[Fishery of oceanic and coastal sharks in Colima, Jalisco and Michoacán].
Shark fishery is one of the most important activities in the Mexican Pacific coast, nevertheless, there is few data available about the specific captures done by the fleet along the coast. This study describes fishery biology aspects of the shark species catched by the semi-industrial long-line fleet of Manzanillo. Monthly samplings were made on board of these vessels during an annual period from April 2006 to April 2007. Captured species composition (n = 1 962 organisms) was represented by nine species. The one that sustains this fishery was Carcharhinus falciformis (88.12%), followed by Prionace glauca (8.21%). Low frequency species were represented by Sphyrna zygaena (1.78%), Alopias pelagicus (0.82%), Carcharhinus longimanus (0.45%). Furthermore, rare species were Alopias superciliosus (0.35%), Carcharhinus leucas (0.1%), Carcharhinus limbatus (0.1%) and Isurus oxyrinchus (0.05%). Fishery activity affected principally (60-92.70%) young males of C. falciformis, S. zygaena, C. longimanus and I. oxyrinchus; adult males (56-75%) of A. pelagicus, A. superciliosus, and C. limbatus; for P. glauca there were primarily female adults. For all the species found, females showed the bigger sizes when compared to males (with the exception of S. zygaena, that showed sexual dimorphism). Considering the lineal regressions made between precaudal length and total length, and, fork length and total length for C. falciformis, P. glauca, S. zygaena and A. pelagicus, the determination coefficients (r2) showed that both lengths can be useful to obtain the total length of fish with some damage or absence of its caudal fin. The estimated fecundity for C. falciformis was of 3-7 offspring/female of 30-45 cm LT (average of 40.57 +/- 2.03 cm LT); and for P. glauca 5-52 offspring/female of 5-18.6 cm LT (average of 11.61 +/- 0.21 cm LT). In the case of C. longimanus only one female was captured with a total of eight embryos, with an average of 45 cm LT each; for this reason we assumed that the fishery areas do not coincide with the nursery oness for this species. According to the information obtained, we concluded that C. falciformis has a concurrent cycle and P. glauca a consecutive biannual one.


Plaque-like cutaneous mucinosis: case report and literature review.
Midline mucinosis was observed in a 14-year-old man, which was confined to the midline of the back and appeared as asymptomatic, nonindurated, hyperpigmented plaques. Skin biopsies showed prominent interstitial mucinosis with perivascular lymphocytic infiltration. A literature review of plaque-like mucinosis revealed 14 previous cases with this distinct presentation that may overlap with reticular erythematous mucinosis and connective tissue disease. Midline mucinosis has been previously reported in prepubertal children but is rare.


Predicting 7-day survival using heart rate variability in hospice patients with non-lung cancers.
A simple and accurate survival prediction tool can facilitate decision making processes for hospice patients with advanced cancers. The objectives of this study were to explore the association of cardiac autonomic functions and survival in patients with advanced cancer and to evaluate the prognostic value of heart rate variability (HRV) in 7-day survival prediction. A prospective study was conducted on 138 patients with advanced cancer recruited from the hospice ward of a regional hospital in southern Taiwan. Information on functional status and symptom burden of the patients was recorded. Frequency-domain HRV was obtained for the evaluation of cardiac autonomic functions at admission. The end point of the study was defined as the survival status at day 7 after admission to the hospice ward. Multivariate logistic regression analyses were performed to evaluate the independent associations between HRV indices and survival of 7 days or less. The median survival time of the patients was 20 days (95% CI, 17-28 days). Results from the multivariate logistic regression analysis indicated that the natural logarithm-transformed high-frequency power (lnHFP) of a value less than 2 (OR = 3.8, p = 0.008) and ECOG performance status of 3 or 4 (OR = 3.4, p = 0.023) were significantly associated with a higher risk of survival of 7 days or less. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve was 0.71 (95% CI, 0.61-0.81). In hospice patients with non-lung cancers, an lnHPF value below 2 at hospice admission was significantly associated with survival of 7 days or less. HRV might be used as a non-invasive and objective tool to facilitate medical decision making by improving the accuracy in survival prediction.


Types of Inner Dialogues and Functions of Self-Talk: Comparisons and Implications.
Intrapersonal communication occurs in several modes including inner dialogue and self-talk. The Dialogical Self Theory (Hermans, 1996) postulates a polyphonic self that is comprised of a multiplicity of inner voices. Internal dialogical activity implies an exchange of thoughts or ideas between at least two so-called "I-positions" representing specific points of view. Among the functions served by self-talk are self-criticism, self-reinforcement, self-management, and social assessment (Brinthaupt et al., 2009). This paper explores the relationships among different types of internal dialogues and self-talk functions. Participants included college students from Poland (n = 181) and the United States (n = 119) who completed two multidimensional measures of inner dialogue and self-talk. Results indicated moderately strong relationships between inner dialogue types and self-talk functions, suggesting that there is a significant overlap between the two modes of communication. We discuss several implications of these findings for exploring similarities and differences among varieties of intrapersonal communication.


Depressive Symptoms and Resilience among Hispanic Emerging Adults: Examining the Moderating Effects of Mindfulness, Distress Tolerance, Emotion Regulation, Family Cohesion, and Social Support.
Emerging adulthood has been described as a difficult stage in life and may be particularly stressful for Hispanic emerging adults who are disproportionately exposed to adversity and chronic sociocultural stressors. To better prevent and treat depressive disorders among Hispanic emerging adults, more research is needed to identify and understand modifiable determinants that can help this population enhance their capacity to offset and recover from adversity and sociocultural stressors. As such, this study aimed to (1) examine the association between resilience and depressive symptoms among Hispanic emerging adults, and (2) examine the extent to which intrapersonal resources (e.g., mindfulness, distress tolerance, emotion regulation strategies) and interpersonal resources (e.g., family cohesion, social support) moderate the association between resilience and depressive symptoms. To examine these aims, 200 Hispanic emerging adults (ages 18-25) from Arizona (n = 99) and Florida (n = 101) completed a cross-sectional survey, and data were analyzed using hierarchical multiple regression and moderation analyses. Findings from the hierarchical multiple regression indicate that higher resilience was associated with lower depressive symptoms. Findings from the moderation analyses indicate that family cohesion, social support, and emotion regulation strategies (e.g., cognitive reappraisal and expressive suppression) functioned as moderators; however, mindfulness and distress tolerance were not significant moderators. Findings from this study add to the limited literature on resilience among Hispanics that have used validated measures of resilience. Furthermore, we advance our understanding of who may benefit most from higher resilience based on levels of intrapersonal and interpersonal resources.


A novel multivariate approach for biomechanical profiling of stair negotiation.
Stair falls, especially during stair descent, are a major problem for older people. Stair fall risk has typically been assessed by quantifying mean differences between subject groups (e.g. older vs. younger individuals) for a number of biomechanical parameters individually indicative of risk, e.g., a reduced foot clearance with respect to the stair edge, which increases the chances of a trip. This approach neglects that individuals within a particular group may also exhibit other concurrent conservative strategies that could reduce the overall risk for a fall, e.g. a decreased variance in foot clearance. The purpose of the present study was to establish a multivariate approach that characterises the overall stepping behaviour of an individual. Twenty-five younger adults (age: 24.5 ± 3.3 y) and 70 older adults (age: 71.1 ± 4.1 y) descended a custom-built instrumented seven-step staircase at their self-selected pace in a step-over-step manner without using the handrails. Measured biomechanical parameters included: 1) Maximal centre of mass angular acceleration, 2) Foot clearance, 3) Proportion of foot length in contact with stair, 4) Required coefficient of friction, 5) Cadence, 6) Variance of these parameters. As a conventional analysis, a one-way ANOVA followed by Bonferroni post-hoc testing was used to identify differences between younger adults, older fallers and non-fallers. To examine differences in overall biomechanical stair descent behaviours between individuals, k-means clustering was used. The conventional grouping approach showed an effect of age and fall history on several single risk factors. The multivariate approach identified four clusters. Three clusters differed from the overall mean by showing both risky and conservative strategies on the biomechanical outcome measures, whereas the fourth cluster did not display any particularly risky or conservative strategies. In contrast to the conventional approach, the multivariate approach showed the stepping behaviours identified did not contain only older adults or previous fallers. This highlights the limited predictive power for stair fall risk of approaches based on single-parameter comparisons between predetermined groups. Establishing the predictive power of the current approach for future stair falls in older people is imperative for its implementation as a falls prevention tool.


Development and Evaluation of the ADHD Cognitions Scale for Adults.
Objective: The clinical literature on ADHD in adults suggests that "overly positive" or optimistic cognitions may contribute to impairment and failure to use self-regulation skills in this population, yet the research literature on this topic is limited. We developed the ADHD Cognitions Scale (ACS), a brief self-report measure of ADHD-related thoughts, and evaluated its psychometric properties. Method: We collected self-report measures, inculding the ACS, from two large community samples (Ns = 262, 304). Results: The measure demonstrated a one-factor solution that replicated in the second sample. Evidence of good internal consistency and also convergent and divergent validity was obtained for both samples. Scores on the ACS correlated with functional impairment, time management problems, and avoidant coping strategies. Conclusion: With additional study, the ACS may be useful to identify and track maladaptive ADHD-related cognitions during cognitive-behavioral treatment, and to further study the role of these thoughts in ADHD-related impairment.


Brushed nasal epithelial cells are a surrogate for bronchial epithelial CFTR studies.
Recent advances in the management of cystic fibrosis (CF) target underlying defects in the CF transmembrane conductance regulator (CFTR) protein, but efficacy analyses remain limited to specific genotype-based subgroups. Patient-derived model systems may therefore aid in expanding access to these drugs. Brushed human nasal epithelial cells (HNEs) are an attractive tissue source, but it remains unclear how faithfully they recapitulate human bronchial epithelial cell (HBE) CFTR activity. We examined this gap using paired, brushed HNE/HBE samples from pediatric CF subjects with a wide variety of CFTR mutations cultured at the air-liquid interface. Growth and structural characteristics for the two cell types were similar, including differentiation into mature respiratory epithelia. In electrophysiologic analysis, no correlation was identified between nasal and bronchial cultures in baseline resistance or epithelial sodium channel (ENaC) activity. Conversely, robust correlation was demonstrated between nasal and bronchial cultures in both stimulated and inhibited CFTR activity. There was close correlation in modulator-induced change in CFTR activity, and CFTR activity in both cell types correlated with in vivo sweat chloride measurements. These data confirm that brushed HNE cell cultures recapitulate the functional CFTR characteristics of HBEs with fidelity and are therefore an appropriate noninvasive HBE surrogate for individualized CFTR analysis.


High arrhythmic risk in antero-septal acute myocardial ischemia is explained by increased transmural reentry occurrence.
Acute myocardial ischemia is a precursor of sudden arrhythmic death. Variability in its manifestation hampers understanding of arrhythmia mechanisms and challenges risk stratification. Our aim is to unravel the mechanisms underlying how size, transmural extent and location of ischemia determine arrhythmia vulnerability and ECG alterations. High performance computing simulations using a human torso/biventricular biophysically-detailed model were conducted to quantify the impact of varying ischemic region properties, including location (LAD/LCX occlusion), transmural/subendocardial ischemia, size, and normal/slow myocardial propagation. ECG biomarkers and vulnerability window for reentry were computed in over 400 simulations for 18 cases evaluated. Two distinct mechanisms explained larger vulnerability to reentry in transmural versus subendocardial ischemia. Macro-reentry around the ischemic region was the primary mechanism increasing arrhythmic risk in transmural versus subendocardial ischemia, for both LAD and LCX occlusion. Transmural micro-reentry at the ischemic border zone explained arrhythmic vulnerability in subendocardial ischemia, especially in LAD occlusion, as reentries were favoured by the ischemic region intersecting the septo-apical region. ST elevation reflected ischemic extent in transmural ischemia for LCX and LAD occlusion but not in subendocardial ischemia (associated with mild ST depression). The technology and results presented can inform safety and efficacy evaluation of anti-arrhythmic therapy in acute myocardial ischemia.


Suicide rate among former Swedish peacekeeping personnel.
Increased suicide rates for military personnel suffering from post-traumatic stress disorders have been reported in various countries. Although it is known that some peacekeepers are exposed to potentially traumatic events and are thus at risk of suffering from post-traumatic stress reactions, only a few studies have examined suicide rates in this group. Therefore, the aim of this study was to investigate the suicide rate among former Swedish peacekeeping personnel. We compared 39,768 former Swedish peacekeepers to the general population in the National General Population Registry and the Cause-of-Death Registry. A lower number of suicides was found among former Swedish peacekeepers than in the general population. In conclusion, Swedish personnel serving in international peace-keeping operations do not show a higher suicide rate than the general population. Unique problems associated with this research area are discussed.


The interplay of received social support and self-regulatory factors in smoking cessation.
In smoking cessation, individual self-regulation and social support have both proven to be useful. However, the roles of self-regulatory processes and social support are mostly examined separately. The present study aims at examining the unique and joint interactive effects of self-regulation as specified in the health action process approach (HAPA) and social support on smoking cessation. The study tested whether social support can compensate for low levels of self-regulation or whether synergistic effects emerge. DESIGN & MEASURES: Around a self-set quit date, 99 smokers completed baseline questionnaires on HAPA-variables, smoking-specific received social support and smoking cessation (continuous abstinence and point prevalence), with a follow-up Cpproximately 29 days after the quitdate. Social support moderated the association between volitional self-efficacy and smoking, as well as coping planning and smoking but not between action planning and smoking. No compensatory effect of social support for lower levels of individual regulation emerged but the combination of high levels of the individual variables and social support was related to successful smoking cessation, indicating a synergistic effect. The results confirm the importance of examining both self-regulation and social factors in smoking cessation. This should be considered when developing future interventions for smoking cessation.


Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.
Recently, the results of some pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of complete remission, and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(9)/L or moderate thrombocytopenia with bleeding symptoms, transfusion > 4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were > or = 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement. Our results show that in de novo RAEB and RAEB-t, treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity.


Tuning Up an Electronic Structure of the Subphthalocyanine Derivatives toward Electron-Transfer Process in Noncovalent Complexes with C60 and C70 Fullerenes: Experimental and Theoretical Studies.
Noncovalent π-π interactions between chloroboron subphthalocyanine (1), 2,3-subnaphthalocyanine (3), 1,4,8,11,15,18-(hexathiophenyl)subphthalocyanine (4), or 4-tert-butylphenoxyboron subphthalocyanine (2) with C60 and C70 fullerenes were studied by UV-vis and steady-state fluorescence spectroscopy, as well as mass (APCI, ESI, and CSI) spectrometry. Mass spectrometry experiments were suggestive of relatively weak interaction energies between compounds 1-4 and fullerenes. The formation of a new weak charge-transfer band in the NIR region was observed in solution only for subphthalocyanine 4 when titrated with C60 and C70 fullerenes. Molecular structures of the subphthalocyanines 2 and 4 as well as cocrystallite of 4 with C60 fullerene (4···C60) were studied using X-ray crystallography. One of the C60 fullerenes in the crystal structure of 4···C60 was found in the concave region between two subphthalocyanine cores, while the other three fullerenes are aligned above individual isoindole fragments of the aromatic subphthalocyanine. The excited-state dynamics in noncovalent assemblies were studied by transient absorption spectroscopy. The time-resolved photophysics data suggest that only electron-rich subphthalocyanine 4 can facilitate an electron-transfer to C60 or C70 fullerenes, while no electron-transfer from the photoexcited receptors 1-3 to fullerenes was observed in UV-vis and transient spectroscopy experiments. DFT calculations using the CAM-B3LYP exchange-correlation functional and the 6-31+G(d) basis set allowed an estimation of interaction energies for the noncovalent 1:1 and 1:2 (fullerene:subphthalocyanine) complexes. Theoretical data suggest that the weak (∼3.5-10.5 kcal/mol) van der Waals-type interaction energies tend to increase with an increase of the electron density at the subphthalocyanine core with compound 4 being the best platform for noncovalent interactions with fullerenes. DFT calculations also indicate that 1:2 (fullerene:subphthalocyanine) noncovalent complexes are more stable than the corresponding 1:1 assemblies.


Susceptibility-induced distortion that varies due to motion: Correction in diffusion MR without acquiring additional data.
Because of their low bandwidth in the phase-encode (PE) direction, the susceptibility-induced off-resonance field causes distortions in echo planar imaging (EPI) images. It is therefore crucial to correct for susceptibility-induced distortions when performing diffusion studies using EPI. The susceptibility-induced field is caused by the object (head) disrupting the field and it is typically assumed that it remains constant within a framework defined by the object, (i.e. it follows the object as it moves in the scanner). However, this is only approximately true. When a non-spherical object rotates around an axis other than that parallel with the magnetic flux (the z-axis) it changes the way it disrupts the field, leading to different distortions. Hence, if using a single field to correct for distortions there will be residual distortions in the volumes where the object orientation is substantially different to that when the field was measured. In this paper we present a post-processing method for estimating the field as it changes with motion during the course of an experiment. It only requires a single measured field and knowledge of the orientation of the subject when that field was acquired. The volume-to-volume changes of the field as a consequence of subject movement are estimated directly from the diffusion data without the need for any additional or special acquisitions. It uses a generative model that predicts how each volume would look predicated on field change and inverts that model to yield an estimate of the field changes. It has been validated on both simulations and experimental data. The results show that we are able to track the field with high accuracy and that we are able to correct the data for the adverse effects of the changing field.


Modelling muscle energy-metabolism in anaerobic muscle.
A mathematical model of anaerobic muscle energy-metabolism was developed to predict pH and the concentrations of nine muscle metabolites over time. Phosphorous-31 Nuclear Magnetic Resonance was used to measure time-course data for some phosphate metabolites and pH in anoxic M. semitendinosus taken from three slaughtered sheep. Muscles were held at 35 degrees C during the experiment. Measurement commenced 25 min post mortem and concluded before rigor mortis. The model was fitted to these data within experimental error, by simultaneously varying model parameter values and initial substrate concentrations. The model was used to simulate the period from death until metabolic activity ceased, in order to predict the different stages of metabolic response to anoxia. The model suggested that alkalinisation would occur in all three muscles in the first few minutes after the onset of anoxia, followed by a steady decline in pH. For two of the muscles this decline continued until rigor, with final pH values of 5.60 and 6.07. For the other muscle, pH reached a low of 5.60 near rigor but then increased to a final value of 5.73. A rise in pH after rigor has been observed but not previously explained in the literature. The modelling results suggest it was caused by the alkalising effect of adenosine monophosphate deamination being greater at low pH than the acidifying effect of inosine monophosphate dephosphorylation.


Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.
A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses.


Efficacy of increased resistant starch consumption in human type 2 diabetes.
Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.


Framingham-based tools to calculate the global risk of coronary heart disease: a systematic review of tools for clinicians.
To examine the features of available Framingham-based risk calculation tools and review their accuracy and feasibility in clinical practice. medline, 1966-April 2003, and the google search engine on the Internet. TOOL AND STUDY SELECTION: We included risk calculation tools that used the Framingham risk equations to generate a global coronary heart disease (CHD) risk. To determine tool accuracy, we reviewed all articles that compared the performance of various Framingham-based risk tools to that of the continuous Framingham risk equations. To determine the feasibility of tool use in clinical practice, we reviewed articles on the availability of the risk factor information required for risk calculation, subjective preference for 1 risk calculator over another, or subjective ease of use. Two reviewers independently reviewed the results of the literature search, all websites, and abstracted all articles for relevant information. Multiple CHD risk calculation tools are available, including risk charts and computerized calculators for personal digital assistants, personal computers, and web-based use. Most are easy to use and available without cost. They require information on age, smoking status, blood pressure, total and HDL cholesterol, and the presence or absence of diabetes. Compared to the full Framingham equations, accuracy for identifying patients at increased risk was generally quite high. Data on the feasibility of tool use was limited. Several easy-to-use tools are available for estimating patients' CHD risk. Use of such tools could facilitate better decision making about interventions for primary prevention of CHD, but further research about their actual effect on clinical practice and patient outcomes is required.


Nine new species of Aleiodes Wesmael reared at Yanayacu Biological Station (Hymenoptera: Braconidae: Rogadinae) in eastern Ecuador.
Nine new species of Aleiodes (Braconidae: Rogadinae) are described and illustrated: A. aclydis, A. albiterminus, A. arbitrium, A. atripileatus, A. capillosus, A. greeneiyi, A. nebulosus, A. speciosus and A. stilpnos. Because of the difficulties in distinguishing Neotropical species that belong to the circumscriptus and gastritor species-groups, a larger species-group combining the two, termed the circumscriptus/gastritor species-group, is created. The new species described in this study belonged to the seriatus, albitibia, gressitti, and circumscnptus/gastritor species-groups, respectively. Aldodes capillosus represents the first Neotropical species belonging to the gressitti species-group. Of the 34 previously described Neotropical species in Aldodes, only 13 have known biologies. The Aleiodes species in this study were reared from the families Geometridae and Noctuidae, two of the most common host families of other Aleiodes species worldwide.


Hospital catering systems and their impact on the sensorial profile of foods provided to older patients in the UK.
Impaired sensorial perception is very common in older people and low sensorial quality of foods is associated with decreased appetite and dietary intake. Hospital undernutrition in older patients could be linked to sensorial quality of hospital food if the quality were low or inappropriate for older people. The aim of this study was to examine changes in the sensorial quality of different foods that occur as a result of the food journey (i.e. freezing, regeneration, etc.) in the most common hospital catering systems in the UK. A trained sensory panel assessed sensorial descriptors of certain foods with and without the hospital food journey as it occurs in the in-house and cook/freeze systems. The results showed effects of the food journey on a small number of sensorial descriptors related to flavour, appearance and mouthfeel. The majority of these effects were due to temperature changes, which caused accumulation of condensation. A daily variation in sensorial descriptors was also detected and in some cases it was greater than the effect of the food journey. This study has shown that changes occur in the sensory quality of meals due to hospital food journeys, however these changes were small and are not expected to substantially contribute to acceptability or have a major role in hospital malnutrition.


Modeling social dimensions of oral health among older adults in urban environments.
In both developed and developing countries, population aging has attained unprecedented levels. Public health strategies to deliver services in community-based settings are key to enhancing the utilization of preventive care and reducing costs for this segment of the population. Motivated by concerns of inadequate access to oral health care by older adults in urban environments, this article presents a portfolio of systems science models that have been developed on the basis of observations from the ElderSmile preventive screening program operated in northern Manhattan, New York City, by the Columbia University College of Dental Medicine. Using the methodology of system dynamics, models are developed to explore how interpersonal relationships influence older adults' participation in oral health promotion. Feedback mechanisms involving word of mouth about preventive screening opportunities are represented in relation to stocks that change continuously via flows, as well as agents whose states of health care utilization change discretely using stochastic transitions. Agent-based implementations illustrate how social networks and geographic information systems are integrated into dynamic models to reflect heterogeneous and proximity-based patterns of communication and participation in the ElderSmile program. The systems science approach builds shared knowledge among an interdisciplinary research team about the dynamics of access to opportunities for oral health promotion. Using "what if" scenarios to model the effects of program enhancements and policy changes, resources may be effectively leveraged to improve access to preventive and treatment services. Furthermore, since oral health and general health are inextricably linked, the integration of services may improve outcomes and lower costs.


Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor.
Liposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading method of bacteriomimetic liposomes for a novel, hydrophobic compound (HIPS5031) inhibiting energy-coupling factor transporters (ECF transporters), an underexplored antimicrobial target. The liposomes were composed of DOPG (18:1 (Δ9-cis) phosphatidylglycerol) and CL (cardiolipin), resembling the cell membrane of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and enriched with cholesterol (Chol). The size and polydispersity of the DOPG/CL/± Chol liposomes remained stable over 8 weeks when stored at 4 °C. Loading of the ECF transporter inhibitor was achieved by thin film hydration and led to a high encapsulation efficiency of 33.19% ± 9.5% into the DOPG/CL/Chol liposomes compared to the phosphatidylcholine liposomes (DMPC/DPPC). Bacterial growth inhibition assays on the model organism Bacillus subtilis revealed liposomal HIPS5031 as superior to the free drug, showing a 3.5-fold reduction in CFU/mL at a concentration of 9.64 µM. Liposomal HIPS5031 was also shown to reduce B. subtilis biofilm. Our findings present an explorative basis for bacteriomimetic liposomes as a strategy against drug-resistant pathogens by surpassing the drug-formulation barriers of innovative, yet unfavorably hydrophobic, antibiotics.


Ablation of AMPK-Related Kinase MPK38/MELK Leads to Male-Specific Obesity in Aged Mature Adult Mice.
Murine protein serine-threonine kinase 38 (MPK38)/maternal embryonic leucine zipper kinase (MELK) is implicated in diverse biological processes, including the cell cycle, apoptosis, and tumorigenesis; however, its physiological role is unknown. Using mice lacking MPK38 (MPK38-/-), we found that MPK38-/- male, but not female, mice (7 months of age) became obese while consuming a standard diet, displayed impairments in metabolism and inflammation, became more obese than wild-type mice while consuming a high-fat diet, and exhibited no castration/testosterone replacement-induced metabolic changes. The adenoviral restoration of MPK38 ameliorated the obesity-induced adverse metabolic profile of the obese male, but not female, mice. Seven-month-old MPK38-/- males displayed typical postcastration concentrations of serum testosterone with an accompanying decrease in serum luteinizing hormone (LH) levels, suggesting a role for MPK38 in the age-related changes in serum testosterone in aged mature adult male mice. The stability and activity of MPK38 were increased by dihydrotestosterone but reduced by estradiol (E2). These findings suggest MPK38 as a therapeutic target for obesity-related metabolic disorders in males.


Investigation of associations between exposures to pesticides and testosterone levels in Thai farmers.
We conducted a cross-sectional study to assess the relationship between pesticide exposures and testosterone levels in 133 male Thai farmers. Urine and serum samples were collected concurrently from participants. Urine was analyzed for levels of specific and nonspecific metabolites of organophosphates (OPs), pyrethroids, select herbicides, and fungicides. Serum was analyzed for total and free testosterone. Linear regression analyses revealed significant negative relationships between total testosterone and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) after controlling for covariates (eg, age, BMI, smoking status). Positive significant associations were found between some OP pesticides and total testosterone. Due to the small sample size and the observational nature of the study, future investigation is needed to confirm our results and to elucidate the biological mechanisms.


Improving preventive care by prompting physicians.
To assess the impact of prompting physicians on health maintenance, answer questions regarding the mode of delivery, and identify opportunities and limitations of this information intervention. Systematic electronic and manual searches (January 1, 1966, to December 31, 1996) were conducted to identify clinical trial reports on prompting clinicians. Three eligibility criteria were applied: (1) randomized controlled clinical trial, (2) clinician prompt, alert, or reminder in the study group and no similar intervention in the control group, and (3) measurement of the intervention effect on the frequency of preventive care procedures. Data were abstracted by independent reviewers using a standardized abstraction form, and quality of methodology was scored. A series of meta-analyses on triggering clinical actions was performed using the random-effects method. The statistical analyses included 33 eligible studies, which involved 1547 clinicians and 54 693 patients. Overall, prompting can significantly increase preventive care performance by 13.1% (95% confidence interval [CI], 10.5%-15.6%). However, the effect ranges from 5.8% (95% CI, 1.5%-10.1%) for Papanicolaou smear to 18.3% (95% CI, 11.6%-25.1%) for influenza vaccination. The effect is not cumulative, and the length of intervention period did not show correlation with effect size (R = -0.015, P = .47). Academic affiliation, ratio of residents, and technique of delivery did not have a significant impact on the clinical effect of prompting. Dependable performance improvement in preventive care can be accomplished through prompting physicians. Vigorous application of this simple and effective information intervention could save thousands of lives annually. Health care organizations could effectively use prompts, alerts, or reminders to provide information to clinicians when patient care decisions are made.


Targeted Metabolomics of Nonhuman Primate Serum after Exposure to Ionizing Radiation: Potential Tools for High-throughput Biodosimetry.
There is a need for research to rapidly determine an individual's absorbed dose and its potential health effects after a potential radiological or nuclear event that could expose large portions of a population to ionizing radiation (IR). Studies on biomarker identification after radiation exposure could aid in biodosimetry, identifying individual dose absorbed, as well as biologic response, and administering immediate and proper medical care. Metabolomics on easily accessible biofluids is an emerging field with potential for high-throughput biodosimetry. While tremendous effort has been put into obtaining discovery based global radiation signatures from a number of biofluids and model organisms, quantitative targeted analysis on a subset of known radiation biomarkers is required to develop an optimized panel of biomarkers for future clinical applications. The current study analyzes levels of several known broad chemical groups (acylcarnitines, amino acids, phosphatidylcholines, and biogenic amines) affected by IR in serum from nonhuman primates (NHP) 7 days after exposure through multiple reaction monitoring (MRM) analysis with a triple quadrupole mass spectrometry (MS) platform. We identified several novel metabolites affected by IR exposure through univariate and unsupervised multivariate analyses. Levels of acylcarnitines, amino acids, and phospholipids were perturbed indicating altered protein metabolism, fatty acid β-oxidation, and inflammation. Fold changes in carnitine and short-chain acylcarnitines (acetylcarnitine, propionylcarnitine, butyrylcarnitine, and valerylcarnitine) complement previous global radiation signatures on NHP; notably, the levels of change were lower than previously observed in urine. Decreased levels of glutamate, citrulline, and arginine after IR are biomarkers indicating gastrointestinal syndrome and perturbations to the urea cycle. Sex differences were also assessed and were more prevalent in circulating acylcarnitines and phospholipids after IR exposure. These biomarkers may be combined with previously described compounds from DNA damage to develop a defined metabolomic biodosimetry panel to be analyzed by MS platforms, which are increasingly available in clinical laboratories.


Uniquely integrated Fe-doped Ni(OH)2 nanosheets for highly efficient oxygen and hydrogen evolution reactions.
Developing high-efficiency electrocatalysts for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is vital for the production of hydrogen on a large scale by electrocatalytic splitting of water. Herein, Fe-doped Ni(OH)2 nanosheets directly grown on commercial Ni foam (FeNiOH/NF) were fabricated through a facile hydrothermal method in (NH4)2S2O8 aqueous solution containing iron salts. The integrated architecture with hierarchical pores is beneficial for exposing sufficient catalytically active sites and providing evaluated structural and electrical properties. In particular, the Fe-induced partial-charge-transfer greatly modifies the electronic structure of Ni(OH)2, which evidently promotes the electrocatalytic activity of the as-fabricated FeNiOH/NF for OER and HER. Thus, as an electrocatalyst for OER, FeNiOH/NF exhibits excellent activity with overpotentials of 271 and 318 mV to deliver current densities of 20 and 100 mA cm-2, respectively, with a small Tafel slope of 72 mV dec-1 in 1.0 M KOH, demonstrating the very high level of novelty and sufficient improvement over the current state-of-the-art IrO2 electrocatalyst. Most importantly, there is an increase in overpotential by only 23 mV during continuous reaction for over 20 h at an applied potential of 1.62 V to deliver current density of 500 mA cm-2. The as-fabricated electrocatalyst also enables high HER activity with robust stability. Finally, an overall water splitting current density of 10 mA cm-2 can be obtained at a cell voltage of 1.67 V in a two-electrode alkaline electrolyzer using FeNiOH/NF as both anode and cathode, along with impressive operation stability. This development with significant over the state-of-the-art IrO2 electrocatalyst can be widely extended to large-scale fabrication of versatile electrocatalysts for efficient water splitting technology.


Treatment and outcomes in necrotising autoimmune myopathy: An Australian perspective.
Necrotising Autoimmune Myopathy (NAM) presents as a subacute proximal myopathy with high creatine kinase levels. It is associated with statin exposure, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody, connective tissue diseases, signal recognition particle (SRP) antibody and malignancy. This case series presents our Western Australian NAM patient cohort: comparing the subgroup presentations, biopsy appearance and treatment outcomes. We retrospectively collected data on patients diagnosed with NAM at the Western Australian Neuroscience Research Institute between the years 2000 and 2015. We identified 20 patients with Necrotising Autoimmune Myopathy: 14 with anti-HMGCR antibodies; two with anti-SRP antibodies; three with connective tissue disease; two as yet unspecified. Median creatine kinase level was 6047units/L (range 1000-17000). The statin naïve patients with HMGCR antibodies and patients with SRP antibodies were the most severely affected subgroups, with higher creatine kinase levels, and were more resistant to immunotherapy. Two or more immunotherapy agents were required in 90%; eight patients required IVIG and rituximab. Steroid weaning commonly precipitated relapses. Four patients had complete remission, and the remaining patients still require immunotherapy. Necrotising Autoimmune Myopathy is a potentially treatable myopathy, which can be precipitated by statin therapy and requires early, aggressive immunotherapy, usually requiring multiple steroid sparing agents for successful steroid weaning.


Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy.
Clinical manifestation and renal histology serve as the current "gold standard" for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal -miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-β1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-β1 was inversely correlated (r = -0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-β and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.


Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans.
Premature ovarian failure (POF) affects up to 1.4% of women under the age of 40 yr and less than 30% of cases have a known cause. Here we describe a new mouse model of POF resulting from oocyte-specific ablation of core 1-derived (mucin) O-glycans and complex and hybrid N-glycans. Females carrying floxed alleles of both the C1galt1 (T-syn) and Mgat1 glycosyltransferase genes and a ZP3Cre transgene, generate oocytes lacking complex O- and N-glycans following oocyte-specific deletion at the primary follicle stage. We previously showed that few double-mutant females are fertile, and those produce only a single small litter. Here we show that ovarian function declined rapidly in double-mutant females with less than 1% ovulating at 11 wk of age after superovulation with exogenous gonadotropins. Ovary weight was significantly decreased in double-mutant females by 3 months of age, consistent with a decrease in the number of developing follicles. FSH levels in double-mutant females were elevated at 3 months of age, and testosterone and inhibin A were decreased, showing that the loss of complex N- and O-glycans from oocyte glycoproteins affected hypothalamic-pituitary-gonadal feedback loops. The absence of developing follicles, ovary dysfunction, reduced testosterone and inhibin A, and elevated FSH in double-mutant females lacking C1galt1 and Mgat1 in oocytes represents a new mouse model for the study of follicular POF.


Possible interbreeding in late Italian Neanderthals? New data from the Mezzena jaw (Monti Lessini, Verona, Italy).
In this article we examine the mandible of Riparo Mezzena a Middle Paleolithic rockshelter in the Monti Lessini (NE Italy, Verona) found in 1957 in association with Charentian Mousterian lithic assemblages. Mitochondrial DNA analysis performed on this jaw and on other cranial fragments found at the same stratigraphic level has led to the identification of the only genetically typed Neanderthal of the Italian peninsula and has confirmed through direct dating that it belongs to a late Neanderthal. Our aim here is to re-evaluate the taxonomic affinities of the Mezzena mandible in a wide comparative framework using both comparative morphology and geometric morphometrics. The comparative sample includes mid-Pleistocene fossils, Neanderthals and anatomically modern humans. This study of the Mezzena jaw shows that the chin region is similar to that of other late Neanderthals which display a much more modern morphology with an incipient mental trigone (e.g. Spy 1, La Ferrassie, Saint-Césaire). In our view, this change in morphology among late Neanderthals supports the hypothesis of anatomical change of late Neanderthals and the hypothesis of a certain degree of interbreeding with AMHs that, as the dating shows, was already present in the European territory. Our observations on the chin of the Mezzena mandible lead us to support a non abrupt phylogenetic transition for this period in Europe.


First Report of a Binucleate Rhizoctonia (AG-A) from Potato Stems Infecting Potatoes and Sugarbeet in the Pacific Northwest.
Rhizoctonia solani causes economically important diseases on potatoes and sugarbeet throughout the world (2). R. solani is a species complex of 13 anastomosis groups (AGs) of which R. solani AG3-PT is most commonly associated with potato and AG2-2 and AG4 with sugarbeet. However, several AGs, including AG2-2 and AG4, have been recorded causing potato diseases (2,3). In summer 2012, plants in potato fields in Idaho were sampled for R. solani. Isolations were attempted from symptomatic plants. DNA extracted from the resulting pure Rhizoctonia cultures was screened using a real-time PCR assay for AG3-PT (3). For the isolates that tested negative for AG3-PT, AG was determined by amplifying and sequencing the rDNA internal transcribed spacer (ITS) region using the primers ITS5 (5'-GGAAGTAAAAGTCGTAACAAGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3'). The resulting sequences of two isolates (isolates 204 and 206, GenBank Accession No. KC782951) shared 99% identity with other AG-A isolates (AY927358 and AY927356). Koch's postulates were confirmed for isolate 206 by placing five 10-mm plugs, from 10-day-old potato dextrose agar (PDA) cultures, onto the surface of a soil-less potting mix (composed of peat moss, perlite, and sand) of 1-liter pots, where non-inoculated PDA plugs served as a control. Each pot contained a 'Rosara' seed tuber or three ungerminated (BETASEED - BTS 27RR10) sugarbeet seeds (n = 5). Pots were incubated in a glasshouse between 18 and 22°C for 1 month and then assessed for disease. For potatoes, a pigmented necrosis was observed at the soil interface in 88% of the stems and plants were stunted relative to the non-inoculated controls. A significant reduction in root growth was observed in 60% of the germinated sugarbeet plants. Control plants of both potatoes and beets were asymptomatic. For reisolation, 1-cm sections were taken from each potato stem and germinated beet plant, surface sterilized, and placed on alkaline water agar. The reisolated fungi were identified using morphology and a subset was confirmed by sequencing. Isolate 206 was successfully recovered from 84% of the potato stems and from 20% of the sugarbeet seedlings. In a similar experiment, 2-month-old potato and sugarbeet plants were inoculated using 50 g of autoclaved barley grains (inoculated with isolate 206) per 1-liter pot. Between 40 and 60% of inoculated plants appeared stunted in both cases. Pigmented necrosis was observed at the soil interface on 45% of the potato stems and reduced root growth was observed in the 50% of the sugarbeet plants. Control plants were asymptomatic. To our knowledge, this is the first report of the binucleate AG-A causing disease in Idaho on potato stems. BNR species have previously been isolated from potato (4) and sugarbeet plants (1). The binucleate Rhizoctonia AG-A caused disease on potato stems and sugarbeet roots and was readily reisolated. Since sugarbeet is commonly grown in rotation with potato in Idaho, such a rotation could increase the risk of soilborne infection to either crop by AG-A. It is known that AGs can differ in fungicide sensitivity (2), and thus a knowledge of which AGs may be present is important when considering disease management strategies. References: (1) C. A. Strausbaugh et al. Can. J. Plant Pathol. 33:210, 2011. (2) L. Tsror. Biology, Epidemiology and Management of Rhizoctonia solani on Potato 158:649, 2010. (3) J. Woodhall et al. Eur. J. Plant Pathol. 136:273, 2013. (4) Y. G. Yang and X. H. Wu. Plant Dis. 97:1246, 2013.


Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells.
Metabolic reprogramming is an important driver of tumor progression; however, the metabolic regulators of tumor cell motility and metastasis are not understood. Here, we show that tumors maintain energy production under nutrient deprivation through the function of HSP90 chaperones compartmentalized in mitochondria. Using cancer cell lines, we found that mitochondrial HSP90 proteins, including tumor necrosis factor receptor-associated protein-1 (TRAP-1), dampen the activation of the nutrient-sensing AMPK and its substrate UNC-51-like kinase (ULK1), preserve cytoskeletal dynamics, and release the cell motility effector focal adhesion kinase (FAK) from inhibition by the autophagy initiator FIP200. In turn, this results in enhanced tumor cell invasion in low nutrients and metastatic dissemination to bone or liver in disease models in mice. Moreover, we found that phosphorylated ULK1 levels were correlated with shortened overall survival in patients with non-small cell lung cancer. These results demonstrate that mitochondrial HSP90 chaperones, including TRAP-1, overcome metabolic stress and promote tumor cell metastasis by limiting the activation of the nutrient sensor AMPK and preventing autophagy.


The Bacillus BioBrick Box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis.
Standardized and well-characterized genetic building blocks are a prerequisite for the convenient and reproducible assembly of novel genetic modules and devices. While numerous standardized parts exist for Escherichia coli, such tools are still missing for the Gram-positive model organism Bacillus subtilis. The goal of this study was to develop and thoroughly evaluate such a genetic toolbox. We developed five BioBrick-compatible integrative B. subtilis vectors by deleting unnecessary parts and removing forbidden restriction sites to allow cloning in BioBrick (RFC10) standard. Three empty backbone vectors with compatible resistance markers and integration sites were generated, allowing the stable chromosomal integration and combination of up to three different devices in one strain. In addition, two integrative reporter vectors, based on the lacZ and luxABCDE cassettes, were BioBrick-adjusted, to enable β-galactosidase and luciferase reporter assays, respectively. Four constitutive and two inducible promoters were thoroughly characterized by quantitative, time-resolved measurements. Together, these promoters cover a range of more than three orders of magnitude in promoter strength, thereby allowing a fine-tuned adjustment of cellular protein amounts. Finally, the Bacillus BioBrick Box also provides five widely used epitope tags (FLAG, His10, cMyc, HA, StrepII), which can be translationally fused N- or C-terminally to any protein of choice. Our genetic toolbox contains three compatible empty integration vectors, two reporter vectors and a set of six promoters, two of them inducible. Furthermore, five different epitope tags offer convenient protein handling and detection. All parts adhere to the BioBrick standard and hence enable standardized work with B. subtilis. We believe that our well-documented and carefully evaluated Bacillus BioBrick Box represents a very useful genetic tool kit, not only for the iGEM competition but any other BioBrick-based project in B. subtilis.


Unemployment, public-sector healthcare expenditure and colorectal cancer mortality in the European Union: 1990-2009.
We examined the association between unemployment and government spending on healthcare with colorectal cancer mortality. Retrospective observational study using data from the World Bank and WHO. Multivariate regression analysis was used, controlling for country-specific differences in infrastructure and demographics. A 1 % increase in unemployment was associated with a significant increase in colorectal cancer mortality in both men and women [men: coefficient (R) = 0.0995, 95 % confidence interval (CI) 0.0132-0.1858, P = 0.024; women: R = 0.0742, 95 % CI 0.0160-0.1324, P = 0.013]. A 1 % increase in government spending on healthcare was associated with a statistically significant decrease in colorectal cancer mortality across both sexes (men: R = -0.4307, 95 % CI -0.6057 to -0.2557, P < 0.001; women: R = -0.2162, 95 % CI -0.3407 to -0.0917, P = 0.001). The largest changes in mortality occurred 3-4 years following changes in either economic variable. Unemployment rises are associated with a significant increase in colorectal cancer mortality, whilst government healthcare spending rises are associated with falling mortality. This is likely due, in part, to reduced access to healthcare services and has major implications for clinicians and policy makers alike.


Soil vs. canopy seed storage and plant species coexistence in species-rich Australian shrublands.
The fire-prone shrublands of southwestern Australia are renowned for their high plant species diversity and prominence of canopy seed storage (serotiny). We compared species richness, abundance, and life history attributes for soil and canopy seed banks in relation to extant vegetation among four sites with different substrate conditions and high species turnover (50-80%) to identify whether this unusual community-level organization of seed storage might contribute to maintenance of high species richness. Soil seed bank (SSB) densities were low to moderate (233-1435 seeds/m2) compared with densities for other Mediterranean-type vegetation and were lowest for sites with highest canopy seed bank (CSB) species richness and lowest nutrient availability, but not richness or abundance of resprouters. Annuals were infrequent in the lowest nutrient sites, but there was no evidence that small SSB size was due to low seed inputs or a trade-off between seed production/storage and seed size in response to low nutrient availability. Sorensen's similarity between SSB and extant vegetation was 26-43% but increased to 54-57% when the CSB was included, representing levels higher than reported for most other ecosystems. Resprouting species were well represented in both the SSB and CSB, and there was no evidence for lower seed production in resprouters than in non-sprouters overall. The SSB and CSB held no species in common and were characterized by markedly different seed dispersal attributes, with winged or small seeds in the CSB and seeds dispersed by ants, birds, and wind (though none with wings) in the SSB. There was no evidence of spatial differentiation in the distribution of seeds of SSB species between vegetated and open microsites that might facilitate species coexistence, but most woody non-sprouters showed aggregation at scales of 1-2 m, implying limited seed dispersal. High similarity between overall seed bank (SSB + CSB) and extant species composition, high number of resprouting species, and seed dispersal processes before (SSB) and after fire (CSB) leading to differential spatial aggregation of post-fire recruits from the two seed bank types may buffer species composition against rapid change and provide a mechanism for maintaining species coexistence at the local scale.


Efficient 3D sensitivity analysis of surface plasmon waveguide structures.
We present a novel analytical approach for efficient sensitivity analysis of surface plasmon polaritons (SPPs) waveguide-based structures using the beam propagation method (BPM). Our approach exploits the adjoint variable technique to extract the response sensitivities with respect to all the design parameters regardless of their number. No extra BPM simulations are required. The accuracy of the results are comparable to those obtained using the expensive central finite difference approximations applied at the response level. Our approach is successfully applied to different SPPs structures for different applications.


Structural change in response to ligand binding.
The minutiae of subtle changes that occur in response to ligand binding in multiprotein complexes are often difficult to assess without resource to high resolution X-ray analysis. Recent developments in mass spectrometry, however, are providing insight into dynamic changes within components. In this article we review recent applications of MS for selection of ligands and definition of their binding characteristics for individual protein targets through to macromolecular complexes such as ribosomes.


Identification of a WSSV neutralizing scFv antibody by phage display technology and in vitro screening.
White spot syndrome virus (WSSV) is one of the most significant viral pathogens causing high mortality and economic damage in shrimp aquaculture. Although intensive efforts were undertaken to detect and characterize WSSV infection in shrimp during the last decade, we still lack methods either to prevent or cure white spot disease. Most of the studies on neutralizing antibodies from sera have been performed using in vivo assays. For the first time, we report use of an in vitro screening method to obtain a neutralizing scFv antibody against WSSV from a previously constructed anti-WSSV single chain fragment variable region (scFv) antibody phage display library. From clones that were positive for WSSV by ELISA, 1 neutralizing scFv antibody was identified using an in vitro screening method based on shrimp primary lymphoid cell cultures. The availability of a neutralizing antibody against the virus should accelerate identification of infection-related genes and the host cell receptor, and may also enable new approaches to the prevention and cure of white spot disease.


The effect of the anastomotic size on gastric emptying after hemigastrectomy with Billroth II reconstruction.
To determine if the size of the gastrojejunal anastomosis after Billroth II reconstruction was the rate-limiting factor in gastric emptying in the postoperative period. Twelve mongrel dogs were randomized to have either 1.5 cm or 5 cm gastrojejunal anastomoses prior to Billroth II hemigastrectomy. Each dog had three solid and three liquid radiolabelled emptying studies pre- and postoperatively. Data were collected using a gamma camera. For liquid studies, images were obtained at 0 min, 2 min, 4 min, 6 min, 8 min, 10 min, 20 min, 30 min, 40 min, 50 min and 60 min. For solid studies, images were obtained at 0 min, 5 min, 10 min, 20 min, 30 min, 40 min, 50 min, 60 min, 70 min, 80 min, 90 min, 100 min, 110 min and 120 min. Means were compared by analysis of variance using the repeated measures option. Postoperative liquid emptying was significantly faster in the first 10 min with both 1.5 cm and 5 cm anastomoses compared with preoperative scans in the same animals (45% versus 20% and 48% versus 29%, respectively). On the other hand, solid gastric emptying was much slower postoperatively with the 1.5 cm anastomosis compared with preoperative scans (29% versus 65%) as well as compared with postoperative 5 cm anastomosis (29% versus 62%) at the end of 120 min. Our model suggests that the gastric emptying of solids is affected by the size of the gastrojejunal anastomosis and not by the diameter of the efferent limb of the small intestine following Billroth II reconstruction.


Reduced coffee consumption among individuals with primary sclerosing cholangitis but not primary biliary cirrhosis.
Coffee consumption has been associated with decreased risk of liver disease and related outcomes. However, coffee drinking has not been investigated among patients with cholestatic autoimmune liver diseases, primary biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). We investigated the relationship between coffee consumption and risk of PBC and PSC in a large North American cohort. Lifetime coffee drinking habits were determined from responses to questionnaires from 606 patients with PBC, 480 with PSC, and 564 healthy volunteers (controls). Patients (those with PBC or PSC) were compared with controls by using the Wilcoxon rank sum test for continuous variables and c(2) method for discrete variables. Logistic regression was used to analyze the estimate of the effects of different coffee parameters (time, frequency, and type of coffee consumption) after adjusting for age, sex, smoking status, and education level. Patients with PBC and controls did not differ in coffee parameters. However, 24% of patients with PSC had never drunk coffee compared with 16% of controls (P < .05), and only 67% were current drinkers compared with 77% of controls (P < .05). Patients with PSC also consumed fewer lifetime cups per month (45 vs 47 for controls, P < .05) and spent a smaller percentage of their lifetime drinking coffee (46.6% vs 66.7% for controls, P < .05). These differences remained significant in a multivariate model. Among PSC patients with concurrent ulcerative colitis, coffee protected against proctocolectomy (hazard ratio, 0.34; P < .001). Coffee consumption is lower among patients with PSC, but not PBC, compared with controls.


Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.
Platelet-derived endothelial cell growth factor (PDECGF) also called thymidine phosphorylaze (TP) has been shown to have considerable angiogenic activity. 141 cases of early stage non-small cell lung cancer were stained for TP and vascular grade using the P-GF.44C and JC70 MoAbs, respectively. The early steps of TP activation could be identified in 27 cases, where one or two foci of cancer cell TP overexpression occurred within a general pattern of negative/weak staining. Thirty-three foci of overexpression were analyzed for the local microvessel density in the adjacent stroma, assessed by microvessel counting (MC) and Chalkley Score (CS) comparatively with the remaining TP negative tumor areas. The degree of local inflammatory (lymphocyte and macrophage) infiltration was also assessed. A statistically significant increase of mean MC and mean CS was observed in areas of TP overexpression in both low and high angiogenesis cases. Overall, the mean MC in overexpressing areas, assessed in 250x fields, was 20.4 +/- 12.8 vs. 13.6 +/- 9.5 in areas with no TP expression (p = 0.0001). The mean CS was 5.7 +/- 3.3 and 4.0 +/- 2.1, respectively (p = 0.0003). Ten out of 19 (54%) cases with low lymphocytic infiltration showed marked stromal lymphocytic infiltration in the area of focal TP overexpression (p = 0.01). The present study provides further evidence of a direct association of TP and the process of angiogenesis in non-small cell lung cancer.


Restricted epitope specificity determined by variable region germline segment pairing in rodent antibody repertoires.
Antibodies from B-cell clonal lineages share sequence and structural properties as well as epitope specificity. Clonally unrelated antibodies can similarly share sequence and specificity properties and are said to be convergent. Convergent antibody responses against several antigens have been described in humans and mice and include different classes of shared sequence features. In particular, some antigens and epitopes can induce convergent responses of clonally unrelated antibodies with restricted heavy (VH) and light (VL) chain variable region germline segment usage without similarity in the heavy chain third complementarity-determining region (CDR H3), a critical specificity determinant. Whether these V germline segment-restricted responses reflect a general epitope specificity restriction of antibodies with shared VH/VL pairing is not known. Here, we investigated this question by determining patterns of antigen binding competition between clonally unrelated antigen-specific rat antibodies from paired-chain deep sequencing datasets selected based solely on VH/VL pairing. We found that antibodies with shared VH/VL germline segment pairings but divergent CDR H3 sequences almost invariably have restricted epitope specificity indicated by shared binding competition patterns. This epitope restriction included 82 of 85 clonally unrelated antibodies with 13 different VH/VL pairings binding in 8 epitope groups in 2 antigens. The corollary that antibodies with shared VH/VL pairing and epitope-restricted binding can accommodate widely divergent CDR H3 sequences was confirmed by in vitro selection of variants of anti-human epidermal growth factor receptor 2 antibodies known to mediate critical antigen interactions through CDR H3. Our results show that restricted epitope specificity determined by VH/VL germline segment pairing is a general property of rodent antigen-specific antibodies.


Simple route to the doubly ortho-palladated azobenzenes: building blocks for organometallic polymers and metallomesogens.
A new class of doubly cyclopalladated complexes, {PdCl(dmf)}2(mu-azb) (1) and {PdCl(dmf)}2(mu-aazb) (2), has been prepared in dimethylformamide (dmf) by reaction of azobenzene (azb) and 4-aminoazobenzene (aazb), respectively, with an excess of PdCl2(CH3CN)2 complex. Recrystallization of 1 and 2 in dimethyl sulfoxide (dmso) yields complexes {PdCl(dmso)}2(mu-azb) (3) and {PdCl(dmso)}2(mu-aazb) (4), respectively. The crystal structures of 1 and 4 have been determined by X-ray diffraction. All complexes are characterized by 1H and 13C NMR spectra and elemental analysis. In both crystal structures, solvent molecules are bound to palladium through oxygen atoms and oriented trans to carbon. In view of greater preference of palladium to nitrogen and sulfur atoms, the experimental structures were rationalized by quantum-chemical calculations and confirmed as the most stable isomers.


Dose-dependent effects of meclofenamate on peripheral vasculature of conscious rabbits.
1. Changes in systemic haemodynamics and organ blood flow were measured in conscious rabbits after various doses of intravenous sodium meclofenamate, an inhibitor of prostaglandin cyclo-oxygenase. 2. Meclofenamate had no effect on arterial pressure or cardiac output but caused a dose-dependent fall in renal blood flow. 3. Meclofenamate also reduced adrenal perfusion but, in contrast, caused a dose-dependent increase in blood flow to the brain, bronchial and hepatic circulation and to the testis. No effect was demonstrated on other organs studied. 4. The effect on the cerebral circulation was observed at the lowest dose of meclofenamate (0.75 mg/kg). Higher total doses were necessary for an effect on the renal and bronchial (3 mg/kg) and testicular and hepatic arteries (6 mg/kg). 5. The results suggest a variety of local vasomotor influences of renal and non-renal prostaglandins in conscious rabbits.


MicroFPGA: An affordable FPGA platform for microscope control.
Modern microscopy relies increasingly on microscope automation to improve throughput, ensure reproducibility or observe rare events. Automation requires computer control of the important elements of the microscope. Furthermore, optical elements that are usually fixed or manually movable can be placed on electronically-controllable elements. In most cases, a central electronics board is necessary to generate the control signals they require and to communicate with the computer. For such tasks, Arduino microcontrollers are widely used due to their low cost and programming entry barrier. However, they are limiting in their performance for applications that require high-speed or multiple parallel processes. Field programmable gate arrays (FPGA) are the perfect technology for high-speed microscope control, as they are capable of processing signals in parallel and with high temporal precision. While plummeting prices made the technology available to consumers, a major hurdle remaining is the complex languages used to configure them. In this work, we used an affordable FPGA, delivered with an open-source and friendly-to-use programming language, to create a versatile microscope control platform called MicroFPGA. It is capable of synchronously triggering cameras and multiple lasers following complex patterns, as well as generating various signals used to control microscope elements such as filter wheels, servomotor stages, flip-mirrors, laser power or acousto-optic modulators. MicroFPGA is open-source and we provide online Micro-Manager, Java, Python and LabVIEW libraries, together with blueprints and tutorials.


Wollaston prism with large split angle.
The image formation through a Wollaston prism with large split angle is studied. Formulas for the split angle, approximate calculations of aberrations, and ray tracings are used. The most important aberrations found are astigmatism and anamorphic distortion. Tilting the Wollaston with respect to the incident beam may reduce these aberrations, and if the orientation of the optical axis in the first element is varied it is possible to cancel one of the two aberrations for both images simultaneously, while the other one is substantially reduced. With an adequate adjustment of all the construction parameters the images become sharp enough to allow the use of large split angles (approximately 15 degrees).


Surgical Outcome of Patients Undergoing Pancreaticoduodenectomy: Analysis of a 17‒Year Experience at a Single Center.
The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patients' clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75% and 15.8% , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p<0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p<0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PD's clinical outcomes.


How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy.
Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.


Higher harmonic generation microscopy of in vitro cultured mammal oocytes and embryos.
Oocyte and embryo selection governs the success of assisted reproductive technologies. The imaging tools applied for selecting embryos may need to contain several key properties: noninvasiveness, high 3D resolution, and the contrast capability to provide as much information about the embryos as possible, such as spindle fibers, zona pellucida, and organelles. Currently adopted imaging techniques can only provide one or two of these desired properties and are with limited contrast of the embryos. Some image techniques can even damage the embryos. Previous studies have shown that harmonic generation microscopy (HGM), a virtual-transition based technology, can provide noninvasive imaging in zebrafish embryos with a sub-cellular 3D resolution and a millimeter penetration depth, and thus could be a suitable tool for future oocyte and embryo selection of assisted reproductive technologies. However to evaluate HGM in clinical use, the intrinsic contrast origin of the second harmonic generation (SHG) and third harmonic generation (THG) inside the mammal embryos has to be studied. In this work we performed HGM studies on the in vitro cultured mouse oocytes and embryos by combining the SHG and THG modalities, with a focus on the contrast origin evaluation. Through the noninvasive HGM imaging, we can clearly identify various structures in the whole oocytes and embryos, including spindle fibers, zona pellucida, polar bodies, cell membranes, and the laminated organelles in the cells. The origin of the THG contrast was further confirmed through the standard staining studies. Through SHG signals, we could not only observe the spindle fibers when the oocytes were arrested at metaphase II or during the cleavage of the embryos, but can also distinguish and analyze the thickness of the three layers of the zona pellucida. Combining two different higher-harmonic generation modalities, SHG and THG, HGM successfully revealed the sub-cellular structures of the whole mouse embryos with a high 3D spatial resolution.


Anticipatory cortico-cortical interactions: switching the task configuration between effectors.
Cognitive regulation enables a subject to plan actions according to context and to respond in a flexible manner to environmental conditions. This implies that foreknowledge about a change in system configuration will trigger preparatory activity in anticipation of the impending transformation. In the present study, we evaluate a unimanual task under two performance conditions that affected the cognitive context, and examine modulations in cortico-cortical interactions as determined by EEG coherence. The right hand movement was performed in an experimental paradigm that necessitated in some trials a voluntary and predictable switch towards a left hand movement, whereas in other trials no switch was required and movement of the right hand continued. The data showed that execution of the right hand movement was associated with an increased degree of task-related coherence in the alpha frequency band (8-12 Hz) in the switching as compared to the no switching condition, and this was most apparent for fronto-parietal connections of the movement-driving (left) as well as for the primed (right) hemisphere. For the primed hemisphere, we observed that the information flow was driven from the F4 electrode overlying the prefrontal area, which suggests that anticipatory preplanning occurred. These data indicate that higher-order cognitive operations bias cortico-cortical interactions in respect of an upcoming switch of the task settings between effectors by recruiting neural resources proactively. Dynamic adjustments in the alpha band suggest that low frequency activity is a characteristic of distributed information processing related to movement planning.


Vitamin D is a predictor of ST segment resolution and infarct size following thrombolysis in patients with acute ST elevation myocardial infarction.
Vitamin D (VitD) insufficiency is linked to various chronic conditions, including cardiovascular disease. Aim of the present study was to examine role of serum VitD in resolution of ST segment elevation (STR) in response to thrombolytic therapy following acute ST elevation myocardial infarction (STEMI). VitD was measured prospectively in all consecutive patients who were admitted with STEMI and received thrombolysis during the calendar year of 2014. STR was defined as ≥50% decrease in initial magnitude of STR 90 minutes after treatment. Multivariate binary logistic regression analysis was performed to identify effect of confounding variables on STR. Average age was 58±14 years in 227 patients (41 female and 186 male). Total of 24.7% of patients had sufficient VitD (>30 ng/mL), whereas 46.2% had VitD insufficiency (10-30 ng/mL), and remaining 29.1% had VitD deficiency (<10 ng/mL). Significant STR occurred in 57.3% of the patients. In a nonlinear pattern, serum VitD concentration directly correlated with likelihood of STR (p=0.012). VitD deficient patients had larger enzymatic infarct size compared with those with sufficient VitD (p=0.026). In multivariate logistic regression analysis, while diabetes doubled (p=0.033) and involvement of anterior wall created 2.7-fold increase in probability of nonresolution (p=0.001), for every unit increase in serum VitD, likelihood of STR increased by 2.1% (p=0.023). VitD deficiency in patients with STEMI was associated with lower occurrence of STR and larger enzymatic infarct size in response to thrombolytic therapy.


Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.


A novel variable selection approach that iteratively optimizes variable space using weighted binary matrix sampling.
In this study, a new optimization algorithm called the Variable Iterative Space Shrinkage Approach (VISSA) that is based on the idea of model population analysis (MPA) is proposed for variable selection. Unlike most of the existing optimization methods for variable selection, VISSA statistically evaluates the performance of variable space in each step of optimization. Weighted binary matrix sampling (WBMS) is proposed to generate sub-models that span the variable subspace. Two rules are highlighted during the optimization procedure. First, the variable space shrinks in each step. Second, the new variable space outperforms the previous one. The second rule, which is rarely satisfied in most of the existing methods, is the core of the VISSA strategy. Compared with some promising variable selection methods such as competitive adaptive reweighted sampling (CARS), Monte Carlo uninformative variable elimination (MCUVE) and iteratively retaining informative variables (IRIV), VISSA showed better prediction ability for the calibration of NIR data. In addition, VISSA is user-friendly; only a few insensitive parameters are needed, and the program terminates automatically without any additional conditions. The Matlab codes for implementing VISSA are freely available on the website: https://sourceforge.net/projects/multivariateanalysis/files/VISSA/.


Application of Focus Variation Microscopy and Dissolution Imaging in Understanding the Behaviour of Hydrophilic Matrices.
Hydrophilic matrix systems can be found in a wide range of extended release pharmaceutical formulations. The main principle of these systems is that upon contact with water, the hydrophilic component swells to form a hydrated gel layer which controls drug release. The following work demonstrates an explorative study into the use of dissolution imaging and focus variation microscopy with hydrophilic polymers. This study investigated the surface properties of xanthan gum (XG), polyethylene oxide (PEO), and hypromellose (hydroxypropyl methylcellulose, HPMC) compacts with each of these three hydrophilic polymers from one of each classification of natural, semi-synthetic, or synthetic polymer using a focus variation instrument. The auto correlation length (Sal) showed all surface profiles from the compacts displayed a value below 0.1 mm, indicating that only high frequency components (i.e., roughness) were considered and that the analysis had been successful. The developed interfacial area ratio (Sdr) displayed values below 5% in line with ISO guidelines for all the polymers studied with their texture aspect ratio values (Str) > 0.5, indicating uniformity of the surfaces of the produced compacts. Of the various parameters studied, areal material ratio (Smr2) predicted XG to wet and hydrate quicker than PEO, with PEO also wetting and hydrating quicker than the HPMC. The dissolution imaging and initial swelling studies proved to concur with the findings from the areal material ratio (Smr2) parameter, suggesting porosity was not an indicator for the ease with which water ingress occurs. This study suggests the Smr2 surface parameter to potentially predict wetting and initial hydration of hydrophilic polymers, however care should be taken as this study consists of a selected number of hydrophilic polymers.


Local-Area Walkability and Socioeconomic Disparities of Cardiovascular Disease Mortality in Japan.
Background There are spatial disparities in cardiovascular disease (CVD) mortality related to area-level socioeconomic status (SES) disadvantage, but little is known about the spatial distribution of CVD mortality according to built environment factors. We examined joint associations of neighborhood walkability attributes and SES with CVD mortality rates through linkage of Japanese national data sets. Methods and Results National data were used from the 1824 municipalities (of the 1880 potentially eligible municipalities) across Japan. The outcome was mortality from CVD for a 5-year period (2008-2012) for each municipality. A national index of neighborhood deprivation was used as an indicator of municipality-level SES. A national walkability index (based on population density, road density, and access to commercial areas) was calculated. Compared with higher SES municipalities, relative rates for CVD mortality were significantly higher in medium SES municipalities (relative rate, 1.05; 95% CI, 1.02-1.07) and in lower SES municipalities (relative rate, 1.09; 95% CI, 1.07-1.12). There were walkability-related gradients in CVD mortality within the high and medium SES areas, in which lower walkability was associated with higher rates of mortality; however, walkability-related CVD mortality gradients were not apparent in lower SES municipalities. Conclusions CVD mortality rates varied not only by area-level SES but also by walkability. Those living in areas of lower walkability were at higher risk of CVD mortality, even if the areas have a higher SES. Our findings provide a novel element of the evidence base needed to inform better allocation of services and resources for CVD prevention.


The Inverse Relationship Between Cancer and Alzheimer's Disease: A Possible Mechanism.
Cancer and Alzheimer's disease (AD) are both associated with aging, but do not often occur together. Obesity is a shared risk factor for both diseases and may be involved in this curious clinical observation. Fat cells produce many active substances, including leptin and adiponectin; leptin has cancer stimulating and AD inhibiting properties, while adiponectin can inhibit cancer but stimulate AD. To describe the opposing effects of leptin and adiponectin on cancer and AD, to outline signaling pathways involved in these effects and to suggest new research on effective control strategies for both diseases. A review was conducted to document the inverse cancer/AD relationship and the role of excess body fat as a common risk factor. Previous studies have suggested the involvement of p53, Wnt and other cell signaling pathways in this inverse relationship. The opposing effects of leptin and adiponectin on these signaling pathways in cancer and AD were evaluated. The inverse cancer/AD relationship is well documented, as is the role of excess body fat, especially central obesity, in increasing risk for both diseases. Leptin and adiponectin have opposing effects in cancer and AD mediated by signaling factors that influence apoptosis, angiogenesis, and other cell growth controls. Wnt and p53 are prominent among these signaling factors. Opposing effects of leptin and adiponectin, mediated by specific cell signaling pathways, are involved in the inverse cancer/Ad relationship. Future research aimed at modifying the leptin/adiponectin ratio may lead to important treatment and control approaches in both cancer and AD.


Characterization and partial purification of a factor from uremic human serum that induces insulin resistance.
We have previously shown that the incubation of normal rat adipose tissue with sera from nondialyzed, nondiabetic uremic patients reduces the transport and metabolism of glucose, in the absence and presence of insulin. In this study insulin-stimulated glucose metabolism by normal rat adipocytes was used as a bioassay to identify the resistance activity, assess the effect of chemical modification on it, and the clinical states associated with its production. The resistance activity was trypsin-labile and had an apparent isoelectric point between 6 and 7, but was not retained by either protein A or concanavalin A columns. The insulin resistance activity was decreased by coincubation with the protein synthesis inhibitor, cycloheximide. Purification to greater than 200,000-fold was attained by heating (100 degrees C) uremic serum, subjecting the supernatant to Sephadex G-25 chromatography and subsequent adsorption to DEAE at pH 7.8 and elution at pH 6.5. The partially purified resistance activity was retained within dialysis tubing of 1,000-mol wt cutoff but not within 2,000-mol wt cutoff. Hemodialysis of patients over 1 wk to 18 mo reduced significantly the amount of resistance activity in their sera. The resistance activity, present in most uremic patients, was not found in the sera of individuals with normal renal function but who were either obese, fasted, elderly or had type II diabetes mellitus. Thus, a circulating small molecular weight peptide, unique to uremia, induced insulin resistance by a protein synthesis-dependent mechanism.