the 3rd removal of abdominal tumors. Relapse-free intervals until the 1st, 2nd and 3rd relapses were 40, 19 and 22 months, respectively. Tandem high-dose ICE regimen might delay the relapse. These observations suggest that a tandem high-dose ICE regimen with autologous PBSCT is feasible with some clinical efficacy in the control of refractory STS.


Both Lymantria dispar nucleopolyhedrovirus enhancin genes contribute to viral potency.
Enhancins are a group of proteins first identified in granuloviruses (GV) that have the ability to enhance nuclear polyhedrosis virus potency. We had previously identified an enhancin gene (E1) in the Lymantria dispar multinucleocapsid nucleopolyhedrovirus (LdMNPV) (D. S. Bischoff and J. M. Slavicek, J. Virol. 71:8133-8140, 1997). Inactivation of the E1 gene product within the viral genome lowered viral potency by an average of 2.9-fold. A second enhancin gene (E2) was identified when the entire genome of LdMNPV was sequenced (Kuzio et al., Virology 253:17-34, 1999). The E2 protein exhibits approximately 30% amino acid identity to the LdMNPV E1 protein as well as the enhancins from Trichoplusia ni GV, Pseudaletia unipuncta GV, Helicoverpa armigera GV, and Xestia c-nigrum GV. Northern analysis of viral RNA indicated that the E2 gene transcripts are expressed at late times postinfection from a consensus baculovirus late promoter. The effect of the enhancin proteins on viral potency was investigated through bioassay using two recombinant viruses, one with a deletion in the E2 gene (E2del) and a second with deletion mutations in both enhancin genes (E1delE2del). The enhancin gene viral constructs were verified by Southern analysis and shown not to produce enhancin gene transcripts by Northern analysis. The E2del virus exhibited an average decrease in viral potency of 1.8-fold compared to wild-type virus. In the same bioassays, the recombinant virus E1cat, which does not produce an E1 gene transcript, exhibited an average decrease in viral potency of 2.3-fold compared to control virus. The E1delE2del virus exhibited an average decrease in viral potency of 12-fold compared to wild-type virus. Collectively, these results suggest that both LdMNPV enhancin genes contribute to viral potency, that each enhancin protein can partially compensate for the lack of the other protein, and that both enhancin genes are necessary for wild-type viral potency.


Evolution and proximate expression of human paternal investment.
In more than 95% of mammalian species, males provide little direct investment in the well-being of their offspring. Humans are one notable exception to this pattern and, to date, the factors that contributed to the evolution and the proximate expression of human paternal care are unexplained (T. H. Clutton-Brock, 1989). The nature, extent, and influence of human paternal investment on the physical and social well-being of children are reviewed in light of the social and ecological factors that are associated with paternal investment in other species. On the basis of this review, discussion of the evolution and proximate expression of human paternal investment is provided.


Effects of occupational exposure to chlorpyrifos on neuropsychological function: a prospective longitudinal study.
Exposure to chlorpyrifos (CPF), an organophosphorus (OP) anticholinesterase insecticide, occurs typically in settings where multiple agents are present (e.g., agriculture) and quantitative dose measures may be absent (e.g., pesticide application). Such exposures allow few opportunities to study potential neurobehavioral effects of CPF alone. We studied the relationship between CPF exposure and behavioral function among CPF manufacturing workers, which allowed identification, measurement, and estimation of exposure and important non-exposure variables that potentially could affect study findings. A prospective longitudinal study design was used to compare neurobehavioral function over a one-year period among 53 CPF workers and 60 referent workers. Quantitative and qualitative measures were used, and potential confounders were identified and tested for possible inclusion in our statistical models. Neurobehavioral function was assessed by neuropsychological tests covering various behavioral domains that may be adversely affected by exposure to CPF in sufficient amount. CPF workers had significantly greater CPF exposures during the study period than did referents at levels where physiologic effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<0.0001) and lower average BuChE activity (p<0.01). No evidence for impaired neurobehavioral domains by either group of workers was observed at baseline, on repeat examination, or between examinations. CPF workers scored higher than referent workers on the verbal memory domain score (p=0.03) at baseline, but there were no significant changes in verbal memory over time and no significant group-by-time interactions. The study provides important information about CPF exposure in the workplace by not supporting our working hypothesis that CPF exposure associated with various aspects of the manufacturing process would be accompanied by adverse neurobehavioral effects detectable by quantitative neurobehavioral testing. Some aspects making this workplace site attractive for study and also present limitations for the generalization of results to other situations that might have exposures that vary widely between and within different facilities and locations. For example, these results might not apply to occupations such as applicators with higher exposure or to workers with low educational levels.


Diffusion of a Distress Management Guideline into practice.
The purpose of this study was to explore system and clinician-related barriers, and predictors for the adoption of the National Comprehensive Cancer Network Distress Management Guideline (DMG) into oncology outpatient practice. This descriptive, correlational study surveyed a national sample of oncology nurses working in an outpatient setting who completed the survey electronically or by mail. Study respondents (n = 409) were predominantly certified nurses (84%) yet largely unfamiliar with the DMG; 17% of respondents were using the DMG. Time, staff uncertainties and ambiguous accountability were the largest barriers to not assessing distress. Compared with those not using any assessment tool, those using the DMG were more comfortable discussing distress, worked as an oncology nurse longer, scored colleagues higher on valuing distress screening and had more organizational processes in place to support evidence-based practices. Significant predictors of DMG use included higher familiarity with the DMG (OR 3.81, p < .001), lower perceived barriers (OR 0.41, p = .001), non-profit status (OR 3.93, p = .05) and urban or rural (versus suburban) work settings (OR 04.59, p = .04; overall model chi-square 133.25, df 12, p < .001, Nagelkerke R(2) .67). This study identified barriers and predictors to using the DMG, which are amenable to interventions. DMG adoption may be augmented by interventions, which increase familiarity with the guideline. Additionally, adoption of the DMG may improve through explicit articulation of the responsibilities oncology team members have in cancer-related distress screening and management. Further studies are needed to evaluate the efficacy of such interventions and their impact on patient care outcomes.


Insights into the Clp/HSP100 chaperone system from chloroplasts of Arabidopsis thaliana.
HSP100 proteins are molecular chaperones involved in protein quality control. They assist in protein (un)folding, prevent aggregation, and are thought to participate in precursor translocation across membranes. Caseinolytic proteins ClpC and ClpD from plant chloroplasts belong to the HSP100 family. Their role has hitherto been investigated by means of physiological studies and reverse genetics. In the present work, we employed an in vitro approach to delve into the structural and functional characteristics of ClpC2 and ClpD from Arabidopsis thaliana (AtClpC2 and AtClpD). They were expressed in Escherichia coli and purified to near-homogeneity. The proteins were detected mainly as dimers in solution, and, upon addition of ATP, the formation of hexamers was observed. Both proteins exhibited basal ATPase activity (K(m), 1.42 mm, V(max), 0.62 nmol/(min × μg) for AtClpC2 and K(m) ∼19.80 mm, V(max) ∼0.19 nmol/(min × μg) for AtClpD). They were able to reactivate the activity of heat-denatured luciferase (∼40% for AtClpC2 and ∼20% for AtClpD). The Clp proteins tightly bound a fusion protein containing a model transit peptide. This interaction was detected by binding assays, where the chaperones were selectively trapped by the transit peptide-containing fusion, immobilized on glutathione-agarose beads. Association of HSP100 proteins to import complexes with a bound transit peptide-containing fusion was also observed in intact chloroplasts. The presented data are useful to understand protein quality control and protein import into chloroplasts in plants.


Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head.
To develop an automated approach for segmenting the neural canal opening (NCO) and cup at the level of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex in spectral-domain optical coherence tomography (SD-OCT) volumes. To investigate the correspondence and discrepancy between the NCO-based metrics and the clinical disc margin on fundus photographs of glaucoma subjects. SD-OCT scans and corresponding stereo fundus photographs of the optic nerve head were obtained from 68 eyes of 34 patients with glaucoma or glaucoma suspicion. Manual planimetry was performed by three glaucoma experts to delineate a reference standard (RS) for cup and disc margins from the images. An automated graph-theoretic approach was used to identify the NCO and cup. NCO-based metrics were compared with the RS. Compared with the RS disc margin, the authors found mean unsigned and signed border differences of 2.81 ± 1.48 pixels (0.084 ± 0.044 mm) and -0.99 ± 2.02 pixels (-0.030 ± 0.061 mm), respectively, for NCO segmentation. The correlations of the linear cup-to-disc (NCO) area ratio, disc (NCO) area, rim area, and cup area of the algorithm with the RS were 0.85, 0.77, 0.69, and 0.83, respectively. In most eyes, the NCO-based 2D metrics, as estimated by the novel automated graph-theoretic approach to segment the NCO and cup at the level of the RPE/BM complex in SD-OCT volumes, correlate well with RS. However, a small discrepancy exists in NCO-based anatomic structures and the clinical disc margin of the RS in some eyes.


The impact of malodour on communities: a review of assessment techniques.
Malodours remain the biggest source of complaints regarding environmental issues. This factor is likely to increase, as the urban development steadily encroaches into areas that have malodourous emitting industries (such as wastewater and waste management operations and intensive livestock practices), and has the potential to be both time and fiscally expensive. Despite the enormous amount of research involved in odour detection and abatement, as well as the creation of several distinct methodologies, there has yet been no definitive procedure to evaluate odour impact on communities, as well as community response. This paper is a review of the current methods that explore this problem, as well as a précis of this research field's goals and challenges. The first aim of this review is to illustrate the dichotomy between regulatory-established procedures, such as panellist testing, and methods that are centred around producing a more comprehensive explanation of factors that influence an odour's impact on a community or individual. In that regard, we have addressed several predominant paradigms of inquiry for this field: analytical methods, panellist testing, qualitative research, and survey methods, with associated variants. Secondly, the challenges of measuring and monitoring community impact are discussed. While the quantification of odorants is crucial to appreciating impact, individual-based modifiers of perception have an enormous scope for which to shape the effect of those odours. Perceptual differences are also likely the most dominant variables that influence the elicited behaviour of individuals who have experienced malodour exposure.


CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation.
Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase involved in cell growth and transformation. Here we report the identification by yeast interaction trap of a CK2 interacting protein, UBC3B, which is highly homologous to the E2 ubiquitin conjugating enzyme UBC3/CDC34. UBC3B complements the yeast cdc34-2 cell cycle arrest mutant in S. cerevisiae and transfers ubiquitin to a target substrate in vitro. UBC3B is specifically phosphorylated by CK2 in vitro and in vivo. We mapped by deletions and site directed mutagenesis the phosphorylation site to a serine residue within the C-terminal domain in position 233 of UBC3B and in the corresponding serine residue of UBC3. Following CK2-dependent phosphorylation both UBC3B and UBC3 bind to the F-box protein beta-TrCP, the substrate recognition subunit of an SCF (Skp1, Cul1, F-box) ubiquitin ligase. Furthermore, we observed that co-transfection of CK2alpha' together with UBC3B, but not with UBC3DeltaC, enhances the degradation of beta-catenin. Taken together these data suggest that CK2-dependent phosphorylation of UBC3 and UBC3B functions by regulating beta-TrCP substrate recognition.


A neural model of valuation and information virality.
Information sharing is an integral part of human interaction that serves to build social relationships and affects attitudes and behaviors in individuals and large groups. We present a unifying neurocognitive framework of mechanisms underlying information sharing at scale (virality). We argue that expectations regarding self-related and social consequences of sharing (e.g., in the form of potential for self-enhancement or social approval) are integrated into a domain-general value signal that encodes the value of sharing a piece of information. This value signal translates into population-level virality. In two studies (n = 41 and 39 participants), we tested these hypotheses using functional neuroimaging. Neural activity in response to 80 New York Times articles was observed in theory-driven regions of interest associated with value, self, and social cognitions. This activity then was linked to objectively logged population-level data encompassing n = 117,611 internet shares of the articles. In both studies, activity in neural regions associated with self-related and social cognition was indirectly related to population-level sharing through increased neural activation in the brain's value system. Neural activity further predicted population-level outcomes over and above the variance explained by article characteristics and commonly used self-report measures of sharing intentions. This parsimonious framework may help advance theory, improve predictive models, and inform new approaches to effective intervention. More broadly, these data shed light on the core functions of sharing-to express ourselves in positive ways and to strengthen our social bonds.


Venereology in India.
Venereology-the study of venereal diseases or more recently, the sexually transmitted infections (STI) includes a variety of pathogens namely viruses, bacteria, fungi and protozoa for which the common factor is the mode of transmission and acquisition: Sexual relations between human beings. Medical and other historians have often suggested that well-known diseases such as syphilis, gonorrhea, chancroid and lymphogranuloma venereum have existed since earliest times. However, it is difficult to identify modern disease entities based on written historical record. Studying the origin of STIs helps us to learn the political, economic and moral conditions that led to the disease. Effective management of STI rests on three pillars of diagnosis, prevention and treatment. For most of past 50 years in India, the diagnostic pillar has been the least well-supported. Until well into present century, diagnosis of STI in India was clinical. Treatment of STIs in India followed the methods used in England. Of course in the 19(th) century, in many parts of the world, only a few had access to modern methods of treatment; in India, there was extensive use of Ayurvedic treatment with traditional medicines. This article thus gives just an overview and evolution of venereology in India with regard to venereal diseases (now more often known as STIs/disease), control measures, academic, association and journal development and finally future perspective.


Clearance Prediction of HIV Protease Inhibitors in Man: Role of Hepatic Uptake.
The aim of this work was to explore the contribution of the organic anion transporting polypeptide-1B (OATP1B) drug transporters in the hepatic clearance (Cl) of all marketed HIV protease inhibitors (PI) in humans. HIV PI uptake rates in OATP1B1/1B3-transfected Chinese hamster ovary cells were converted to uptake Cl values in human hepatocytes via a relative activity factor, which was determined by comparing uptake of known substrates between OATP1B1/3-transfected cells and human hepatocytes. Metabolic Cl values were determined in human liver microsomes. In vivo hepatic Cl values were calculated either by combining drug uptake and metabolism or based on one of these individual Cl processes and compared with published in vivo hepatic Cl values. Excellent in vitro-in vivo correlation (R(2) = 0.85) was observed when only uptake Cl values were used, but not when only metabolic Cl was used (R(2) = 0.40). The correlation did not improve when both processes were taken into account (R(2) = 0.85). PBPK models confirmed the remarkable sensitivity of predicted exposure to hepatic drug uptake, indicating a key role for OATP1B1/3 in hepatic disposition of several HIV PI in man. This may contribute to the interindividual variability in systemic and hepatic exposure to these drugs in the clinic.


Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to several translation factors.
Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation initiation. Its N-terminal domain functions as a GTPase-activator protein (GAP) for GTP bound to eIF2, while its C-terminal region nucleates the interactions between multiple translation factors, including eIF1, which acts to inhibit GTP hydrolysis or P(i) release, and the beta subunit of eIF2. These proteins and the events in which they participate are critical for the accurate recognition of the correct start codon during translation initiation. Here, we report the three-dimensional solution structure of the N-terminal domain of human eIF5, comprising two subdomains, both reminiscent of nucleic-acid-binding modules. The N-terminal subdomain contains the "arginine finger" motif that is essential for GAP function but which, unusually, resides in a partially disordered region of the molecule. This implies that a conformational reordering of this portion of eIF5 is likely to occur upon formation of a competent complex for GTP hydrolysis, following the appropriate activation signal. Interestingly, the N-terminal subdomain of eIF5 reveals an alpha/beta fold structurally similar to both the archaeal orthologue of the beta subunit of eIF2 and, unexpectedly, to eIF1. These results reveal a novel protein fold common to several factors involved in related steps of translation initiation. The implications of these observations are discussed in terms of the mechanism of translation initiation.


Benefits and risks of pharmacological treatments for essential tremor.
Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.


The effects of island forest restoration on open habitat specialists: the endangered weevil Hadramphus spinipennis Broun and its host-plant Aciphylla dieffenbachii Kirk.
Human alteration of islands has made restoration a key part of conservation management. As islands are restored to their original state, species interactions change and some populations may be impacted. In this study we examine the coxella weevil, (Hadramphus spinipennis Broun) and its host-plant Dieffenbach's speargrass (Aciphylla dieffenbachii Kirk), which are both open habitat specialists with populations on Mangere and Rangatira Islands, Chathams, New Zealand. Both of these islands were heavily impacted by the introduction of livestock; the majority of the forest was removed and the weevil populations declined due to the palatability of their host-plant to livestock. An intensive reforestation program was established on both islands over 50 years ago but the potential impacts of this restoration project on the already endangered H. spinipennis are poorly understood. We combined genetic and population data from 1995 and 2010-2011 to determine the health and status of these species on both islands. There was some genetic variation between the weevil populations on each island but little variation within the species as a whole. The interactions between the weevil and its host-plant populations appear to remain intact on Mangere, despite forest regeneration. A decline in weevils and host-plant on Rangatira does not appear to be caused by canopy regrowth. We recommend that (1) these populations be monitored for ongoing effects of long-term reforestation, (2) the cause of the decline on Rangatira be investigated, and (3) the two populations of weevils be conserved as separate evolutionarily significant units.


Remote sensing-based predictors improve distribution models of rare, early successional and broadleaf tree species in Utah.
Compared to bioclimatic variables, remote sensing predictors are rarely used for predictive species modelling. When used, the predictors represent typically habitat classifications or filters rather than gradual spectral, surface or biophysical properties. Consequently, the full potential of remotely sensed predictors for modelling the spatial distribution of species remains unexplored. Here we analysed the partial contributions of remotely sensed and climatic predictor sets to explain and predict the distribution of 19 tree species in Utah. We also tested how these partial contributions were related to characteristics such as successional types or species traits.We developed two spatial predictor sets of remotely sensed and topo-climatic variables to explain the distribution of tree species. We used variation partitioning techniques applied to generalized linear models to explore the combined and partial predictive powers of the two predictor sets. Non-parametric tests were used to explore the relationships between the partial model contributions of both predictor sets and species characteristics.More than 60% of the variation explained by the models represented contributions by one of the two partial predictor sets alone, with topo-climatic variables outperforming the remotely sensed predictors. However, the partial models derived from only remotely sensed predictors still provided high model accuracies, indicating a significant correlation between climate and remote sensing variables. The overall accuracy of the models was high, but small sample sizes had a strong effect on cross-validated accuracies for rare species.Models of early successional and broadleaf species benefited significantly more from adding remotely sensed predictors than did late seral and needleleaf species. The core-satellite species types differed significantly with respect to overall model accuracies. Models of satellite and urban species, both with low prevalence, benefited more from use of remotely sensed predictors than did the more frequent core species.Synthesis and applications. If carefully prepared, remotely sensed variables are useful additional predictors for the spatial distribution of trees. Major improvements resulted for deciduous, early successional, satellite and rare species. The ability to improve model accuracy for species having markedly different life history strategies is a crucial step for assessing effects of global change.


Tunable Anion Exchange Membrane Conductivity and Permselectivity via Non-Covalent, Hydrogen Bond Cross-Linking.
Ion exchange membranes (IEMs) are a key component of electrochemical processes that purify water, generate clean energy, and treat waste. Most conventional polymer IEMs are covalently cross-linked, which results in a challenging tradeoff relationship between two desirable properties─high permselectivity and high conductivity─in which one property cannot be changed without negatively affecting the other. In an attempt to overcome this limitation, in this work we synthesized a series of anion exchange membranes containing non-covalent cross-links formed by a hydrogen bond donor (methacrylic acid) and a hydrogen bond acceptor (dimethylacrylamide). We show that these monomers act synergistically to improve both membrane permselectivity and conductivity relative to a control membrane without non-covalent cross-links. Furthermore, we show that the hydrogen bond donor and acceptor loading can be used to tune permselectivity and conductivity relatively independently of one another, escaping the tradeoff observed in conventional membranes.


Stress and pain associated with dressing change in patients with chronic wounds.
To assess pain and stress experienced by patients with chronic wounds at dressing change and to examine how this may be related to long-term chronic stress. The study recruited 43 outpatients, with a mean age of 71.7 ± 14.6 years. The sample included 18 male (42%) and 25 female (58%) patients from Wrexham and Salford (UK), all with chronic wounds that required frequent dressing changes. Physiological and psychological measurements of pain and stress, including numerical ratings (for stress and pain), heart rate, blood pressure, respiration rate, and a questionnaire survey of state and trait anxiety and of chronic stress were recorded at dressing change and in a control condition (at least 24 hours before/after dressing change during a period of rest). Mean heart rate measurements were significantly higher at dressing change, while there was also a trend for higher numerical pain ratings, numerical stress ratings and state anxiety scores at this time. A significant, positive relationship was found between chronic stress and acute episodes of stress experienced at dressing change. Similarly, although not significant, a positive relationship was observed between chronic stress and acute pain reported at dressing change. This study provides a basis for understanding how increased acute pain and stress at dressing change may be related to chronic stress, which has been shown in the literature to contribute to delayed wound healing. The impact of these implications on cost of care and quality of life are also discussed. This study was commissioned by Mölnlycke Health Care Ltd. None of the authors work for Mölnlycke Health Care or have any financial interests with the company. There are no additional conflicts of interest to declare.


Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB.
Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes cells to apoptosis, and functions as a transcriptional repressor. We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-kappaB, including cIAP2, in human tumor cell lines. Daxx interacts with RelB and inhibits RelB-mediated transcriptional activation of the human cIAP2 gene promoter. Daxx also forms complexes with RelB while bound to its target sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays and chromatin immunoprecipitation experiments. Using cells from daxx-/- mouse embryos, we observed that levels of the corresponding murine c-IAP mRNA and protein are increased in cells lacking Daxx. Conversely, c-IAP mRNA and protein levels were reduced in relB-/- cells. Taken together, these observations provide a mechanism that links two previously ascribed functions of Daxx: transcriptional repression and sensitization to apoptosis.


Development and implementation of an introductory endovascular training course for medical students.
Endovascular simulation has been promoted as an educational tool for trainees to practice procedures in a safe environment and improve basic technical skills. We sought to determine whether an established endovascular training course for medical students could increase technical proficiency, enhance interest in vascular surgery, and be implemented at another academic institution. At Center A, medical students participated in an eight-week elective course with a structured curriculum comprised of weekly mentored simulator sessions and didactic teachings. A similar course was developed at Center B to train a similar cohort of students using the same high-fidelity simulator. Demographics and survey data, including interest in vascular surgery, were obtained, and pre- and postcourse graded simulator sessions on renal stent or iliac/superficial femoral artery stent modules were conducted. Performance was assessed by expert observers using a standardized global endovascular rating scale and objective procedural metrics collected from the simulator. Seventy-seven medical students (41 at Center A and 36 at Center B; 56 men and 21 women) completed the course from 2007 to 2009. Parameters measured on the standardized global endovascular rating scale, including angiography skills, wire handling, and interventional criteria as well as simulator-generated metrics, significantly improved from pre- to postcourse values for both groups of medical students at the two institutions (p < 0.05). More than 94% of the students agreed or strongly agreed that the simulation course increased their interest in vascular surgery. A simulation-based endovascular course provides an educational tool that improves basic technical performance and increases interest in vascular surgery among medical students. This simple educational module appears to be transferable and adaptable at another institution with minimal modification to produce similar results.


Why not the University of New Orleans? Social disorganization and sexual violence among internally displaced women of Hurricane Katrina.
Researchers have reported that natural disasters lead to an increase in sexual violence against women and this is echoed by the current situation in Haiti. This is a social pattern throughout the world during periods of war, as well as natural disasters such as tsunamis, famine, and hurricanes. This article examines the prevalence of sexual violence experienced by women students at the University of New Orleans (UNO) before and after Hurricane Katrina using the CORE Alcohol and Drug Survey. Two hundred and thirty seven women participated in the pre-Katrina study and 215 women participated in the post-Katrina study. We hypothesized that, due to the trauma of this disaster, there would be a higher prevalence of sexual aggression against women after Katrina than there was before Katrina. Our analyses yielded no significant differences in any of the measures of sexual violence toward women (nine CORE survey items) pre to post Katrina, so our hypothesis was not supported. We suggest that social organization and cultural attenuation--often indicators of sexual assault in FEMA Greenfield communities--were mitigated by social cohesion found on the UNO campus post-Katrina.


Working conditions and weight gain: a 28-year follow-up study of industrial employees.
Longitudinal studies observing working conditions and weight gain are rare. We aimed to study whether weight gain can be predicted by working conditions or changes in them in a 28-year follow-up. The study population consisted of working-aged industrial employees (n = 449). Data on height and weight were collected in clinical examinations in 1973, 1983 and 2001, and information on working conditions by questionnaires. We analysed the impact of changes in physical strain, temporal requirements and indicators of mental strain at work in 1973 and 1983 on weight changes using analysis of variance, logistic regression analysis and linear mixed longitudinal growth model. The latter was done to account for individual variation in temporal weight change over the study period. Weight gain was prominent in the data and about a third of the participants gained at least 15 kg by the final survey. Changes in physical strain and temporal requirements including working overtime hours among men, and experiencing increased working pace among women, were associated with greater mean weight gain and major weight gain. Job efforts and increasing mental strain showed weak associations with weight gain in men. Changes in the physical strain and temporal requirements seem to predict weight gain but working conditions were in general mostly weakly associated with weight gain in this cohort of initially young adults. The results highlight the importance of stable working hours and reasonable workload on healthy weight.


Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve.
Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve.


Testing the Integral Model of treatment motivation in outpatients with severe mental illness.
The current study tested the Integral Model of treatment motivation (IM) in a sample of 294 outpatients with severe mental illness, using structural equation modelling. The obtained structural model was not consistent with original theory, nor was the model invariant across time and patient groups (psychotic disorders and personality disorders). The patient's perceived suitability of treatment, perceived costs of treatment and outcome expectancy were most strongly associated with motivation and treatment engagement. The model explained between 22 and 86% of variance in clinical outcomes, depending on the timing of the assessment. Currently, the IM does not constitute a robust framework for patterns through which patients become motivated to engage in treatment, but does explain substantial amounts of variance in clinical outcomes. The future potential of IM as a basis for interventions in the mental health care is discussed, including suggestions for subsequent research and potential alterations of the IM to improve its utility for application in clinical practice.


Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.
Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC) has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan-Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.


Reverting the mode of action of the mitochondrial FOF1-ATPase by Legionella pneumophila preserves its replication niche.
Legionella pneumophila, the causative agent of Legionnaires' disease, a severe pneumonia, injects via a type 4 secretion system (T4SS) more than 300 proteins into macrophages, its main host cell in humans. Certain of these proteins are implicated in reprogramming the metabolism of infected cells by reducing mitochondrial oxidative phosphorylation (OXPHOS) early after infection. Here. we show that despite reduced OXPHOS, the mitochondrial membrane potential (Δψm) is maintained during infection of primary human monocyte-derived macrophages (hMDMs). We reveal that L. pneumophila reverses the ATP-synthase activity of the mitochondrial FOF1-ATPase to ATP-hydrolase activity in a T4SS-dependent manner, which leads to a conservation of the Δψm, preserves mitochondrial polarization, and prevents macrophage cell death. Analyses of T4SS effectors known to target mitochondrial functions revealed that LpSpl is partially involved in conserving the Δψm, but not LncP and MitF. The inhibition of the L. pneumophila-induced 'reverse mode' of the FOF1-ATPase collapsed the Δψm and caused cell death in infected cells. Single-cell analyses suggested that bacterial replication occurs preferentially in hMDMs that conserved the Δψm and showed delayed cell death. This direct manipulation of the mode of activity of the FOF1-ATPase is a newly identified feature of L. pneumophila allowing to delay host cell death and thereby to preserve the bacterial replication niche during infection.


Identification and retrospective validation of T-cell epitopes in the hepatitis C virus genotype 4 proteome: an accelerated approach toward epitope-driven vaccine development.
With over 150 million people chronically infected worldwide and millions more infected annually, hepatitis C continues to pose a burden on the global healthcare system. The standard therapy of hepatitis C remains expensive, with severe associated side effects and inconsistent cure rates. Vaccine development against the hepatitis C virus has been hampered by practical and biological challenges posed by viral evasion mechanisms. Despite these challenges, HCV vaccine research has presented a number of candidate vaccines that progressed to phase II trials. However, those efforts focused mainly on HCV genotypes 1 and 2 as vaccine targets and barely enough attention was given to genotype 4, the variant most prevalent in the Middle East and central Africa. We describe herein the in silico identification of highly conserved and immunogenic T-cell epitopes from the HCV genotype 4 proteome, using the iVAX immunoinformatics toolkit, as targets for an epitope-driven vaccine. We also describe a fast and inexpensive approach for results validation using the empirical data on the Immune Epitope Database (IEDB) as a reference. Our analysis identified 90 HLA class I epitopes of which 20 were found to be novel and 19 more had their binding predictions retrospectively validated; empirical data for the remaining 51 epitopes was insufficient to validate their binding predictions. Our analysis also identified 14 HLA class II epitopes, of which 8 had most of their binding predictions validated. Further investigation is required regarding the efficacy of the identified epitopes as vaccine targets in populations where HCV genotype 4 is most prevalent.


Comparative susceptibility of five species of Toxorhynchites mosquitoes to parenteral infection with dengue and other flaviviruses.
Five species of colonized Toxorhynchites mosquitoes were compared for relative susceptibility to parenteral infection with the four dengue serotypes and St. Louis and Japanese encephalitis viruses. Tx. amboinensis, Tx. brevipalpis, Tx. rutilus, and Tx. splendens were equally susceptible to infection with the dengue viruses, while Tx. theobaldi was relatively resistant to infection with those viruses. All five mosquito species were equally susceptible to infection with the encephalitis viruses. The intensity of immunofluorescence in head squashes was slightly less in Tx. brevipalpis infected with the dengue viruses as compared to the other three mosquito species susceptible to those viruses. Immunofluorescence was also less in Tx. theobaldi infected with the encephalitis viruses as compared with all the other mosquito species.


Further Evidence of Morbidity and Dysfunction Associated With Subsyndromal ADHD in Clinically Referred Children.
While the diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) have evolved over the years, some children with impairing ADHD symptoms fail to meet the full diagnostic threshold for the disorder. The main aim of this study was to evaluate the morbidity and dysfunction of subsyndromal ADHD in the clinical setting. Subthreshold and full ADHD subjects were derived from consecutive referrals (n = 2,947) to a pediatric psychopharmacology program at a major academic center. Subjects were diagnosed with subthreshold ADHD if they met at least 1 of the following criteria: (1) their age at onset for ADHD was ≥ 7 years; (2) they had ≥ 5 but < 8 ADHD symptoms using the DSM-III-R or ≥ 4 but < 6 ADHD inattentive or hyperactive/impulsive symptoms using the DSM-IV. Healthy controls were derived from 2 identically designed longitudinal case-control studies of youth with and without ADHD. Psychiatric assessments relied on clinical structured interviews and measures of psychopathology, social functioning, cognitive ability, and academic achievement. Of the 1,931 children diagnosed with ADHD, 140 (7%) were diagnosed with subthreshold ADHD. 48% of subthreshold ADHD subjects had an age at onset ≥ 7 years, and 73% had insufficient symptoms. Reanalysis of findings using DSM-5 criteria showed that only 21% of our subthreshold ADHD subjects would have met DSM-5 criteria based on age at onset of < 12 years, while 79% would have maintained their subthreshold diagnoses. Subjects with subthreshold ADHD differed from controls in the mean number of comorbid disorders; rates of mood, anxiety, and elimination disorders (all P < .001) and substance use disorders (P < .05); scores on all Child Behavior Checklist clinical and social functioning scales; scores on 7 of the 10 Social Adjustment Inventory for Children and Adolescents scales; rates of requiring extra help in school and being placed in a special class; and scores on 4 of the 5 Wechsler Intelligence Scale for Children-Revised Version subscales (excluding Digit Span) as well as in Freedom from Distractibility Index score (P < .001). Subthreshold and full ADHD subjects had similarly elevated Global Assessment of Functioning scores versus controls (P < .001), but subjects with subthreshold ADHD had fewer perinatal complications and better family functioning scores and were more likely to be female and older and to come from families of higher socioeconomic status than subjects with full ADHD. Clinically referred children failing to meet full-threshold diagnosis for ADHD due to either insufficient symptoms or later age at onset have patterns of clinical features highly similar to those with the full syndrome. These results extend to previously reported findings in nonreferred samples documenting the high morbidity and disability associated with subthreshold ADHD.


Mcconnell's patellar taping does not alter knee and hip muscle activation differences during proprioceptive exercises: A randomized placebo-controlled trial in women with patellofemoral pain syndrome.
The purpose of this study was to assess the effect of patellar taping on muscle activation of the knee and hip muscles in women with Patellofemoral Pain Syndrome during five proprioceptive exercises. Forty sedentary women with syndrome were randomly allocated in two groups: Patellar Taping (based in McConnell) and Placebo (vertical taping on patella without any stretching of lateral structures of the knee). Volunteers performed five proprioceptive exercises randomly: Swing apparatus, Mini-trampoline, Bosu balance ball, Anteroposterior sway on a rectangular board and Mediolateral sway on a rectangular board. All exercises were performed in one-leg stance position with injured knee at flexion of 30° during 15s. Muscle activation was measured by surface electromyography across Vastus Medialis, Vastus Lateralis and Gluteus medius muscles. Maximal voluntary contraction was performed for both hip and knee muscles in order to normalize electromyography signal relative to maximum effort during the exercises. ANOVA results reported no significant interaction (P>0.05) and no significant differences (P>0.05) between groups and intervention effects in all exercise conditions. Significant differences (P<0.01) were only reported between muscles, where hip presented higher activity than knee muscles. Patellar taping is not better than placebo for changes in the muscular activity of both hip and knee muscles during proprioceptive exercises. ClinicalTrials.gov NCT02322515.


Design techniques and analysis of high-resolution neural recording systems targeting epilepsy focus localization.
The design of a high-density neural recording system targeting epilepsy monitoring is presented. Circuit challenges and techniques are discussed to optimize the amplifier topology and the included OTA. A new platform supporting active recording devices targeting wireless and high-resolution focus localization in epilepsy diagnosis is also proposed. The post-layout simulation results of an amplifier dedicated to this application are presented. The amplifier is designed in a UMC 0.18µm CMOS technology, has an NEF of 2.19 and occupies a silicon area of 0.038 mm(2), while consuming 5.8 µW from a 1.8-V supply.


A further discussion on revisiting the classification of household composition among elderly people.
This discussion is a reaction to the DeVos article on the classification of households also in the current issue of Journal of Cross-Cultural Gerontology. The need for cross-national and comparative gerontological research is growing. Household composition is a compelling subject for such research, but there is a concurrent increase in the need for flexible and valid classification schemes. The DeVos classification represents an excellent step toward understanding households on a global level. Additional considerations not covered by DeVos include the gender of the coresident child, pseudo-coresidence, and living with grandchildren. These additional issues may complicate classification and, in the end, it is up to the individual researcher to choose schemes based on research questions, guiding theory, and available data. Yer, having a standard as a starting point reduces the complexity of the task of defining a classification scheme to be used comparatively across societies.


[Surgical treatment of liver hydatidosis: our experience with diagnostic and therapeutic consideration].
The Authors report on their experience in diagnosis and treatment of liver hydatidosis (LH). From January 2000 to December 2003, we observed 24 patients (10 male = 42% and 14 female = 58%, male/female ratio 1:1.4, range of age 23 - 80 years, mean age 45.25 years). The most frequent initial symptom was hepigastric and hypocondriac pain (82.6%), meanwhile acute abdominal pain was only in 26.1%. In one half of cases performed radical surgery (total pericistectomy), in 35% of cases the AA subtotal pericistectomy and only in 17% the AA partial pericistectomy. Only one left hepatectomy during total pericistectomy we performed. Major complications were registered, except a post-operative bleeding treated with 3 blood transfusion. The mean time of bedridden was 68 days (range 4 - 35, mode 7 days, median 7 days). All patients are actually in clinical, instrumental and serological follow-up as outpatients (3 months - 2 years): we not encountered any relapse. The surgical treatment of liver hydatidosis must to be radical (as in total pericistectomy), free from severe and disabling complications and without risks and relapses. The choice of type of surgery (radical or conservative) must came from attempt examination of anatomo-clinical tools and experience and agreement of surgical team.


Canine bone shape analysis by use of a radiographic image-classification system.
A radiographic image-classification system was developed to analyze and compare the shape of the humerus of neonatal Labrador Retriever and Labrador Retriever x Beagle pups that were either phenotypically normal or affected with an ocular-skeletal dysplasia syndrome. The system consistently defined the shape of the humerus within the groups of pups studied and indicated a difference in the shape of the humerus between normal and affected pups. Results indicated that the radiographic image-classification system may be able to identify Labrador Retriever pups affected by the ocular-skeletal dysplasia syndrome at or shortly after birth.


Low back pain patients' beliefs about effective/ineffective constituents of a counseling intervention: a follow-up interview study.
Everyday activities are important factors for avoiding the development of chronic low back pain (LBP). The purpose this study was to explore LBP patients' perspective on long-term effects of participating in a counseling intervention designed to motivate them to change work routines and to exercise. Follow-up qualitative study. Semi-structured interviews were made of 25 LBP patients who had received the counseling intervention. Interviews were transcribed and explored with an interpretative thematic analysis. The findings were organized around Kleinman's conception of "explanatory models". For the individual participant the beliefs about the illness were internally coherent, but most often they were idiosyncratic and fitted to the particular participants' overall explanatory model. Participation in the counseling intervention had created a sense of certainty and potential control over the disease and had legitimized their sick role at work and at home. The majority of the patients reported having integrated exercise into their explanatory models and understood exercise to be beneficial in their continual and concrete management of their LBP. The intervention had affected the patients' personal agency and space for action. We suggest that this effect was linked to the individually tailored approach drawing on both educational and motivational agents. Maintaining everyday activities, including retaining one's occupation, is an important factor in low back pain rehabilitation. Counselling on low back pain rehabilitation must be aligned with people's beliefs about their illness. A counselling intervention made patients adopt exercising into their long-term management of low back pain.


New approaches for reconstructing phylogenies from gene order data.
We report on new techniques we have developed for reconstructing phylogenies on whole genomes. Our mathematical techniques include new polynomial-time methods for bounding the inversion length of a candidate tree and new polynomial-time methods for estimating genomic distances which greatly improve the accuracy of neighbor-joining analyses. We demonstrate the power of these techniques through an extensive performance study based on simulating genome evolution under a wide range of model conditions. Combining these new tools with standard approaches (fast reconstruction with neighbor-joining, exploration of all possible refinements of strict consensus trees, etc.) has allowed us to analyze datasets that were previously considered computationally impractical. In particular, we have conducted a complete phylogenetic analysis of a subset of the Campanulaceae family, confirming various conjectures about the relationships among members of the subset and about the principal mechanism of evolution for their chloroplast genome. We give representative results of the extensive experimentation we conducted on both real and simulated datasets in order to validate and characterize our approaches. We find that our techniques provide very accurate reconstructions of the true tree topology even when the data are generated by processes that include a significant fraction of transpositions and when the data are close to saturation.


Feature Selection Based on the SVM Weight Vector for Classification of Dementia.
Computer-aided diagnosis of dementia using a support vector machine (SVM) can be improved with feature selection. The relevance of individual features can be quantified from the SVM weights as a significance map (p-map). Although these p-maps previously showed clusters of relevant voxels in dementia-related brain regions, they have not yet been used for feature selection. Therefore, we introduce two novel feature selection methods based on p-maps using a direct approach (filter) and an iterative approach (wrapper). To evaluate these p-map feature selection methods, we compared them with methods based on the SVM weight vector directly, t-statistics, and expert knowledge. We used MRI data from the Alzheimer's disease neuroimaging initiative classifying Alzheimer's disease (AD) patients, mild cognitive impairment (MCI) patients who converted to AD (MCIc), MCI patients who did not convert to AD (MCInc), and cognitively normal controls (CN). Features for each voxel were derived from gray matter morphometry. Feature selection based on the SVM weights gave better results than t-statistics and expert knowledge. The p-map methods performed slightly better than those using the weight vector. The wrapper method scored better than the filter method. Recursive feature elimination based on the p-map improved most for AD-CN: the area under the receiver-operating-characteristic curve (AUC) significantly increased from 90.3% without feature selection to 92.0% when selecting 1.5%-3% of the features. This feature selection method also improved the other classifications: AD-MCI 0.1% improvement in AUC (not significant), MCI-CN 0.7%, and MCIc-MCInc 0.1% (not significant). Although the performance improvement due to feature selection was limited, the methods based on the p-map generally had the best performance, and were therefore better in estimating the relevance of individual features.