Sunlight-mediated inactivation of health-relevant microorganisms in water: a review of mechanisms and modeling approaches.
Health-relevant microorganisms present in natural surface waters and engineered treatment systems that are exposed to sunlight can be inactivated by a complex set of interacting mechanisms. The net impact of sunlight depends on the solar spectral irradiance, the susceptibility of the specific microorganism to each mechanism, and the water quality; inactivation rates can vary by orders of magnitude depending on the organism and environmental conditions. Natural organic matter (NOM) has a large influence, as it can attenuate radiation and thus decrease inactivation by endogenous mechanisms. Simultaneously NOM sensitizes the formation of reactive intermediates that can damage microorganisms via exogenous mechanisms. To accurately predict inactivation and design engineered systems that enhance solar inactivation, it is necessary to model these processes, although some details are not yet sufficiently well understood. In this critical review, we summarize the photo-physics, -chemistry, and -biology that underpin sunlight-mediated inactivation, as well as the targets of damage and cellular responses to sunlight exposure. Viruses that are not susceptible to exogenous inactivation are only inactivated if UVB wavelengths (280-320 nm) are present, such as in very clear, open waters or in containers that are transparent to UVB. Bacteria are susceptible to slightly longer wavelengths. Some viruses and bacteria (especially Gram-positive) are susceptible to exogenous inactivation, which can be initiated by visible as well as UV wavelengths. We review approaches to model sunlight-mediated inactivation and illustrate how the environmental conditions can dramatically shift the inactivation rate of organisms. The implications of this mechanistic understanding of solar inactivation are discussed for a range of applications, including recreational water quality, natural treatment systems, solar disinfection of drinking water (SODIS), and enhanced inactivation via the use of sensitizers and photocatalysts. Finally, priorities for future research are identified that will further our understanding of the key role that sunlight disinfection plays in natural systems and the potential to enhance this process in engineered systems.


The use of atlas registration and graph cuts for prostate segmentation in magnetic resonance images.
An automatic method for 3D prostate segmentation in magnetic resonance (MR) images is presented for planning image-guided radiotherapy treatment of prostate cancer. A spatial prior based on intersubject atlas registration is combined with organ-specific intensity information in a graph cut segmentation framework. The segmentation is tested on 67 axial T2-weighted MR images in a leave-one-out cross validation experiment and compared with both manual reference segmentations and with multiatlas-based segmentations using majority voting atlas fusion. The impact of atlas selection is investigated in both the traditional atlas-based segmentation and the new graph cut method that combines atlas and intensity information in order to improve the segmentation accuracy. Best results were achieved using the method that combines intensity information, shape information, and atlas selection in the graph cut framework. A mean Dice similarity coefficient (DSC) of 0.88 and a mean surface distance (MSD) of 1.45 mm with respect to the manual delineation were achieved. This approaches the interobserver DSC of 0.90 and interobserver MSD 0f 1.15 mm and is comparable to other studies performing prostate segmentation in MR.


The evolution of pure alexia: a longitudinal study of recovery.
This case report documents the partial recovery, over a 12-month period, of pure alexia in an adult female following a left occipital infarction. Measures of speed and accuracy were obtained on an oral reading and a lexical decision task immediately postonset and then on 10 subsequent occasions. Explicit letter-by-letter reading was observed only during the first week poststroke but a significant effect of word length was seen in all testing sessions. Reading accuracy was relatively good at all stages and reading latency showed a remarkable decrease over time but did not reach normal reading rates. The inability to use higher-order orthographic knowledge, as manifest in the absence of a word superiority effect, was still noted at one year postonset. We therefore concluded that the change in behavior was attributable to increased proficiency in the use of the adaptive letter-by-letter procedure rather than to the resolution of the underlying deficit. It is suggested that longitudinal neurobehavioral studies add to our understanding of the alexic deficit and provide insight into the recovery process.


How people with Alzheimer's disease express their sense of self: analysis using Rom Harré's theory of selfhood.
The aim of this study was to use Harré's social constructionist theory of selfhood to describe how people with mild and moderate Alzheimer's disease (AD) express their sense of self. The findings show that Self 1, the embodied sense of being a person, was expressed fluently by participants through the use of first-person indexicals. Self 2, the experienced personal attributes and life narrative, had undergone changes. Those changes were not entirely for the worse; participants had also developed new skills in managing life with AD. In a lifetime perspective, those changes were minor and participants perceived themselves to be basically the same people that they were before having AD. When constructing Self 3, the social personae, participants usually described being supported by others, but sometimes described being exposed to malignant positioning. They also feared that they might become more exposed to negative attitudes as their AD progressed. However, participants were understanding towards the offensive behaviours of others.


Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study.
It is important to understand whether eating eggs, which are a major source of dietary choline, results in increased exposure to trimethylamine-N-oxide (TMAO), which is purported to be a risk factor for developing heart disease. We determined whether humans eating eggs generate TMAO and, if so, whether there is an associated increase in a marker for inflammation [ie, high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low-density lipoprotein (LDL). In a longitudinal, double-blind, randomized dietary intervention, 6 volunteers were fed breakfast doses of 0, 1, 2, 4, or 6 egg yolks. Diets were otherwise controlled on the day before and day of each egg dose with a standardized low-choline menu. Plasma TMAO at timed intervals (immediately before and 1, 2, 4, 8, and 24 h after each dose), 24-h urine TMAO, predose and 24-h postdose serum hsCRP, and plasma oxidized LDL were measured. Volunteers received all 5 doses with each dose separated by >2-wk washout periods. The consumption of eggs was associated with increased plasma and urine TMAO concentrations (P < 0.01), with ∼14% of the total choline in eggs having been converted to TMAO. There was considerable variation between individuals in the TMAO response. There was no difference in hsCRP or oxidized LDL concentrations after egg doses. The consumption of ≥2 eggs results in an increased formation of TMAO. Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development. Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake.


Anti-inflammatory effects of an ethanol extract of Aster glehni via inhibition of NF-κB activation in mice with DSS-induced colitis.
Although Aster glehni has been reported to prevent diabetes mellitus, hypercholesterolemia, insomnia, and cardiovascular disease, the anti-inflammatory effect of Aster glehni in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of an ethanol extract of Aster glehni (AG) in mice with dextran sulfate sodium (DSS)-induced colitis. AG significantly attenuated DSS-induced DAI scores, which implied that it suppressed diarrhea, gross bleeding, and the infiltration of immune cells. AG administration also effectively prevented shortening of the colon length and enlargement of the spleen size. Histological examinations indicated that AG suppressed colonic damage and the thickness of the muscle layer induced by DSS. In addition, AG inhibited the production of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, and the protein expression of COX-2 and iNOS in mice with DSS-induced colitis. Administration with AG suppressed the activation of nuclear factor-κB (NF-κB) including the nuclear translocation of the p65 NF-κB subunit, phosphorylation and degradation of IκB-α. Taken together, these findings suggest that the anti-inflammatory effects of AG are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic application in colitis.


Ganando Confianza: Research Focus Groups with Immigrant Mexican Mothers.
Immigrant families with children with developmental disabilities must be served using culturally sensitive approaches to service and research to maximize treatment benefits. In an effort to better understand cultural issues relevant to the provision of parenting programs for immigrant Mexican mothers of children with developmental disabilities, we conducted sustained focus groups through which we could learn more about our participants and thereby improve services. This paper reports on the challenges and lessons learned from these groups. We characterize the key lessons as (a) recruitment and retention is more than agreement to participate; (b) confidentiality is not just a word but an activity; (c) the complicated nature of language; (d) cultural norms shape the group process; (e) appreciating the value of taking time; and (f) gender issues and group interaction. Service providers and researchers who work with Mexican families may benefit from our experiences as they promote and develop programs and projects in the developmental disabilities field.


Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial.
As the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa. We conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)-immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women's retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother-infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12-0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes. In this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV. ClinicalTrials.gov NCT01933477.


All-terrain-vehicle injuries. A sport out of control.
All-terrain vehicles, originally introduced as utility vehicles to be used on farms or ranches, have now gained immense popularity in the United States as a form of recreational activity. With the increasing popularity of these vehicles, along with more powerful engines, a corresponding increase in the injury and death rates has been noted. We discuss the experience in the emergency department and trauma unit of a Southwest teaching hospital, an area where these vehicles are in use year round. We suggest ways to prevent and minimize accidents to reduce the number of injuries and deaths.


Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness.
KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4-/- mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization.


Appearance of cuboidal cells in relation to salinity in gills of Fundulus heteroclitus, a species exhibiting branchial Na+ but not Cl- uptake in freshwater.
Fundulus heteroclitus (killifish) is a model organism for ionoregulatory studies, particularly because of its opercular epithelium, although the gills are the major sites of ion exchange. Whereas Na+ and Cl- are excreted through the gills in seawater (SW), the killifish is unusual in taking up only Na+ and not Cl- at the gills in freshwater (FW). We describe morphological changes in the branchial epithelium following transfer from an acclimation medium of 10% SW to 100% SW or FW. In 10% SW, mitochondria-rich cells resemble typical seawater chloride cells (SWCCs) with accessory cells. After transfer to 100% SW, no change occurs in pavement cell (PVC) morphology or mitotic rate (measured by bromo-deoxyuridine technique), although the density of SWCC apertures increases several fold because of the uncovering of buried SWCCs by PVCs, in accord with increased rates of Na+ and Cl- efflux. After transfer to FW, PVC morphology remains unchanged, but SWCCs and accessory cells are quickly covered by PVCs, with many undergoing apoptosis or necrosis. The mitotic rate doubles by 10-14 h but typical freshwater chloride cells (FWCCs) do not appear. Instead, a wedge-shaped cell type that is moderately rich in apically oriented mitochondria, with a large ovoid nucleus, thin cytoplasmic layer, paucity of vesicular-tubular network, and variably villous surface rapidly (by 3 h) and progressively appears in the filament epithelium, by both uncovering and mitosis. This cell type is similar to that recently identified as the site of Na+ uptake in the FW trout gill. We propose the new term "cuboidal cell" for this cell, based on its morphology, to avoid confusion with traditional terminology (of PVC). We hypothesize that the cuboidal cells are the sites of active Na+ uptake in FW F. heteroclitus and suggest that the lack of Cl- uptake is attributable to the absence of typical FWCCs previously described in teleosts.


[Juniper pollen monitoring by Burkard sampler in Galveston, Texas, USA and Japanese cedar pollen counting in Fukuoka, Japan -- introduction of Pan American Aerobiology Association protocol counting technique].
We have monitored Juniper pollen which caused winter allergy symptoms by Burkard sampler in Galveston, Texas. We identified and counted Juniper pollen grains by PAAA protocol which was a comprehensive guideline for the operation of Hirst-Type suction bioaerosol sampler, (original of Burkard sampler) in the USA. In Galveston we were able to detect the Mountain Cedar (Juniperus ashei) pollen from December to of January, and Eastern Red Cedar (Juniperus virginiana) which has cross reactivity to MC from almost middle of January to February. There is no MC vegetation in Galveston. We found the pollen grains were transported from west at Edward Plateau in West Texas where it was thickly wooded. Then, we tried to monitor Japanese Cedar (JC) pollen grains in Fukuoka, Japan according with the same method. We found the significant positive correlation between the pollen counts using one single longitudinal traverse counting technique in the PAAA protocol and the JC pollen counting on the whole of Melinex tape per 24 hours (R2=0.9212, p=0.0001), and the gravitational method that is Durham sampler's pollen counting in 2002 (R2=0.489, p=0.0001), and in 2003 (R2=0.948, p=0.0001) respectively. We suggested that we can use the PAAA protocol for airborne pollen investigation in Japan by Burkard sampler.


Degeneration of hrpZ gene in Pseudomonas syringae pv. tabaci to evade tobacco defence: an arms race between tobacco and its bacterial pathogen.
The HrpZ harpin of Pseudomonas syringae is known to induce a hypersensitive response (HR) in some plants. In P. syringae pv. tabaci (Pta), the harpin gene hrpZ has been spontaneously disrupted by an internal deletion in its open reading frame and a frame shift. The loss of the ability of the recombinant harpin polypeptide of Pta to induce HR despite the high sensitivity of tobacco plants to harpin led us to investigate the meaning of the disrupted hrpZ gene in the virulence of Pta 6605. The hrpZ gene from P. syringae pv. pisi was introduced into wild-type (WT) Pta. The hrpZ-complemented Pta secreted harpin into the culture medium, but failed to cause disease symptoms by both infiltration and spray inoculation. Inoculation with the hrpZ-complemented Pta induced defence responses in tobacco plants, whereas the defence responses of tobacco plants were not prominent on inoculation with WT Pta. These results indicate that an ancestor of Pta might have disrupted hrpZ by an internal deletion to evade plant defences and confer the ability to cause disease in tobacco plants.


Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic.
Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.


Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.
Acute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains. Baseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored. PROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores. Pain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response.


Ozonation control and effects of ozone on water quality in recirculating aquaculture systems.
To address the undesired effect of chemotherapeutants in aquaculture, ozone has been suggested as an alternative to improve water quality. To ensure safe and robust treatment, it is vital to define the ozone demand and ozone kinetics of the specific water matrix to avoid ozone overdose. Different ozone dosages were applied to water in freshwater recirculating aquaculture systems (RAS). Experiments were performed to investigate ozone kinetics and demand, and to evaluate the effects on the water quality, particularly in relation to fluorescent organic matter. This study aimed at predicting a suitable ozone dosage for water treatment based on daily ozone demand via laboratory studies. These ozone dosages will be eventually applied and maintained at these levels in pilot-scale RAS to verify predictions. Selected water quality parameters were measured, including natural fluorescence and organic compound concentration changes during ozonation. Ozone reactions were described by first order kinetics. Organic matter, assessed as chemical oxygen demand and fluorescence, decreased by 25% (low O3), 30% (middle O3) and 53% (high O3), while water transmittance improved by 15% over an 8-day period. No fish mortality was observed. Overall, this study confirms that ozone can improve RAS water quality, provides a better understanding of the ozone decay mechanisms that can be used to define further safe ozone treatment margins, and that fluorescence could be used as a monitoring tool to control ozone. This study might be used as a tool to design ozone systems for full-scale RAS by analysing water sample from the specific RAS in the laboratory.


Mapping human dispersals into the Horn of Africa from Arabian Ice Age refugia using mitogenomes.
Rare mitochondrial lineages with relict distributions can sometimes be disproportionately informative about deep events in human prehistory. We have studied one such lineage, haplogroup R0a, which uniquely is most frequent in Arabia and the Horn of Africa, but is distributed much more widely, from Europe to India. We conclude that: (1) the lineage ancestral to R0a is more ancient than previously thought, with a relict distribution across the Mediterranean/Southwest Asia; (2) R0a has a much deeper presence in Arabia than previously thought, highlighting the role of at least one Pleistocene glacial refugium, perhaps on the Red Sea plains; (3) the main episode of dispersal into Eastern Africa, at least concerning maternal lineages, was at the end of the Late Glacial, due to major expansions from one or more refugia in Arabia; (4) there was likely a minor Late Glacial/early postglacial dispersal from Arabia through the Levant and into Europe, possibly alongside other lineages from a Levantine refugium; and (5) the presence of R0a in Southwest Arabia in the Holocene at the nexus of a trading network that developed after ~3 ka between Africa and the Indian Ocean led to some gene flow even further afield, into Iran, Pakistan and India.


Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.
mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC) cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs) and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.


Levers and linkages: mechanical trade-offs in a power-amplified system.
Mechanical redundancy within a biomechanical system (e.g., many-to-one mapping) allows morphologically divergent organisms to maintain equivalent mechanical outputs. However, most organisms depend on the integration of more than one biomechanical system. Here, we test whether coupled mechanical systems follow a pattern of amplification (mechanical changes are congruent and evolve toward the same functional extreme) or independence (mechanisms evolve independently). We examined the correlated evolution and evolutionary pathways of the coupled four-bar linkage and lever systems in mantis shrimp (Stomatopoda) ultrafast raptorial appendages. We examined models of character evolution in the framework of two divergent groups of stomatopods-"smashers" (hammer-shaped appendages) and "spearers" (bladed appendages). Smashers tended to evolve toward force amplification, whereas spearers evolved toward displacement amplification. These findings show that coupled biomechanical systems can evolve synergistically, thereby resulting in functional amplification rather than mechanical redundancy.


Forty-five cases of chest keloids treated with subcutaneous super-tension-reduction suture combined with postoperative electron-beam irradiation.
Chest keloids are challenging to surgeons because of their high recurrence rate. To investigate the effectiveness of the subcutaneous super-tension-reduction suture technique with postoperative electron-beam irradiation in the treatment of chest keloids. Forty-five patients with chest keloids underwent excision. To minimize the wound-closing tension, subcutaneous super-tension-reduction suture was used. The maximum tension reduction was placed on both dermis and subcutaneous tissue, which were far away from the incision. The consequence of such suturing was that the wound edges were moved centrally to elevate them like a bump after tying the buried knot. All patients received fractionated electron-beam radiation therapy starting within 24 hours after surgery, in a 5-Gy dose daily for 3 to 4 consecutive days, to a total dose of 15 to 20 Gy. The wounds healed primarily in all 45 cases. The bump at the incision began to flatten out after 2 to 3 months and was almost completely flat by 12 months postoperatively. Only 1 case of relapse (2.2%) was observed within 2 years of follow-up examination. The use of subcutaneous super-tension-reduction suture after chest keloids excision can greatly decrease tension on the dermis and the subcutaneous tissue and can, in combination with postoperative electron-beam irradiation, decrease the rate of relapse.


Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate.
Right hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC). To investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD. This is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission. Three hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P < 0.01), had lower American Society of Anesthesiology score (ASA) grade (P < 0.01) and less comorbidity (P < 0.01), but were more likely to be current smokers (P < 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P < 0.01) and frequently underwent ileocecal resection (P < 0.01) with higher rate of de-functioning/primary stoma construction (P < 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P < 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers. Patients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complications' rate was not different between the two groups.


Plant nitrogen uptake and assimilation: regulation of cellular pH homeostasis.
The enzymatic controlled metabolic processes in cells occur at their optimized pH ranges, therefore cellular pH homeostasis is fundamental for life. In plants, the nitrogen (N) source for uptake and assimilation, mainly in the forms of nitrate (NO3-) and ammonium (NH4+) quantitatively dominates the anion and cation equilibrium and the pH balance in cells. Here we review ionic and pH homeostasis in plant cells and regulation by N source from the rhizosphere to extra- and intracellular pH regulation for short- and long-distance N distribution and during N assimilation. In the process of N transport across membranes for uptake and compartmentation, both proton pumps and proton-coupled N transporters are essential, and their proton-binding sites may sense changes of apoplastic or intracellular pH. In addition, during N assimilation, carbon skeletons are required to synthesize amino acids, thus the combination of NO3- or NH4+ transport and assimilation results in different net charge and numbers of protons in plant cells. Efficient maintenance of N-controlled cellular pH homeostasis may improve N uptake and use efficiency, as well as enhance the resistance to abiotic stresses.


Wide-angle polarization-insensitive transparency of a continuous opaque metal film for near-infrared light.
Here we show that a continuous highly conducting metal film can be made transparent for wide-angle and polarization-insensitive incidence of near-infrared light by depositing periodic metal patches on top of the metal film. Based on the optimized computations, the whole system could suppress the reflection and enhance the transmission. This design of transparent metal film can be useful in applications, such as optoelectronic electrodes, solar cells, and micro-electronic displays, where both high electrical conductivity and high optical transmittance are desirable.


The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.
The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.


Is there synergy in syndemics? Psychosocial conditions and sexual risk among men who have sex with men in India.
Syndemic theory describes the clustering and synergistic interaction of disease driven by contextual and social factors, which worsen health outcomes for a population, and has been applied to men who have sex with men (MSM) and their risk for HIV and other sexually transmitted infections. Recent reviews, however, have critiqued prevailing approaches in syndemic studies that assess only additive associations without evaluation of synergy. Following these suggestions, we compared the traditional additive approach with a test for synergistic association of 5 syndemic conditions (alcohol dependence, illicit drug use, depression, intimate partner violence (IPV), and childhood sexual abuse (CSA)) with unprotected anal intercourse (UAI) and active syphilis infection among 11,771 MSM recruited through respondent driven sampling from 12 cities in India. UAI was assessed via self-report and active syphilis infection was diagnosed by RPR and THPA tests. An additive association was explored using a condition count (range 0-5), and synergy was tested using relative excess risk due to interactions (RERIs) calculated from all 2-way and common 3-way interactions between conditions in adjusted regression models. There was a significant dose response associated with the syndemic count and UAI, and a similar pattern for syphilis, though not statistically significant. RERIs showed synergy for only one pair of conditions for UAI and syphilis, respectively: IPV + depression and alcohol dependence + illicit drug use. In this study, we found an additive association between syndemic conditions and UAI with evidence of synergistic interaction between a pair of psychosocial conditions, and no significant additive association, but a synergistic interaction between another pair of psychosocial conditions for syphilis. Our results lend further support to a critical reassessment of syndemic analyses. Closer attention to the cumulative development, underlying causal pathways, and possible synergistic interaction of co-occurring epidemics through combined qualitative and quantitative methodologies may yield more effective interventions for vulnerable, marginalized populations.


Urban-rural contrasts in explanatory models and treatment-seeking behaviours for stroke in Tanzania.
Stroke is an emerging problem in sub-Saharan Africa, about which little is known since most research to date has been based on retrospective, hospital-based studies. This anthropological work, designed to complement a large community-based project on stroke incidence, focuses on local understandings and treatment-seeking behaviours in urban (Dar-es-Salaam) and rural (Hai) areas of Tanzania. Semi-structured interviews (n=80) were conducted with 20 stroke patients, 20 relatives of stroke patients, ten traditional healers, and 30 other local residents. In contrast to common expectations, and literature that finds witchcraft beliefs to be most common in rural areas, stroke in urban Dar was widely believed to emanate from supernatural causes (demons and witchcraft), while in rural Hai, explanations drew mostly on 'natural' causes (hypertension, fatty foods, stress). These different beliefs and explanatory models fed into treatment-seeking behaviours. The first option in Hai was hospital treatment, while in Dar-es-Salaam, where belief in demons led to hospital avoidance, it was traditional healers. In both sites, multiple treatment options (serially or simultaneously) were the norm. Analysis of patient and carer narratives suggested that causation beliefs outweighed other factors, such as cost and distance, in shaping effective treatment. Three policy implications are drawn. First, as other studies have also shown, it is important to engage with, rather than dismiss, local explanations and interpretations of stroke. Stroke awareness messages need to take into account the geographical and belief systems differences. Developing an understanding of explanatory models that recognizes that local beliefs arise from dynamic processes of social interaction will be critical to designing effective interventions. Second, there is a clear role for multiple healing systems with possibility of cross-reference in the case of a chronic, disabling condition like stroke, since biomedical treatment cannot offer a 'quick fix' while traditional healers can help people come to terms with their condition. Third, issues of communication between health services and their patients are particularly critical.


Development of QCM Trimethylamine Sensor Based on Water Soluble Polyaniline.
A rapid, sensitive, low-cost device to detect trimethylamine was presented in thispaper. The preparation of water soluble polyaniline was firstly studied. Then the polyanilinewas characterized via Fourier transform infrared spectroscopy (FTIR), UV-visiblespectroscopy and scanning electron microscopy (SEM). Based on the water solublepolyaniline film, a quartz crystal microbalance (QCM) sensor for trimethylamine detectionwas fabricated and its characteristics were examined. The sensor consisted of one quartzcrystal oscillator coated with the polyaniline film for sensing and the other one forreference. Pretreated with trimethylamine, the QCM sensor had an excellent linearsensitivity to trimethylamine. Easily recovered by N2 purgation, the response of the sensorexhibited a good repeatability. Responses of the sensor to trimethylamine, ethanol and ethylacetate were compared, and the results showed that the response was related to the polarityof the analyte vapor. Experimental result also showed that the sensitivity of the sensor wasrelatively stable within one month. The simple and feasible method to prepare and coat thepolyaniline sensing film makes it promising for mass production.


Studying the glycan moiety of RNase B by means of Raman and Raman optical activity.
Raman and Raman optical activity (ROA) spectroscopy are used to study the solution-phase structure of the glycan moiety of the protein ribonuclease B (RNase B). Spectral data of the intact glycan moiety of RNase B is obtained by subtracting high-quality spectral data of RNase A, the non-glycosylated form of the RNase, from the spectra of the glycoprotein. The remaining difference spectra are compared to spectra generated from Raman and ROA data of the constituent disaccharides of the RNase glycan, achieving convincing spectral overlap. The results show that ROA spectroscopy is able to extract detailed spectral data of the glycan moieties of proteins, provided that the non-glycosylated isoform is available. Furthermore, good comparison between the full glycan spectrum and the regenerated spectra based on the disaccharide data lends great promise to ROA as a tool for the solution-phase structural analysis of this structurally elusive class of biomolecules.


Cortical systems for the recognition of emotion in facial expressions.
This study is part of an effort to map neural systems involved in the processing of emotion, and it focuses on the possible cortical components of the process of recognizing facial expressions. We hypothesized that the cortical systems most responsible for the recognition of emotional facial expressions would draw on discrete regions of right higher-order sensory cortices and that the recognition of specific emotions would depend on partially distinct system subsets of such cortical regions. We tested these hypotheses using lesion analysis in 37 subjects with focal brain damage. Subjects were asked to recognize facial expressions of six basic emotions: happiness, surprise, fear, anger, disgust, and sadness. Data were analyzed with a novel technique, based on three-dimensional reconstruction of brain images, in which anatomical description of surface lesions and task performance scores were jointly mapped onto a standard brain-space. We found that all subjects recognized happy expressions normally but that some subjects were impaired in recognizing negative emotions, especially fear and sadness. The cortical surface regions that best correlated with impaired recognition of emotion were in the right inferior parietal cortex and in the right mesial anterior infracalcarine cortex. We did not find impairments in recognizing any emotion in subjects with lesions restricted to the left hemisphere. These data provide evidence for a neural system important to processing facial expressions of some emotions, involving discrete visual and somatosensory cortical sectors in right hemisphere.


Longitudinal Changes of Macular Curvature in Patients with Retinitis Pigmentosa.
To investigate the longitudinal changes of the macular curvature in eyes with retinitis pigmentosa (RP) and to determine the factors associated with the changes. We reviewed the medical charts of 107 RP patients, for whom the axial length of their right eyes ranged from 21.5 to 26.0 mm and who had had been followed by spectral-domain optical coherence tomography (OCT). The OCT images at the initial and the most recent examinations were compared. The mean curvature of Bruch's membrane within 6 mm of the central macula obtained from the OCT images was evaluated as the mean macular curvature index (MMCI). Changes in the MMCI and their relationships with other clinical factors, including the ellipsoid zone (EZ) width, were assessed. The MMCI decreased significantly in the vertical OCT images, from -15.47 × 10-5 µm-1 to -16.36 × 10-5 µm-1 (P = 0.008) during the mean observation period of 3.4 ± 1.4 years (mean ± SD). This indicated that the macular shape became more concave. The change to a steeper shape was more prominent in eyes with less photoreceptor degeneration and for which the EZ width was preserved at >2000 µm. In three eyes, the MMCI increased markedly by >5 × 10-5 µm-1, and this was accompanied by absorption of the macular edema. The macular curvature in RP eyes becomes more concave in eyes with preserved EZ width. Longitudinal changes of the macular curvature in RP should be considered in future therapies, such as the implantation of the retinal prosthesis.


The influence of coracoacromial arch anatomy on rotator cuff tears.
We performed an anatomic study of 140 cadaver shoulders to correlate the influence of the coracoacromial arch anatomy on full-thickness rotator cuff tears (RCTs). The presence, location, and size of RCTs were initially documented. After dissection was complete 14 dimensional parameters, including humeral head size, glenoid size, and location of bony landmarks, were obtained by direct measurement. These data were entered into a computerized data base and 24 additional parameters (lengths, angles, areas) were calculated. The data were then subjected to analysis of variance and paired and unpaired t tests to determine correlation between the multiple parameters, age, sex, and left-to-right variance with RCTs. Three-dimensional computer modeling was then used to investigate the role of humeral head position in defining the available space within the coracoacromial arch (supraspinatus outlet). Overall 20% of the cadaver group exhibited full-thickness RCTs. The age group 60 years and older had a 29% incidence of RCTs compared with 5% in the group less than 60 years of age. The RCT group had a significantly greater anterior projection of the acromion than had the intact group (difference = 3.8 mm, p < 0.007). Acromial tilt was 28.5° in the RCT group and 33.5° in the intact group (p < 0.007). The supraspinatus outlet area was calculated by determining the total coracoacromial arch area and subtracting the area of the humeral head within the coracoacromial arch. The supraspinatus outlet was 22.5% smaller in the RCT group (p < 0.07). By using a series of measured and calculated parameters, we were able to characterize the anatomy of the coracoacromial arch and its relationship with the humeral head and to correlate variations in structure with the presence of RCTs. These findings may aid in our understanding of outlet impingement as a factor in the cause of RCTs.


Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies.
Polyethylene glycol (PEG) is a flexible, hydrophilic simple polymer that is physically attached to peptides, proteins, nucleic acids, liposomes, and nanoparticles to reduce renal clearance, block antibody and protein binding sites, and enhance the half-life and efficacy of therapeutic molecules. Some naïve individuals have pre-existing antibodies that can bind to PEG, and some PEG-modified compounds induce additional antibodies against PEG, which can adversely impact drug efficacy and safety. Here we provide a framework to better understand PEG immunogenicity and how antibodies against PEG affect pegylated drug and nanoparticles. Analysis of published studies reveals rules for predicting accelerated blood clearance of pegylated medicine and therapeutic liposomes. Experimental studies of anti-PEG antibody binding to different forms, sizes, and immobilization states of PEG are also provided. The widespread use of SARS-CoV-2 RNA vaccines that incorporate PEG in lipid nanoparticles make understanding possible effects of anti-PEG antibodies on pegylated medicines even more critical.


Systemic vaccination with inactivated bovine virus diarrhoea virus protects against respiratory challenge.
Inactivated bovine virus diarrhoea virus, strain 11249nc, inoculated subcutaneously three times with Quil-A into calves protected against intranasal challenge with the same strain. Virus was isolated from nasopharyngeal swabs taken 4 to 8 days post challenge and blood taken 4 to 6 days post challenge from control calves but not from vaccinated calves. A second strain of virus, Ky1203nc, was selected on the basis of previously established data on its antigenicity and the amount of viral antigen produced by five cell cultures compared using an ELISA. Cultures of one cell line, MDBK, yielded a greater amount of viral antigen than the others. Strain Ky1203nc grown in MDBK cells was inactivated with beta-propiolactone, mixed with adjuvant and used as a vaccine inoculated into calves subcutaneously three times. All of 5 calves were protected against intranasal challenge with a heterologous strain. In contrast virus was isolated from nasopharyngeal swabs taken from 5 control calves and from the blood of 4 controls. All 5 control calves, but none of the vaccinates, had a leukopenia after challenge. We conclude that the selected strain and system of vaccine preparation provide an effective means of protecting calves against respiratory infection and that live vaccines are not required to protect against challenge via the respiratory tract.


The RAISE early treatment program for first-episode psychosis: background, rationale, and study design.
The premise of the National Institute of Mental Health Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) is to combine state-of-the-art pharmacologic and psychosocial treatments delivered by a well-trained, multidisciplinary team in order to significantly improve the functional outcome and quality of life for first-episode psychosis patients. The study is being conducted in non-academic (ie, real-world) treatment settings, using primarily extant reimbursement mechanisms. We developed a treatment model and training program based on extensive literature review and expert consultation. Our primary aim is to compare the experimental intervention to "usual care" on quality of life. Secondary aims include comparisons on remission, recovery, and cost-effectiveness. Patients 15-40 years old with a first episode of schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder not otherwise specified, or brief psychotic disorder according to DSM-IV and no more than 6 months of treatment with antipsychotic medications were eligible. Patients are followed for a minimum of 2 years, with major assessments conducted by blinded, centralized raters using live, 2-way video. We selected 34 clinical sites in 21 states and utilized cluster randomization to assign 17 sites to the experimental treatment and 17 to usual care. Enrollment began in July 2010 and ended in July 2012 with 404 subjects. The results of the trial will be published separately. The goal of the article is to present both the overall development of the intervention and the design of the clinical trial to evaluate its effectiveness. We believe that we have succeeded in both designing a multimodal treatment intervention that can be delivered in real-world clinical settings and implementing a controlled clinical trial that can provide the necessary outcome data to determine its impact on the trajectory of early phase schizophrenia. ClinicalTrials.gov identifier: NCT01321177.


A micropatterned elastomeric surface with enhanced frictional properties under wet conditions and its application.
Engineered surfaces that have high friction under wet or lubricated conditions are important in many practical applications. However, it is not easy to achieve stable high friction under wet conditions because a layer of fluid prevents direct solid-solid contact. Here, we report a micropatterned elastomeric surface with superior wet friction. The surface has unique arch-shaped microstructures arrayed in a circle on the surface to provide high friction on wet or flooded surfaces. The arch-shaped micropatterned surface exhibits remarkably enhanced and stable friction under wet conditions, surpassing even the performance of the hexagonal patterns of tree frogs, owing to the large contact surface and the optimal shape of drainage channels. Robotic substrate transportation systems equipped with the micropatterned surfaces can manipulate a delicate wet substrate without any sliding in a highly stable and reproducible manner, demonstrating the superior frictional capabilities of the surface under wet conditions.


Culicoides species composition and abundance on Irish cattle farms: implications for arboviral disease transmission.
Following the emergence of Schmallenberg virus (SBV) in Ireland in 2012, a sentinel herd surveillance program was established in the south of Ireland with the primary aim of investigating the species composition and abundance of Culicoides on livestock farms in the region. Ultraviolet-light trapping for Culicoides was carried out on 10 sentinel farms. Each site was sampled fortnightly over 16 weeks (21st July to 5th November 2014). One Onderstepoort Veterinary Institute UV light trap was run overnight at each site and catches were transferred immediately into 70% ethanol. Culicoides were morphologically identified to species level. Collection site habitats were characterised using the Phase 1 habitat survey technique (Joint Nature Conservation Committee). A total of 23,929 individual Culicoides from 20 species was identified, including one species identified in Ireland for the first time, Culicoides cameroni. The most abundant species identified were Culicoides obsoletus/Culicoides scoticus (38%), Culicoides dewulfi (36%), Culicoides pulicaris (9%), Culicoides chiopterus (5%) and Culicoides punctatus (5%), comprising 93% of all Culicoides specimens identified. Collection site habitats were dominated by improved grassland and a combination of broadleaf woodland and native woodland species. The most abundant species of Culicoides identified were the putative vectors of bluetongue virus (BTV) and SBV in northern Europe. Their presence and abundance demonstrates the potential for future transmission of arboviruses among livestock in this region.


Plasma biomarkers of pulmonary hypertension identified by Fourier transform infrared spectroscopy and principal component analysis.
The main goal of this study was to find specific plasma spectral markers associated with pulmonary arterial hypertension (PAH) induced by monocrotaline injection in rats. FTIR was used to monitor biochemical changes in plasma caused by PAH as compared with the systemic hypertension induced by partial ligation on the left artery and with the control group. Both pathologies, systemic and pulmonary hypertension, induced a unique response in the biochemical content of plasma, mainly related to the composition and secondary structure of plasma proteins. For PAH, β-pleated sheet components of plasma proteins were identified whereas the protein composition in systemic hypertension was dominated by unordered structures. In addition, a higher concentration of tyrosine-rich proteins was found in plasma in PAH than in systemic hypertension. The differences between both pathologies were identified also in terms of lipid composition/metabolism as well as in the content of RNA and glucose, suggesting that lipid peroxidation appears upon pulmonary hypertension development. In summary, this work demonstrates that FTIR spectroscopy supported by principal component analysis (PCA) has the potential to become a fast and non-destructive method for biochemical characterization of plasma that consequently could have a diagnostic significance in pulmonary hypertension.


Role of genotype and precore/basal core promoter mutations of hepatitis B virus in patients with chronic hepatitis B with acute exacerbation.
The results of long-term, follow-up studies show that the severity and frequency of acute exacerbation of chronic hepatitis B virus (HBV) are associated with the development of liver cirrhosis in chronic HBV infection. The aim of this study was to investigate the relationship between virological factors of HBV and the severity of acute exacerbation. Fifty-one chronic hepatitis B patients with symptomatic acute exacerbation without antiviral therapy were enrolled in the study. Genotype of HBV was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Precore (A1896) and basal core promoter (BCP) mutations (T1762 & A1764) were determined by PCR and direct sequencing. Thirty-nine patients had genotype B, 11 patients had genotype C, and 1 patient had an unclassified genotype. Thirty-two patients had precore mutation and 24 patients had BCP mutation. After adjusting for age, gender, aspartate aminotransferase (ASAT) level, albumin level, and platelet count by multiple logistic regression test, precore mutation had a protective effect on the occurrence of hepatic decompensation (p=0.046), and genotype and BCP mutations were not associated with the occurrence of hepatic decompensation. HBV precore mutation may confer less severe liver disease during acute exacerbation of chronic HBV. Genotype and BCP mutations did not have a significant association with the occurrence of hepatic decompensation.


Diffusion, spread, and migration of botulinum toxin.
Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context.


Bis- and tris-(3-aminopropyl) derivatives of 14-membered tetraazamacrocycles containing pyridine: synthesis, protonation and complexation studies.
New N-(3-aminopropyl) (L1, L2) and (2-cyanoethyl) (L3, L4) derivatives of a 14-membered tetraazamacrocycle containing pyridine have been synthesized. The protonation constants of L1 and L2 and the stability constants of their complexes with Ni2+, Cu2+, Zn2+ and Cd2+ metal ions were determined in aqueous solutions by potentiometry, at 298.2 K and ionic strength 0.10 mol dm(-3) in KNO3. Both compounds have high overall basicity due to the presence of the aminopropyl arms. Their copper(II) complexes exhibit very high stability constants, which sharply decrease for the complexes of the other studied metal ions, as usually happens with polyamine ligands. Mono- and dinuclear complexes are formed with L2 as well as with L1, but the latter exhibits mononuclear complexes with slightly higher K(ML) values while the dinuclear complexes of L2 are thermodynamically more stable. The presence of these species in solution was supported by UV-VIS-NIR and EPR spectroscopic data. The single crystal structures of [Cu(H2L2)(ClO4)]3+ and [CoL3Cl]+ revealed that the metal centres are surrounded by the four nitrogen atoms of the macrocycle and one monodentate ligand, adopting distorted square pyramidal geometries. In the [CoL3Cl]+ complex, the macrocycle adopts a folded arrangement with the nitrogen atom opposite to the pyridine at the axial position while in the [Cu(H2L2)(ClO4)]3+ complex, the macrocycle adopts a planar conformation with the three aminopropyl arms located at the same side of the macrocyclic plane.


Tailored Macroporous Hydrogels with Nanoparticles Display Enhanced and Tunable Catalytic Activity.
This work demonstrates that a model system of poly( N-isopropylacrylamide) (PNIPAam) macroporous hydrogels, with tailored microstructures and comprising gold (Au) or silver (Ag) nanoparticles, display enhanced and tunable catalytic activity. These nanocomposites are prepared using polymer templates obtained from melt-processed cocontinuous polymer blends. The reaction rate, controlled by both hydrogel porosity and the PNIPAam lower critical solution temperature, increases by more than an order of magnitude as compared to nonporous gels, and is comparable to micro- or nanocarrier-based systems, with easier catalyst recovery. The fabrication process is scalable, and is compatible with broad choices of polymer blend, gel, and nanoparticle chemistries.


Evidence that ship noise increases stress in right whales.
Baleen whales (Mysticeti) communicate using low-frequency acoustic signals. These long-wavelength sounds can be detected over hundreds of kilometres, potentially allowing contact over large distances. Low-frequency noise from large ships (20-200 Hz) overlaps acoustic signals used by baleen whales, and increased levels of underwater noise have been documented in areas with high shipping traffic. Reported responses of whales to increased noise include: habitat displacement, behavioural changes and alterations in the intensity, frequency and intervals of calls. However, it has been unclear whether exposure to noise results in physiological responses that may lead to significant consequences for individuals or populations. Here, we show that reduced ship traffic in the Bay of Fundy, Canada, following the events of 11 September 2001, resulted in a 6 dB decrease in underwater noise with a significant reduction below 150 Hz. This noise reduction was associated with decreased baseline levels of stress-related faecal hormone metabolites (glucocorticoids) in North Atlantic right whales (Eubalaena glacialis). This is the first evidence that exposure to low-frequency ship noise may be associated with chronic stress in whales, and has implications for all baleen whales in heavy ship traffic areas, and for recovery of this endangered right whale population.


Selenium-containing organic nanoparticles as silent precursors for ultra-sensitive thiol-responsive transmembrane anion transport.
An anion transporter with a selenoxide group was able to form nanoparticles in water, whose activity was fully turned off due to the aggregation effect. The formed nanoparticles have a uniform size and can be readily dispersed in water at high concentrations. Turn-on of the nanoparticles by reducing molecules is proposed to be a combined process, including the reduction of selenoxide to selenide, disassembly of the nanoparticles and location of the transporter to the lipid membrane. Accordingly, a special acceleration phase can be observed in the turn-on kinetic curves. Since turn-on of the nanoparticles is quantitatively related to the amount of reductant, the nanoparticles can be activated in a step-by-step manner. Due to the sensibility of this system to thiols, cysteine can be detected at low nanomolar concentrations. This ultra-sensitive thiol-responsive transmembrane anion transport system is quite promising in biological applications.


Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles.
Simultaneous micronization and surface modification of drug particles is considered in order to mitigate disadvantages of micronization, e.g., agglomeration, poor flowability, marginal increase in surface area and low bulk density. Particles of ibuprofen (102 μm), a model drug, pre-blended with hydrophilic nano-silica, are micronized down to 10 and 5 μm in a continuous fluid energy mill (FEM) to obtain fine surface modified particles. The solid feeding rate and the grinding pressure are shown as critical parameters for achieving the desired particle size and size distribution. The powder properties were characterized via SEM, laser scattering, powder rheometer with shear-cell, and dissolution test. Significant improvement in flow properties and dissolution rate was observed when micronization accompanied surface modification. Additionally, co-grinding with water-soluble polymer during micronization led to further increase in bulk density and more enhanced dissolution rate improvement, which is attributed to improved wettability. XRD, DSC and Raman were used to examine crystallinity, indicating minimal detectable physical transformation with FEM processed ibuprofen. The surface modified, micronized powders also showed improved dispersion, higher bulk densities (>0.4 g/ml), reduced electrostatic, and higher flowability (FFC ≥ 6) compared to just micronized powder (0.19 g/ml, FFC=1.0), indicating they may be used in high drug loaded formulations amenable to direct compression.


Jack bean (Canavalia ensiformis): nutrition related aspects and needed nutrition research.
The nutritional characteristics and food potentials of jack bean (Canavalia ensiformis) have been reviewed. The bean is a good sources of protein, 23% to 34%, and carbohydrate 55%. It is also a good source of Ca, Zn, P, Mg, Cu and Ni. Jack bean protein is adequate in most essential amino acids with the exception of methionine and cystine which may be nutritionally limiting. Antinutritional and toxic factors including trypsin inhibitors, hemagglutinins, cyanogen glucosides, oligosaccharides and others are present in jack bean. Properly processed jack bean could be used to prepare some of the popular dishes made from cowpea, peanut, pigeon pea and soybean. Industrial products such as protein concentrates and isolates, starch, flakes, grits and flours can be produced from the bean. Further research is needed to identify varieties with high protein and nutritional quality. Development of new highly nutritious food products based on whole or processed jack bean should increase production and expand use.


The advocacy in action study a cluster randomized controlled trial to reduce pedestrian injuries in deprived communities.
Road traffic-related injury is a major global public health problem. In most countries, pedestrian injuries occur predominantly to the poorest in society. A number of evaluated interventions are effective in reducing these injuries. Very little research has been carried out into the distribution and determinants of the uptake of these interventions. Previous research has shown an association between local political influence and the distribution of traffic calming after adjustment for historical crash patterns. This led to the hypothesis that advocacy could be used to increase local politicians knowledge of pedestrian injury risk and effective interventions, ultimately resulting in improved pedestrian safety. To design an intervention to improve the uptake of pedestrian safety measures in deprived communities. Electoral wards in deprived areas of England and Wales with a poor record of pedestrian safety for children and older adults. Design mixedmethods study, incorporating a cluster randomized controlled trial. Data mixture of Geographical Information Systems data collision locations, road safety interventions, telephone interviews, and questionnaires. Randomization 239 electoral wards clustered within 57 local authorities. Participants 615 politicians representing intervention and control wards. Intervention a package of tailored information including maps of pedestrian injuries was designed for intervention politicians, and a general information pack for controls. Primary outcome number of road safety interventions 25 months after randomization. Secondary outcomes politicians interest and involvement in injury prevention cost of interventions. Process evaluation use of advocacy pack, facilitators and barriers to involvement, and success.


Introduction to autoimmune neurology.
Considering the diversity and numbers of targets expressed on the estimated 500 billion glia and slightly less numerous but more diverse neurons, if any channel, receptor or protein on such a cell can be the target of the immune system, we need only imagine the possibilities. As those before us looked to the heavens and ultimately walked on the moon, we need to recognize the potential implications of autoimmune neurology - a new subspecialty in neurology that has truly launched! Its importance cannot be overstated as many of the disorders now recognized as autoimmune are treatable and reversible, representing a shift from the traditional view held by many in the lay and medical community that neurologists diagnose but don't treat! In this introductory chapter we provide a brief over-view of how the field developed, tabulate the authors and contents of the individual topics covered in each chapter, and describe some of the on-going challenges of the field.


Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions.
Solution structures of two Src homology 3 (SH3) domain-ligand complexes have been determined by nuclear magnetic resonance. Each complex consists of the SH3 domain and a nine-residue proline-rich peptide selected from a large library of ligands prepared by combinatorial synthesis. The bound ligands adopt a left-handed polyproline type II (PPII) helix, although the amino to carboxyl directionalities of their helices are opposite. The peptide orientation is determined by a salt bridge formed by the terminal arginine residues of the ligands and the conserved aspartate-99 of the SH3 domain. Residues at positions 3, 4, 6, and 7 of both peptides also intercalate into the ligand-binding site; however, the respective proline and nonproline residues show exchanged binding positions in the two complexes. These structural results led to a model for the interactions of SH3 domains with proline-rich peptides that can be used to predict critical residues in complexes of unknown structure. The model was used to identify correctly both the binding orientation and the contact and noncontact residues of a peptide derived from the nucleotide exchange factor Sos in association with the amino-terminal SH3 domain of the adaptor protein Grb2.


Evolutionarily assembled cis-regulatory module at a human ciliopathy locus.
Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.


Deficiency for the cysteine protease cathepsin L impairs Myc-induced tumorigenesis in a mouse model of pancreatic neuroendocrine cancer.
Motivated by the recent implication of cysteine protease cathepsin L as a potential target for anti-cancer drug development, we used a conditional MycERTAM;Bcl-xL model of pancreatic neuroendocrine tumorigenesis (PNET) to assess the role of cathepsin L in Myc-induced tumor progression. By employing a cysteine cathepsin activity probe in vivo and in vitro, we first established that cathepsin activity increases during the initial stages of MycERTAM;Bcl-xL tumor development. Among the cathepsin family members investigated, only cathepsin L was predominately produced by beta-tumor cells in neoplastic pancreata and, consistent with this, cathepsin L mRNA expression was rapidly upregulated following Myc activation in the beta cell compartment. By contrast, cathepsins B, S and C were highly enriched in tumor-infiltrating leukocytes. Genetic deletion of cathepsin L had no discernible effect on the initiation of neoplastic growth or concordant angiogenesis. However, the tumors that developed in the cathepsin L-deficient background were markedly reduced in size relative to their typical wild-type counterparts, indicative of a role for cathepsin L in enabling expansive tumor growth. Thus, genetic blockade of cathepsin L activity is inferred to retard Myc-driven tumor growth, encouraging the potential utility of pharmacological inhibitors of cysteine cathepsins in treating late stage tumors.


A refined taxonomy of behaviour change techniques to help people change their physical activity and healthy eating behaviours: the CALO-RE taxonomy.
Current reporting of intervention content in published research articles and protocols is generally poor, with great diversity of terminology, resulting in low replicability. This study aimed to extend the scope and improve the reliability of a 26-item taxonomy of behaviour change techniques developed by Abraham and Michie [Abraham, C. and Michie, S. (2008). A taxonomy of behaviour change techniques used in interventions. Health Psychology, 27(3), 379-387.] in order to optimise the reporting and scientific study of behaviour change interventions. Three UK study centres collaborated in applying this existing taxonomy to two systematic reviews of interventions to increase physical activity and healthy eating. The taxonomy was refined in iterative steps of (1) coding intervention descriptions, and assessing inter-rater reliability, (2) identifying gaps and problems across study centres and (3) refining the labels and definitions based on consensus discussions. Labels and definitions were improved for all techniques, conceptual overlap between categories was resolved, some categories were split and 14 techniques were added, resulting in a 40-item taxonomy. Inter-rater reliability, assessed on 50 published intervention descriptions, was good (kappa = 0.79). This taxonomy can be used to improve the specification of interventions in published reports, thus improving replication, implementation and evidence syntheses. This will strengthen the scientific study of behaviour change and intervention development.


The role of lipopolysaccharide binding protein in resistance to Salmonella infections in mice.
Polymorphonuclear leukocytes (PMN) and LPS-binding protein (LBP) are both components of the innate immune system. LBP is a plasma protein that binds to lipid A and enhances the biological activity of LPS 100- to 1000-fold. Recently it was reported that LBP-deficient mice are more susceptible to Salmonella typhimurium infection. Here we report that LBP KO mice are more susceptible to Salmonella peritonitis, but not to oral or i.v. infection. LBP knockout (KO) mice responded normally to i.p. injections of Staphylococcus aureus and casein, but not to i.p. injection of S. typhimurium or Salmonella LPS. Mice with a mutation in Toll-like receptor 4 (C3H/HeJ) have a similar defect in PMN chemotaxis. In normal mice S. typhimurium stimulated production of the CXC chemokines macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant, but levels of cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2 were greatly reduced in the LBP KO mice. LBP KO mice pretreated with casein to attract PMN in an LBP-independent manner were more resistant to Salmonella infection, but neutropenic mice were not protected by casein. Splenic TNF-alpha mRNA levels were also lower in LBP KO than in control mice infected with Salmonella. Since TNF-alpha can activate PMN, LBP KO mice may have both fewer and less active PMN in the first few hours after Salmonella are injected, making LBP KO mice more susceptible. This work confirms the importance of PMN in resistance to Salmonella infections and shows that this is facilitated by LBP.


The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO--Young Members Working Group (AIRO Giovani).
Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO--Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.


SU-E-T-595: Comparison of Volumetric Modulated Arc Therapy (VMAT) and Static Intensity Modulated Radiotherapy (IMRT) for Malignant Pleural Mesothelioma in Patients with Intact Lungs/Post Pleurectomy.
This planning study compares VMAT and static gantry, sliding window IMRT for malignant pleural mesothelioma for post pleurectomy. We compared plans for a left sided (L) and a right sided case (R). Plans used clinically approved planning target volumes (PTVs) and critical organ contours. IMRT plans employed 7-8 6 MV photon beam directions over a 215° range centered on the ipsilateral lung. VMAT plans used 4 partial arcs within the same range and energy. Prescription dose per fraction was 1.8 Gy; case L went to 50.4 Gy, case R to 46.8 Gy. Planning objectives were: Lyman model NTCP for both lungs < 25%; contralateral lung, mean dose < 8 Gy; heart, V30 Gy < 50%, mean < 30 Gy; Each Kidney, V18 Gy < 33%; liver_not_GTV, mean < 30 Gy, V30 Gy < 50%; stomach not PTV, mean < 30 Gy; cord maximum < 45 Gy; bowel maximum < 55 Gy, D05 < 45 Gy; PTV D95 = 94%, V95 = 94%, D05 = 115%. Dose calculation was done with the AAA algorithm. VMAT and IMRT both met the dosimetric constraints. The VMAT MU were 887 (L)_and 896 (R) and for IMRT were 1691 (L) and 2409 (R). IMRT required 14-16 fields (wide-field splitting). The delivery times were 8 minutes (VMAT) and 20 minutes (IMRT). For coverage and plan homogeneity parameters within 1.5% - 2%, VMAT better spared organs at risk. Both VMAT and IMRT are feasible techniques for the treatment of malignant pleural mesothelioma with intact lungs, with less MU and a shorter delivery time for VMAT. Additional cases must be planned to test generality of our preliminary results.


Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks.
The CDC recommends that healthcare settings provide influenza patients with facemasks as a means of reducing transmission to staff and other patients, and a recent report suggested that surgical masks can capture influenza virus in large droplet spray. However, there is minimal data on influenza virus aerosol shedding, the infectiousness of exhaled aerosols, and none on the impact of facemasks on viral aerosol shedding from patients with seasonal influenza. We collected samples of exhaled particles (one with and one without a facemask) in two size fractions ("coarse">5 µm, "fine"≤5 µm) from 37 volunteers within 5 days of seasonal influenza onset, measured viral copy number using quantitative RT-PCR, and tested the fine-particle fraction for culturable virus. Fine particles contained 8.8 (95% CI 4.1 to 19) fold more viral copies than did coarse particles. Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold (95% CI 1.5 to 5.2) and in the coarse fraction by 25 fold (95% CI 3.5 to 180). Overall, masks produced a 3.4 fold (95% CI 1.8 to 6.3) reduction in viral aerosol shedding. Correlations between nasopharyngeal swab and the aerosol fraction copy numbers were weak (r = 0.17, coarse; r = 0.29, fine fraction). Copy numbers in exhaled breath declined rapidly with day after onset of illness. Two subjects with the highest copy numbers gave culture positive fine particle samples. Surgical masks worn by patients reduce aerosols shedding of virus. The abundance of viral copies in fine particle aerosols and evidence for their infectiousness suggests an important role in seasonal influenza transmission. Monitoring exhaled virus aerosols will be important for validation of experimental transmission studies in humans.


IgY technology: extraction of chicken antibodies from egg yolk by polyethylene glycol (PEG) precipitation.
Hens can be immunized by means of i.m. vaccination (Musculus pectoralis, left and right, injection volume 0.5-1.0 ml) or by means of Gene-Gun plasmid-immunization. Dependent on the immunogenicity of the antigen, high antibody-titres (up to 1:100,000 - 1:1,000,000) can be achieved after only one or 3 - 4 boost immunizations. Normally, a hen lays eggs continuously for about 72 weeks, thereafter the laying capacity decreases. This protocol describes the extraction of total IgY from egg yolk by means of a precipitation procedure (PEG. Polson et al. 1980). The method involves two important steps. The first one is the removal of lipids and the second is the precipitation of total IgY from the supernatant of step one. After dialysis against a buffer (normally PBS) the IgY-extract can be stored at -20°C for more than a year. The purity of the extract is around 80 %, the total IgY per egg varies from 40-80 mg, dependent on the age of the laying hen. The total IgY content increases with the age of the hen from around 40 mg/egg up to 80 mg/egg (concerning PEG precipitation). The laying capacity of a hen per year is around 325 eggs. That means a total potential harvest of 20 g total IgY/year based on a mean IgY content of 60 mg total IgY/egg (see Table 1).


Does money relieve depression? Evidence from social pension expansions in China.
We estimate the impact of pension enrollment on mental well-being using China's New Rural Pension Scheme (NRPS), the largest existing pension program in the world. Since its launch in 2009, more than 400 million Chinese have enrolled in the NRPS. We first describe plausible pathways through which pension may affect mental health. We then use the national sample of China Family Panel Studies (CFPS) to examine the effect of pension enrollment on mental health, as measured by CES-D and self-reported depressive symptoms. To overcome the endogeneity of pension enrollment or of income change on mental health, we exploit geographic variation in pension program implementation. Results indicate modest to large reductions in depressive symptoms due to pension enrollment; this effect is more pronounced among individuals eligible to claim pension income, among populations with more financial constraints, and among those with worse baseline mental health. Our findings hold for a rich set of robustness checks and falsification tests.


Antimicrobial defences in Drosophila: the story so far.
Drosophila has recently emerged as an important model for the study of innate immunity. Two signalling pathways triggered by different classes of microorganisms control its antimicrobial defence. This phenomenon has been recently shown to reflect specificity in pathogen recognition and in subsequent induction of the systemic immune response. In the following we will review recent developments in the field, which give a more defined picture of how the Drosophila innate immune system works both in terms of microbe perception and effector molecules, as well as point to the missing pieces of the puzzle.


15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau.
In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.


Tobacco-Cessation Interventions and Attributes of Individual and Organizational Excellence in Acute Care.
Despite years of reducing tobacco use, few studies describe to what extent evidence-based tobacco-cessation interventions are a standard of acute and critical care nursing practice using the US Public Health Service 5 A's framework: ask, advise, assess, assist, and arrange. To identify relationships between the 5 A's framework, attributes of individual and organizational excellence, and intention to integrate tobacco-cessation interventions as a standard of daily practice among nurses. Nurses attending the American Association of Critical-Care Nurses National Teaching Institute were invited to complete a 21-item survey. Data were gathered in Boston, Orlando, and Chicago in a 3-year period. Descriptive statistics and logistic regression were used for data analysis. Among 1773 completed surveys, nurses from organizations with standing orders for tobacco dependence were 5 times more likely to have high confidence in their 5 A's skills (odds ratio, 5.037; 95% CI, 3.429-7.400; P < .001) and 3.4 times more likely to have high intentions to integrate tobacco cessation into their daily practice (odds ratio, 3.421; 95% CI, 1.765-6.628; P < .001). Nurses with certifications were more likely to want to learn how to integrate tobacco-cessation interventions (odds ratio, 1.676; 95% CI, 0.990-2.836; P = .05). Opportunities abound to create strategies leveraging attributes of nursing and organizational excellence to promote evidence-based approaches to improve health outcomes in acutely and critically ill tobacco-dependent populations.


Regression modeling of the North East Atlantic Spring Bloom suggests previously unrecognized biological roles for V and Mo.
In order to identify the biogeochemical parameters controlling pCO2, total chlorophyll a, and dimethyl sulfide (DMS) concentrations during the North East Atlantic Spring Bloom (NASB), we used previously unpublished particulate and dissolved elemental concentrations to construct several linear regression models; first by hypothesis-testing, and then with exhaustive stepwise linear regression followed by leave-one-out cross-validation. The field data was obtained along a latitudinal transect from the Azores Islands to the North Atlantic, and best-fit models (determined by lowest predictive error) of up to three variables are presented. Total chlorophyll a is predicted best by biomass (POC, PON) parameters and by pigments characteristic of picophytoplankton for the southern section of the sampling transect (from the Azores to the Rockhall-Hatton Plateau) and coccolithophores in the northern portion (from the Rockhall-Hatton Plateau to the Denmark Strait). Both the pCO2 and DMS models included variables traditionally associated with the development of the NASB such as mixed-layer depth and with Fe, Si, and P-deplete conditions (dissolved Fe, dissolved and biogenic silica, dissolved PO(3-)4). However, the regressions for pCO2 and DMS also include intracellular V and Mo concentrations, respectively. Mo is involved in DMS production as a cofactor in dimethylsulfoxide reductase. No significant biological role for V has yet been determined, although intracellular V is significantly correlated (p-value <0.05) with biogenic silica (R(2) = 0.72) and total chlorophyll a (R(2) = 0.49) while the same is not true for its biogeochemical analogue Mo, suggesting active uptake of V by phytoplankton. Our statistical analysis suggests these two lesser-studied metals may play more important roles in bloom dynamics than previously thought, and highlights a need for studies focused on determining their potential biological requirements and cell quotas.


Aryl hydrocarbon receptor is required for optimal B-cell proliferation.
The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr-/-) B cells proliferate less than AhR-sufficient (Ahr+/+) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr-/- B cells are outcompeted by Ahr+/+ cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.


The National Adult Inpatient Survey conducted in the English National Health Service from 2002 to 2009: how have the data been used and what do we know as a result?
When it was initiated in 2001, England's national patient survey programme was one of the first in the world and has now been widely emulated in other healthcare systems. The aim of the survey programme was to make the National Health Service (NHS) more "patient centred" and more responsive to patient feedback. The national inpatient survey has now been running in England annually since 2002 gathering data from over 600,000 patients. The aim of this study is to investigate how the data have been used and to summarise what has been learned about patients' evaluation of care as a result. Two independent researchers systematically gathered all research that included analyses of the English national adult inpatient survey data. Journals, databases and relevant websites were searched. Publications prior to 2002 were excluded. Articles were also identified following consultation with experts. All documents were then critically appraised by two co-authors both of whom have a background in statistical analysis. We found that the majority of the studies identified were reports produced by organisations contracted to gather the data or co-ordinate the data collection and used mainly descriptive statistics. A few articles used the survey data for evidence based reporting or linked the survey to other healthcare data. The patient's socio-demographic characteristics appeared to influence their evaluation of their care but characteristics of the workforce and the. At a national level, the results of the survey have been remarkably stable over time. Only in those areas where there have been co-ordinated government-led campaigns, targets and incentives, have improvements been shown. The main findings of the review are that while the survey data have been used for different purposes they seem to have incited little academic interest. The national inpatient survey has been a useful resource for many authors and organisations but the full potential inherent in this large, longitudinal publicly available dataset about patients' experiences has not as yet been fully exploited.This review suggests that the presence of survey results alone is not enough to improve patients' experiences and further research is required to understand whether and how the survey can be best used to improve standards of care in the NHS.


Immunological aspects of sport nutrition.
Prolonged bouts of exercise and heavy training regimens are associated with depression of immune system functions that can increase the risk of picking up opportunistic infections such as the common cold and influenza. Some common sport nutrition practices including high-carbohydrate diets and carbohydrate ingestion during exercise, training with low-glycogen stores, intentional dieting for weight loss, ingestion of high-dose antioxidant supplements and protein ingestion post exercise may influence immune system status in athletes. In order to maintain robust immunity, athletes need to consume a well-balanced diet that is sufficient to meet their requirements for energy, carbohydrate, protein and micronutrients. Dietary deficiencies of protein and specific micronutrients are well known to be potential causes of immune dysfunction and an adequate intake of some essential minerals including iron and zinc and the vitamins A, D, E, B6 and B12 are important to maintain a healthy immune function. Vitamin D may be a particular concern as recent studies have emphasised its importance in limiting infection episode incidence and duration in both the general population and in athletes and many individuals exhibit inadequate vitamin D status during the winter months. There is only limited evidence that individual amino acids, β-glucans, herbal extracts and zinc are capable of boosting immunity or reducing infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotics, vitamin D3, bovine colostrum and plant polyphenol containing supplements or foodstuffs currently offer the best chance of success, particularly for those individuals who are prone to illness.


Imaging biomarker roadmap for cancer studies.
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.