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Background: Enhanced recovery protocols (ERPs) after metabolic and bariatric surgery (MBS) may help decrease length of stay (LOS) and postoperative nausea/vomiting but implementation is often fraught with challenges. The primary aim of this pilot study was to standardize a MBS ERP with a real-time data support dashboard and checklist and assess impact on global and individual element compliance. The secondary aim was to evaluate 30 day outcomes including LOS, hospital readmissions, and re-operations. Methods and procedures: An ERP, paper checklist, and virtual dashboard aligned on MBS patient care elements for pre-, intra-, and post-operative phases of care were developed and sequentially deployed. The dashboard includes surgical volumes, operative times, ERP compliance, and 30 day outcomes over a rolling 18 month period. Overall and individual element ERP compliance and outcomes were compared pre- and post-implementation via two-tailed Student's t-tests. Results: Overall, 471 patients were identified (pre-implementation: 193; post-implementation: 278). Baseline monthly average compliance rates for all patient care elements were 1.7%, 3.7%, and 6.2% for pre-, intra-, and post-operative phases, respectively. Following ERP integration with dashboard and checklist, the intra-operative phase achieved the highest overall monthly average compliance at 31.3% (P < 0.01). Following the intervention, pre-operative acetaminophen administration had the highest monthly mean compliance at ≥ 99.1%. Overall TAP block use increased 3.2-fold from a baseline mean rate of 25.4–80.8% post-implementation (P < 0.01). A significant decrease in average intra-operative monthly morphine milligram equivalents use was noted with a 56% drop pre- vs. post-implementation. Average LOS decreased from 2.0 to 1.7 days post-implementation with no impact on post-operative outcomes. Conclusion: Implementation of a checklist and dashboard facilitated ERP integration and adoption of process measures with many improvements in compliance but no impact on 30 day outcomes. Further research is required to understand how clinical support tools can impact ERP adoption among MBS patients. [ABSTRACT FROM AUTHOR]

When compared to tide-dominated shelves, shelves swept by geostrophic flows are relatively understudied, yet geostrophic currents have the potential to construct substantial current-generated shelf bedforms. This paper examines the evolution of a series of bedforms encountered along the narrow Agulhas Current-swept northern KwaZulu-Natal shelf. Their evolution is placed in the context of progressive current impingement and variation in flows associated with the postglacial transgression and culminating in the present-day highstand. Ultra-high resolution seismic reflection, multibeam, side-scan sonar and single beam data sets reveal several bedform scales and morphologies; wave ripples and shoreface-connected ridges are associated only with the inner shelf, and 2D and 3D very large dunes are more cosmopolitan and span the entire shelf sector. The inner shelf is marked by rock outcrop (aeolianite), surrounded by sandy sediment, grading seaward into sediment starved bedforms associated with bioclastic gravels. Where sufficient sediment exists in local depocenters, very large dunes form discontinuous fields along the outer shelf. The seismic stratigraphy of the outer shelf reflects the effects of postglacial flooding by rising sea levels and increasing current impingement by the Agulhas Current. The Holocene wave ravinement surface is overlain by flat-lying strata (early dune development and dune amalgamation with first current exposure), in turn covered by hummocky, sub-horizontal aggrading beds (amalgamation), overlain by inclined cross-bedded packages (lee faces of the bedforms formed during migration and full current interaction). Morphometric analyses show that for both the inner and outer shelf, no relationships exist between water depth, wavelength and spacing. Height to spacing (H/L) relationships are weak but nevertheless show a broadly positive trend. Bedform heights are lower on the inner shelf compared to the outer shelf, but bedform spacing is greater on the inner shelf, with a 40% overlap in H/L indices observed between the two areas. The departures in overlap can be linked to the competing offshore Agulhas Current and the inshore wave-dominated processes. Bedforms of the inner shelf plot below the global H/L mean and can be related to the more infrequent incursions of the Agulhas Current core. At the time of survey, the Agulhas Current was likely situated well offshore, resulting in reduced current activity in the survey area resulting in rounding of the dune crests, degradation of the dune crests and trough infilling. On the outer shelf, the H/L values plot above the mean global trend, suggesting vertical accretion due to the faster currents. Crest rounding and downlapping of the upstream lee faces onto the downstream stoss faces indicate dune degradation, which is related to a seaward location of the Agulhas Current at the time of survey. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD. [ABSTRACT FROM AUTHOR]

Hall effect and quantum oscillation measurements on high temperature cuprate superconductors show that underdoped compositions have small Fermi surface pockets whereas when heavily overdoped, a single much larger pocket is found. The origin of this change in electronic structure has been unclear, but may be related to the high temperature superconductivity. Here we show that the clean overdoped single-layer cuprate Tl2Ba2CuO6+δ (Tl2201) displays CDW order with a remarkably long correlation length ξ ≈ 200 Å which disappears above a hole doping of pCDW ≈ 0.265. We show that the evolution of the electronic properties of Tl2201 as the doping is lowered may be explained by a Fermi surface reconstruction which accompanies the emergence of the CDW below pCDW. Our results demonstrate importance of CDW correlations in understanding the electronic properties of overdoped cuprates. The origin of the Fermi surface reconstruction that occurs in cuprate superconductors as hole doping increases remains unclear. Here, the authors observe long range charge density wave (CDW) order in the overdoped single-layer cuprate Tl2Ba2CuO6+δ, which then disappears above a hole concentration 0.265, suggesting a correlation between Fermi surface reconstruction and the emergence of the CDW. [ABSTRACT FROM AUTHOR]

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1–6, an inverse Hall angle that varies as temperature squared7–9 and a linear-in-field magnetoresistance10–13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant ‘Planckian’ dissipators.Measurements of high-field magnetotransport in overdoped cuprates indicate that the strange-metal regime exists beyond the critical doping, and that it has both coherent and incoherent contributions. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. While most PD cases are idiopathic, the known genetic causes of PD are useful to understand common disease mechanisms. Recent data suggests that autophagy is regulated by protein acetylation mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities. The changes in histone acetylation reported to be involved in PD pathogenesis have prompted this investigation of protein acetylation and HAT and HDAC activities in both idiopathic PD and G2019S leucine-rich repeat kinase 2 (LRRK2) cell cultures. Fibroblasts from PD patients (with or without the G2019S LRRK2 mutation) and control subjects were used to assess the different phenotypes between idiopathic and genetic PD. G2019S LRRK2 mutation displays increased mitophagy due to the activation of class III HDACs whereas idiopathic PD exhibits downregulation of clearance of defective mitochondria. This reduction of mitophagy is accompanied by more reactive oxygen species (ROS). In parallel, the acetylation protein levels of idiopathic and genetic individuals are different due to an upregulation in class I and II HDACs. Despite this upregulation, the total HDAC activity is decreased in idiopathic PD and the total HAT activity does not significantly vary. Mitophagy upregulation is beneficial for reducing the ROS-induced harm in genetic PD. The defective mitophagy in idiopathic PD is inherent to the decrease in class III HDACs. Thus, there is an imbalance between total HATs and HDACs activities in idiopathic PD, which increases cell death. The inhibition of HATs in idiopathic PD cells displays a cytoprotective effect. [ABSTRACT FROM AUTHOR]

On the SE African shelf, a submerged shoreline at a depth of 60 m is examined and its attributes compared between two shelf sectors with different morphologies, yet similar energy regimes. The aim is to assess the controls of antecedent conditioning on shoreline development and later preservation from transgressive ravinement. Using a combination of multibeam bathymetry and single-channel seismic profiles, the stratigraphy and morphology of the shoreline is investigated. Low-gradient bedrock examples reveal several distinctive seismic facies, including onlapping chaotic reflector packages which are interpreted as calcarenite rubble fields. These palaeo-shorelines possess planform equilibrium morphologies, including parabolic dunes and blowout forms along with relict shore platforms. They are strongly associated with incised valleys of last glacial maximum age which underlie the shoreline locations; these provide wide, back -barrier accommodation space during transgression. In contrast, palaeo-shorelines on the steeper-gradient shelf have a simpler stratigraphic arrangement. They are not as well preserved, are generally covered by thick drapes of sediment, and lack the elaborate planform morphologies of their lower-shelf gradient equivalents. Isolated incised valleys and the steep bedrock gradient limit accommodation space. The comparison indicates that antecedent bedrock slope and available accommodation are amongst the dominant controls on overstepping, and thus potential preservation, of palaeo-shorelines on the shelf. Lower-gradient shelves not only promote rapid shoreline translation but, together with wide, sandy back -barrier accommodation, also foster larger barrier volumes. In suitable climates such as in the Mediterranean and other sub-tropical areas, the ensuing shoreline stability promotes rapid and effective cementation of the barrier. In comparison, steep bedrock profiles with limited back -barrier accommodation have much lower preservation potential. Transgressive ravinement is more focussed on steep slopes, effectively removing more material during the ravinement process. The more dynamic environment may also reduce the effectiveness of diagenesis. The potential of beachrock and aeolianite palaeo-shorelines as submerged sea-level indicators may be optimal in low-gradient settings in Mediterranean to subtropical environments. [ABSTRACT FROM AUTHOR]

This study examines a Holocene-aged submerged shoreline, Limestone Reef, located in the shallow subtidal zone of South Africa's east coast. It comprises an elongate, coast-oblique, slab-like outcrop of beachrock situated above the contemporary fair-weather wave base. It is currently undergoing mechanical disintegration. Its unique and rare preservation in a high-energy setting affords an opportunity to examine the mechanical processes occurring during wave ravinement associated with rising sea level. The submerged shoreline and the adjacent shoreface were examined using high-resolution seismic reflection, side-scan sonar and shallow-water multibeam echosounding techniques. Limestone Reef rests on top of unconsolidated Holocene deposits. The structure's surface is characterised by reef-perpendicular gullies with rubble derived from the slab fringing its seaward edge. Limestone Reef slopes gently seawards and has a steep landward-facing edge where gullies are most prominently developed. Teardrop-shaped rippled scour depressions, marked by high backscatter, are located seawards of the submerged shoreline. These elongate in a seaward direction and are filled with bioclastic gravels and residual rubble from Limestone Reef. The gullies in the upstanding structure are indicative of wave plucking and abrasion of the shoreline. The material exposed by the rippled scour depressions is identical to that comprising the postglacial ravinement surface identified in the offshore stratigraphy. These deposits are considered to represent the contemporary, actively forming wave ravinement surface. The results suggest that wave ravinement of submerged shorelines is a discontinuous process dominated by the seaward entrainment of material from its landward edge controlled by high-energy drawback during storm surges. The ravinement process appears to operate at the seasonal scale and averages out over the long-term millennial scale for the continuous surface. [ABSTRACT FROM AUTHOR]

Organic farming systems need to replace nutrients exported via farm products, especially phosphorus (P) which may otherwise become depleted in soil in the long term. In Europe, EU regulations for organic production are shaping the farming systems with respect to inputs of nutrients. Permitted off-farm P sources include conventional animal manure, composted or anaerobically digested organic residues, rock phosphate, and some animal residues such as meat and bone meal. The recent proposed revision of EU regulations for organic production (2014) puts less emphasis on closing nutrient cycles and instead aims at minimizing off-farm inputs, to reduce the risk of importing contaminants. This development, which has received little attention from the organic sector so far, is explained here. The paper further explores the regulatory conditions that govern the P supply to organic agriculture in six European countries: Austria, Denmark, Germany, Great Britain, Norway, and Switzerland. Organic farmers are subject to substantial variation in standards arising from the interpretation of EU regulations into national laws, restrictions imposed by private actors such as retailers, and private standards which may be stricter than EU regulations. In several countries, the majority of organic farmers are certified by private, stricter standards. We propose that EU regulations and private standards for organic production should not limit the use of recycled fertilizers in organic farming systems, as long as means are taken to ensure the quality and safety of these inputs. Awareness of the need to close nutrient cycles may contribute to adapting regulations and private standards to support recycling of nutrients from society to organic agriculture. A better definition of the term 'natural substance' in organic regulations is required. [ABSTRACT FROM AUTHOR]

Dietary fatty acids (FA) act as signaling molecules with diverse effects on physiologic function. The aim of this article is to review and summarize the clinical human studies in the literature on how dietary FA composition in meals and diets affects hunger and satiety signaling in the body. Studies examining FA saturation (monounsaturated (MUFA), saturated or polyunsaturated (PUFA) FAs) or FA chain length from high-fat meals/diets were included. Measures of appetite included visual analog scale (VAS) questionnaires, appetite hormones (Cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), gastric insulinotropic polypeptide gastric inhibitory peptide (GIP), ghrelin, leptin, insulin) and/or energy intake (EI) data. VAS measures in 9 out of 13 studies were not influenced by FA saturation. PUFAs, followed by MUFAs, tended to induce the greatest stimulatory effect on GLP-1, GIP and PYY, which was found in 6 out of 11 studies measuring appetite-related hormones. Regarding FA chain length, five of six studies show either no difference or less hunger (VAS) and greater satiety hormone levels (two of six studies) for FAs with longer chain lengths. EI does not seem to be affected by the saturation of FAs while EI was inconclusive for studies comparing FA chain length. Possibly due to the inconsistencies in study design, little agreement is observed between the studies on the impact of FA composition on hormonal and subjective measures of appetite as well as EI. Therefore, more research on the long-term impact of dietary FA composition on appetite control may provide clearer outcomes. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Spinal anaesthesia (SA) and general anaesthesia (GA) are widely used techniques for vaginal surgery for pelvic floor disorders with inconclusive evidence of the superiority of either. We conducted a randomised controlled trial (RCT) to assess the feasibility of a full scale RCT aiming to examine the effect of anaesthetic mode for vaginal surgery on operative, patient reported and length of hospital stay (LOHS) outcomes. Methods: Patients undergoing vaginal surgery, recruited through a urogynaecology service in a University teaching hospital, were randomised to receive either GA or SA. Patients were followed up for 12 weeks postoperatively. Pain was measured on a visual analogue scale; nausea was assessed with a four-point verbal rating scale. Patient's subjective perception of treatment outcome, quality of life (QoL) and functional outcomes were assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ) on vaginal symptoms and the SF-36 questionnaire. Results: Sixty women were randomised, 29 to GA and 31 to SA. The groups were similar in terms of age and type of vaginal surgery performed. No statistically significant differences were noted between the groups with regard to pain, nausea, quality of life (QoL), functional outcomes as well as length of stay in the postoperative recovery room, use of analgesia postoperatively and LOHS. Conclusion: This study has demonstrated that a full RCT is feasible and should focus on the length of hospital stay in a subgroup of patients undergoing vaginal surgery where SA may help to facilitate enhanced recovery or day surgery. [ABSTRACT FROM AUTHOR]

This special issue of Geo-Marine Letters comprises seven contributions to the session 'Stratigraphic and morphologic signatures of continental shelves' of the 35th International Geological Congress held in Cape Town (Republic of South Africa) on 27 August-4 September 2016. There is an additional article not presented at the conference but falling into the same general theme. The guest editors are A.N. Green and J.A.G. Cooper. The eight articles address several contemporary themes in continental shelf geology. They include the role of antecedent conditioning on the development of shelf stratigraphy and geomorphology; erosion of submerged shorelines and their preservation during (stepped) postglacial sea-level rise; the role of glacial processes (e.g. iceberg scouring during ice-sheet retreat); and the utility of archival data in addressing contemporary issues such as Holocene climate change and global oceanographic circulation systems. The continental shelf holds important information for understanding past and present global circulation and earth-ice-atmosphere interactions including sea-level change. It is hoped that these themes will spur further research that is slowly coming to the fore in several new and innovative mapping and exploration programmes emerging from an increasing number of coastal nations. [ABSTRACT FROM AUTHOR]

Background: The Hall technique for placement of preformed metal crowns is widely used in the UK for the management of decayed primary molar teeth. The creation of space is achieved by the placement of orthodontic separators adjacent to the tooth requiring restoration. Highlighting the first reported case of an abrasion caused by dental floss, this communication describes the clinical findings of an 8-year-old patient following placement of orthodontic separators. Case report: An 8-year old boy attended the University Dental Hospital of Manchester for placement of orthodontic separators prior to restoration URE, ULE, LLE, and LRE with preformed metal crowns using the hall technique. The following week he presented with a 2cm abrasion to his right cheek, which had been caused by dental floss used in placement of the orthodontic separators. Follow up: Conservative advice was given and the lesion had resolved completely at a 2-week review. Conclusion: This case is a timely reminder of the importance of adequate lip retraction and soft tissue management during placement of orthodontic separators. [ABSTRACT FROM AUTHOR]

Serotonin toxicity results from serotonin excess in the central nervous system from serotonergic drugs. Previous studies suggest an association between T102C polymorphism of the serotonin 2A (5-hydroxytryptamine 2A) receptor gene and serotonergic adverse effects with serotonergic drugs. We aimed to determine whether there is an association between the T102C polymorphism and serotonin toxicity in patients taking serotonergic drug overdoses. Ninety-five patients presenting with serotonergic drug overdoses were examined for serotonin toxicity and had blood collected for DNA analysis. A diagnosis of serotonin toxicity was made in 14 patients (15%) based on the Hunter Serotonin Toxicology Criteria. Four of the 14 patients (29%) with serotonin toxicity had the C/C genotype compared with 20/81 (25%) without serotonin toxicity. There were no differences in age or sex, but the median defined daily dose taken by patients with serotonin toxicity was 27 (14-84) compared with 18 (2-136) in patients without serotonin toxicity (P=0.06). There was no association between serotonin toxicity and the T102C polymorphism in patients taking a serotonergic drug overdose. [ABSTRACT FROM AUTHOR]

Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common single-nucleotide polymorphism (SNP) most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs, we would predict better response in patients without the risk allele, because they have increased CACNA1C expression. [ABSTRACT FROM AUTHOR]

An implantable sensor of intracranial pressure is described. It measures the difference in pressure between the extradural space and the scalp. This pressure difference modulates the resonant frequency (in the range 7·9-8·6 MHz) of a tuned circuit which can be interrogated by external equipment. The implant is filled with 0·9% sodium chloride solution and made mainly of silicone rubber. [ABSTRACT FROM AUTHOR]

Following an introduction on the determinants of the outcome of schizophrenia and review of some prediction studies, this paper presents the results of prognostic statements made for 88 first onset schizophrenic patients in terms of their duration of episode, length of stay in hospital, occupational capacity and functioning in the family. Predicted outcome was compared with the actual results after one year. Clinical judges were found to make reasonably accurate predictions about the short term outcome of schizophrenia and their statements were better than chance agreements. [ABSTRACT FROM AUTHOR]

The association of pancreatoblastoma and Wiedemann-Beckwith syndrome has not been noted previously. In this report we describe a child with Wiedemann-Beckwith syndrome who had a pancreatoblastoma resected on day 27 of life. He is also the first reported case of Wiedemann-Beckwith syndrome in a black baby. [ABSTRACT FROM AUTHOR]

Bacterial Foraging Optimisation (BFO) is investigated in an attempt to evaluate its use in solving complex optimisation problems for aeronautical structures. A hybrid variant of BFOA, which incorporates meta-modelling techniques, is also proposed and employed. The efficiency and effectiveness of the methods are tested for tailoring a rectangular composite wing, aiming to maximise the flutter speed and for scaling a joined-wing aircraft, targeting to match aeroelastic responses between the physical prototype and wind tunnel model. The obtained results are compared with those found using a range of other biologically inspired optimisation methods (GA, PSO, ACO), proving that the social foraging behavior of motile bacteria is an effective tool for aeroelastic optimisation. [ABSTRACT FROM AUTHOR]

As the fraction of electricity generation from intermittent renewable sources-such as solar or wind-grows, the ability to store large amounts of electrical energy is of increasing importance. Solid-electrode batteries maintain discharge at peak power for far too short a time to fully regulate wind or solar power output. In contrast, flow batteries can independently scale the power (electrode area) and energy (arbitrarily large storage volume) components of the system by maintaining all of the electro-active species in fluid form. Wide-scale utilization of flow batteries is, however, limited by the abundance and cost of these materials, particularly those using redox-active metals and precious-metal electrocatalysts. Here we describe a class of energy storage materials that exploits the favourable chemical and electrochemical properties of a family of molecules known as quinones. The example we demonstrate is a metal-free flow battery based on the redox chemistry of 9,10-anthraquinone-2,7-disulphonic acid (AQDS). AQDS undergoes extremely rapid and reversible two-electron two-proton reduction on a glassy carbon electrode in sulphuric acid. An aqueous flow battery with inexpensive carbon electrodes, combining the quinone/hydroquinone couple with the Br2/Br− redox couple, yields a peak galvanic power density exceeding 0.6 W cm−2 at 1.3 A cm−2. Cycling of this quinone-bromide flow battery showed >99 per cent storage capacity retention per cycle. The organic anthraquinone species can be synthesized from inexpensive commodity chemicals. This organic approach permits tuning of important properties such as the reduction potential and solubility by adding functional groups: for example, we demonstrate that the addition of two hydroxy groups to AQDS increases the open circuit potential of the cell by 11% and we describe a pathway for further increases in cell voltage. The use of π-aromatic redox-active organic molecules instead of redox-active metals represents a new and promising direction for realizing massive electrical energy storage at greatly reduced cost. [ABSTRACT FROM AUTHOR]

Once a Urolepis rufipes male mounted, the female beat her antennae against his mouth and clypeus. Immediately after he swept his antennae rapidly downward and extruded his mouthparts, her abdomen rose as she opened her genital orifice. Almost simultaneously he backed up for copulation and she folded her antennae against her head. Neither her abdomen rising nor her antennal folding were essential to his backing up as determined from their timing and from experiments in which her abdomen was sealed or her antennae were removed. Females did not open their genital orifice if with a sealed-mouth male; and antennae-removed females did not open even in the few cases where untreated males extruded their mouthparts. Unlike a closely related species, females mounted by sealed-mouth males did not open in response to air from containers of mating pairs. [ABSTRACT FROM AUTHOR]

α-Synuclein is a central component of the pathogenesis of Parkinson's disease (PD). Phosphorylation at serine-129 represents an important post-translational modification and constitutes the major form of the protein in Lewy bodies. Several kinases have been implicated in the phosphorylation of α-synuclein. The targeting of kinase pathways as a potential to influence the pathogenesis of PD is an important focus of attention, given that mutations of specific kinases (LRRK2 and PINK1) are causes of familial PD. Pramipexole (PPX) is a dopamine agonist developed for the symptomatic relief of PD. Several in vitro and in vivo laboratory studies have demonstrated that PPX exerts neuroprotective properties in model systems of relevance to PD. The present study demonstrates that PPX inhibits the phosphorylation of α-synuclein and that this is independent of dopamine receptor activation. PPX blocks the increase in phosphorylated α-synuclein induced by inhibition of the ubiquitin proteasomal system. The phosphorylation of α-synuclein occurs in part at least through casein kinase 2, and PPX in turn reduces the phosphorylation of this enzyme, thereby inhibiting its activity. Thus, PPX decreases the phosphorylation of α-synuclein, and this mechanism may contribute to its protective properties in PD models. [ABSTRACT FROM AUTHOR]

Background/objectives:Identifying critical periods of greater weight gain could provide useful information to combat the obesity epidemic. We tested whether body weight (BW), body fat percentage (BF%) and blood pressure (BP) changed during the holiday season (thanksgiving to new year's day) and the impact of regular exercise on these parameters.Subjects/methods:A total of 48 males and 100 females (age 18-65 years) with a mean body mass index of 25.1±0.5 kg/m2 were evaluated in mid-November (visit 1) and early January (visit 2; across 57±0.5 days). Anthropometric data, BF%, BP and self-reported exercise were recorded.Results:Participants showed significant increases in BW (0.78±0.1 kg, P<0.001, 95% confidence interval (CI): 0.57-0.99), BF% (0.5±0.2%, P=0.007, 95% CI: 0.12-0.77), systolic blood pressure (SBP; 2.3±1.2 mm Hg, P=0.048, 95% CI: 0.01-4.63) and diastolic blood pressure (1.8±0.8 mm Hg, P=0.028, 95% CI: 0.20-3.49). Obese participants (35.2±0.8 kg/m2) showed a greater increase in BF% compared with normal weight participants (21.7±0.2 kg/m2, P<0.05, 95% CI: 0.53-2.37) and a trend vs overweight participants (26.8±0.3 kg/m2, P=0.07, 95% CI: −0.18-1.65). Exercise (4.8±0.6 h per week) did not protect against holiday weight gain and was not a significant predictor for changes in BW or BF%. Data are reported as means±s.e.CONCLUSION:Our participants gained an average of 0.78 kg, which indicates the majority of average annual weight gain (1 kg/y) reported by others may occur during the holiday season. Obese participants are most at risk as they showed the greatest increases in BF%. Initial BW, not exercise, significantly predicted BF% and BW gain. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the molecular synergy between somatic mutations in acute myeloid leukemia (AML), such as internal tandem duplications of FLT3 (FLT3-ITD) and Nucleophosmin (NPM1) exon 12 mutations (NPM1c), which induce AML in mice.

Imaging and spectroscopy of the solar corona, coupled with polarimetry, are the only tools available at present to capture signatures of physical processes responsible for coronal heating and solar wind acceleration within the first few solar radii above the solar limb. With the recent advent of improved detector technology and image processing techniques, broad-band white light and narrow-band multi-wavelength observations of coronal forbidden lines, made during total solar eclipses, have started to yield new views about the thermodynamic and magnetic properties of coronal structures. This paper outlines these unique capabilities, which until present, have been feasible primarily with observations during natural total solar eclipses. This work also draws attention to the exciting possibility of greatly increasing the frequency and duration of solar eclipse observations with Moon orbiting observatories utilizing lunar limb occultation of the solar disk for coronal measurements. [ABSTRACT FROM AUTHOR]

There is concern over the sustainability and environmental impact of mineral fertilisers and crop protection inputs used in intensive arable crop production systems. However, replacing mineral with organic fertilisers (animal and green manures) and restricting the use of chemosynthetic crop protection may significantly reduce crop yields. The effects of (a) replacing mineral with composted cattle manure fertiliser input and (b) omitting pesticide-based crop protection on potato ( Solanum tuberosum) tuber yield, leaf and tuber mineral nutrient content and leaf protein profiles were investigated. Switching to organic fertiliser had a greater effect on yield and protein profiles than the omission of chemosynthetic crop protection. Leaf N and P composition were significant drivers of protein expression, particularly proteins involved in photosynthesis such as the large subunit of RuBisCO, RuBisCO activase and the photosystem I reaction centre, which were at higher abundances in potato leaves grown under mineral fertiliser regimes. Proteins known to be induced in response to stress, such as dehydroascorbate reductase and Glutathione S-transferases, were also shown to be up-regulated under mineral fertilisation, possibly associated with higher Cd composition, whereas two proteins known to be involved in biotic stress (1,3-β- d-glucan glucanohydrolase; putative Kunitz-type tuber invertase inhibitor) were more abundant under compost fertilisation. Results showed that switching from mineral to organic fertilisers led to reduced N availability, a significant change in leaf protein expression and lower tuber yield. In contrast, omission of chemosynthetic crop protection inputs had limited effects on protein expression and no significant effect on tuber yield. This study provides information on the effects of changes in nutrient supply on protein expression patterns. It is a prerequisite for the development of functional molecular markers for a directed strategy to inform breeding programmes to improve potato nutrient use efficiency. [ABSTRACT FROM AUTHOR]

Background and aims: Aerobic exercise capacity appears impaired in children with inflammatory bowel disease (IBD). Whether this holds true in adults with IBD is not known. Using cardiopulmonary exercise testing (CPET), we assessed anaerobic threshold (AT) in such patients comparing data with reference values and other elective surgical patients. We also sought to confirm whether the presence of a fistula further reduced AT. Methods: CPET was performed between November 2007 and December 2010 on patients awaiting abdominopelvic surgery. Gender-specific normal reference values were used for comparison. Unadjusted comparison between two groups was made using Mann-Whitney U test and by unpaired t test. Data were adjusted by analysis of covariance, using age and sex as covariates. Differences between patients' observed values and reference values were tested using paired t tests. Results: Four hundred and fourteen patients (234 male) were studied (mean ± SD age, 56.6 ± 16.4 years; weight, 74.2 ± 15.6 kg). Adjusted AT values in Crohn's disease (CD) were lower than colorectal cancer (11.4 ± 3.4 vs 13.2 ± 3.5 ml.kg.min, p = 0.03) and for all other colorectal disease groups combined (12.6 ± 3.5 ml.kg.min, p = 0.03). AT of Ulcerative colitis (UC) and CD patients together were reduced compared to population reference values ( p < 0.05). Conclusion: After adjusting for age and sex, CD patients had a reduced AT compared to patients with colorectal cancer and other colorectal disease groups combined. The pathogenesis of this low AT remains to be defined and warrants further investigation. [ABSTRACT FROM AUTHOR]

Aerobic exercise increases 24-h fat oxidation following initiation of a high-fat diet. The objective of this study is to examine the time course of increased fat oxidation under exercise and sedentary conditions. Eighteen healthy subjects completed a randomized crossover design (sedentary and exercise visits) staying for five consecutive days in a metabolic chamber each visit. On day 1, 30% of energy intake was from fat; days 2-5 had 50% of energy as fat. During exercise, subjects rode on a stationary cycle at 45% of VOmax for 1 h in the mornings and evenings. Respiratory gases and urinary nitrogen were collected to calculate macronutrient oxidation and non-protein respiratory exchange ratio (NPRER). This data, collected continuously (24-h periods), were subsequently divided into three time segments: (1) exercise + recovery (1000-1200 hours, 2100-2200 hours), (2) sleep (2300-0645 hours), and (3) wake (all remaining hours). NPRER on exercise versus sedentary visits was lower for the sleep segment (0.77 ± 0.01 01 vs. 0.81 ± 0.01, p < 0.001), higher for the exercise + recovery segment (0.88 ± 0.01 vs. 0.86 ± 0.01, p < 0.001), and was not different for the wake segment. Fat oxidation was significantly higher for exercise versus sedentary treatments during sleep (41 ± 2 vs. 31 ± 2 g), wake (62 ± 3 vs. 51 ± 3 g), and exercise + recovery segments (33 ± 3 vs.16 ± 1 g), but so was fat intake by design (171 ± 8 vs. 128 ± 7 g/d). Although exercise showed greater fat oxidation during all segments, dietary fat intake was also higher. Therefore, based on NPRER, the time of day during which the exercise treatment increased the ratio of fat to carbohydrate oxidation was during sleep. [ABSTRACT FROM AUTHOR]

The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development. [ABSTRACT FROM AUTHOR]

In cell and animal models, telomere erosion promotes chromosomal instability via breakage-fusion-bridge cycles, contributing to the early stages of tumorigenesis. However, evidence involving short telomeres in cancer development in humans is scarce, epidemiological and indirect. Here we directly implicate telomere shortening as a critical molecular event for malignant evolution in aplastic anemia (AA). Patients' telomere lengths at diagnosis of AA, while comparable to age-matched controls, inversely correlated with the probability of developing a cytogenetically abnormal clone. A significantly increased number of telomere signal-free chromosomal ends and chromosomal numerical and structural abnormalities were observed in bone marrow cells of patients with shorter telomeres in comparison with patients with longer telomeres and healthy subjects. The proportion of monosomy-7 cells in the bone marrow at diagnosis of AA inversely correlated with telomere length, years before the emergence of an autonomous and clinically detectable abnormal clone. Marrow cells of clinically healthy individuals carrying loss-of-function telomerase mutations and with extremely short telomeres also showed chromosomal instability in vitro. These results provide the first clinical direct evidence in humans that short telomeres in hematopoietic cells are dysfunctional, mediate chromosomal instability and predispose to malignant transformation in a human disease. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study. Methods: We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent-child trios for analysis. We tested for association using the transmission disequilibrium test. Results: Seventeen of the 18 susceptibility loci reached nominal levels of significance ( p < 0.05) in the expanded family collection, with 14q24.1 just falling short ( p = 0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance ( p < 2.8 × 10). All susceptibility loci had consistent direction of effects with the original study. Conclusions/interpretation: The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed. [ABSTRACT FROM AUTHOR]

Neurocritical care is a subspecialty of critical care medicine, dedicated to the care and the advancement of care of critically ill patients with neurosurgical or neurological diseases. Neurocritical care patients are heterogeneous, in both their disease process and the therapies they receive, however, several studies demonstrate that care of these patients in dedicated NeuroIntensive Care Units (neuroICUs) by neurointensivists, who coordinate their care is associated with reduced mortality and resource utilization. NeuroICUs foster innovation, and yet despite all the recent advances, much research needs to be undertaken in neurocritical care to better understand the disease pathophysiology and to demonstrate improved outcome with the use of goal-directed therapy based on evolving techniques and therapies. [ABSTRACT FROM AUTHOR]

ims/hypothesis: We quantified the effect of ADRA2A (encoding α-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies. Methods: Genotype data for ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 were analysed in >17,000 individuals (1,307 type 2 diabetes cases) with regard to metabolic traits and type 2 diabetes risk. Two studies ( n = 9,437), genotyped using the Human Cardiovascular Disease BeadChip, provided 12 additional ADRA2A SNPs. Results: Rs553668 was associated with per allele effects on fasting glucose (0.03 mmol/l, p = 0.016) and type 2 diabetes risk (OR 1.17, 95% CI 1.04-1.31; p = 0.01). No significant association was observed with rs10885122. Of the 12 SNPs, several showed associations with metabolic traits. Overall, after variable selection, rs553668 was associated with type 2 diabetes risk (OR 1.38, 95% CI 1.09-1.73; p = 0.007). rs553668 (per allele difference 0.036 mmol/l, 95% CI 0.008-0.065) and rs17186196 (per allele difference 0.066 mmol/l, 95% CI 0.017-0.115) were independently associated with fasting glucose, and rs17186196 with fasting insulin and HOMA of insulin resistance (4.3%, 95% CI 0.6-8.1 and 4.9%, 95% CI 1.0-9.0, respectively, per allele). Per-allele effects of rs491589 on systolic and diastolic blood pressure were 1.19 mmHg (95% CI 0.43-1.95) and 0.61 mmHg (95% CI 0.11-1.10), respectively, and those of rs36022820 on BMI 0.58 kg/m (95% CI 0.15-1.02). Conclusions/interpretation: Multiple ADRA2A SNPs are associated with metabolic traits, blood pressure and type 2 diabetes risk. The α-2 adrenergic receptor should be revisited as a therapeutic target for reduction of the adverse consequences of metabolic trait disorders and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Recent advances in the statistical analysis of microsatellite data permit calculation of sex-specific dispersal rates through sex- and age-specific comparisons of genetic variation. This approach, developed for the analysis of data derived from co-dominant autosomal markers, should be applicable to a sex-specific marker such as mitochondrial DNA. To test this premise, we amplified a 449 bp control region DNA sequence from the mitochondrial genome of the collared peccary (Pecari tajacu), and estimated intra-class correlations among herds sampled from three Texas populations. Analyses on data partitioned by breeding group showed a clear signal of male-biased dispersal; sex-specific fixation indices associated with genetic variation among social groups within populations yielded values for females (FGP=0.91), which were significantly larger than values for males (FGP=0.24; P=0.0015). The same general pattern emerged when the analyses were conducted on age classes (albeit nonsignificantly), as well as categories of individuals that were predicted a posteriori to be dispersers (adult males) and philopatric (adult females and all immatures). By extending a previously published methodology based on biparentally inherited markers to matrilineally inherited haploid data, we calculated sex-specific rates of contemporary dispersal among social groups within populations (m♂=0.37). These results support the idea that mitochondrial DNA haplotype frequency data can be used to estimate sex-specific instantaneous dispersal rates in a social species. [ABSTRACT FROM AUTHOR]

A candidate gene study was conducted on 10 established type II diabetes genes and 45 genes associated with autoimmune diseases, including type I diabetes (T1D), in a maximum of 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. Associations at P values <10−3 were found for three known T1D regions at chromosomes 4q27, 12q13.2 and 12q24.13 (http://www.T1DBase.org). Support was obtained for a newly identified T1D candidate locus on chromosome 12q13.3–12q14.1 (rs1678536/KIF5A: P=8.1 × 10−3; relative risk (RR) for minor allele=0.89, 95% CI=0.82–0.97), which has a separate association from the previously reported T1D candidate locus ERBB3/12q13.2–q13.3. Our new evidence adds to that previously published for the same gene region in a T1D case–control study (rs1678542; P=3.0 × 10−4; odds ratio (OR)=0.92, 95% CI=0.88–0.96). This region, which contains many genes, has also been associated with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The advent of genome-wide association (GWA) studies has revolutionized the detection of disease loci and provided abundant evidence for previously undetected disease loci that can be pooled together in meta-analysis studies or used to design follow-up studies. A total of 1715 SNPs from the Wellcome Trust Case Control Consortium GWA study of type I diabetes (T1D) were selected and a follow-up study was conducted in 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. In addition to the support for previously identified loci (PTPN22/1p13; ERBB3/12q13; SH2B3/12q24; CLEC16A/16p13; UBASH3A/21q22), evidence supporting two new and distinct chromosome locations associated with T1D was observed: FHOD3/18q12 (rs2644261, P=5.9 × 10−4) and Xp22 (rs5979785, P=6.8 × 10−3; http://www.T1DBase.org). There was independent support for both SNPs in a GWA meta-analysis of 7514 cases and 9045 controls (P values=5.0 × 10−3 and 6.7 × 10−6, respectively). The chromosome 18q12 region contains four genes, none of which are obvious functional candidate genes. In contrast, the Xp22 SNP is located 30 kb centromeric of the functional candidate genes TLR8 and TLR7 genes. Both TLR8 and TLR7 are functional candidate genes owing to their key roles as pathogen recognition receptors and, in the case of TLR7, overexpression has been associated directly with murine autoimmune disease. [ABSTRACT FROM AUTHOR]

We used recently confirmed type 2 diabetes gene regions to investigate the genetic relationship between type 1 and type 2 diabetes, in an average of 7,606 type 1 diabetic individuals and 8,218 controls, providing >80% power to detect effects as small as an OR of 1.11 at a false-positive rate of 0.003. The single nucleotide polymorphisms (SNPs) with the most convincing evidence of association in 12 type 2 diabetes-associated gene regions, PPARG, CDKAL1, HNF1B, WFS1, SLC30A8, CDKN2A–CDKN2B, IGF2BP2, KCNJ11, TCF7L2, FTO, HHEX–IDE and THADA, were analysed in type 1 diabetes cases and controls. PPARG and HHEX–IDE were additionally tested for association in 3,851 type 1 diabetes families. Tests for interaction with HLA class II genotypes, autoantibody status, sex, and age-at-diagnosis of type 1 diabetes were performed with all 12 gene regions. Only PPARG and HHEX–IDE showed any evidence of association with type 1 diabetes cases and controls ( p = 0.004 and p = 0.003, respectively; p > 0.05 for other SNPs). The potential association of PPARG was supported by family analyses ( p = 0.003; pcombined = 1.0 × 10−4). No SNPs showed evidence of interaction with any covariate ( p > 0.05). We found no convincing genetic link between type 1 and type 2 diabetes. An association of PPARG (rs1801282/Pro12Ala) could be consistent with its known function in inflammation. Hence, our results reinforce evidence suggesting that type 1 diabetes is a disease of the immune system, rather than being due to inherited defects in beta cell function or regeneration or insulin resistance. [ABSTRACT FROM AUTHOR]

The European Recommendation on Integrated Coastal Zone Management has six core principles. These form two groups, one concerned with strategic goals and one that has a local focus. The principles are presented as a menu of free-standing options, with no prioritization either within or between groups. In the case of coastal erosion management these characteristics result in irreconcilable conflicts, and actively hinder sustainable management of eroding coasts. The principles require clarification, and recognition that they are an indivisible integrated set which should not be used to select principles to advance a particular agenda. It is essential that the strategic principles are given priority, because only they can underpin a sustainable approach to the issue of coastal erosion. [ABSTRACT FROM AUTHOR]

The relationship between BP and microalbuminuria in young people with type 1 diabetes is not completely clear. As microalbuminuria is preceded by a gradual rise in albumin excretion within the normal range, we hypothesised that ambulatory BP (ABP) may be closely related to albumin excretion and progression to microalbuminuria. ABP monitoring (ABPM) was performed in 509 young people with type 1 diabetes (age median [range]: 15.7 [10.7–22.6] years) followed with annual assessments of three early morning urinary albumin:creatinine ratios (ACRs) and HbA1c. Systolic BP (SBP) and diastolic BP (DBP) and the nocturnal fall in BP were analysed in relation to ACR. All ABPM variables were significantly related to baseline log10 ACR ( p < 0.001). After the ABPM evaluation, 287 patients were followed for a median of 2.2 (1.0–5.5) years. ABP at baseline was independently related to mean ACR during follow-up. Nineteen initially normoalbuminuric patients developed microalbuminuria after 2.0 (0.2–4.0) years and their baseline daytime DBP was higher than in normoalbuminuric patients ( p < 0.001). After adjusting for baseline ACR and HbA1c, there was an 11% increased risk of microalbuminuria for each 1 mmHg increase in daytime DBP. Forty-eight per cent of patients were non-dippers for SBP and 60% for DBP; however, ACR was not different between dippers and non-dippers and there were no differences in the nocturnal fall in BP between normoalbuminuric and future microalbuminuric patients. In this cohort of young people with type 1 diabetes, ABP was significantly related to ACR, and daytime DBP was independently associated with progression to microalbuminuria. Increasing albumin excretion, even in the normal range, may be associated with parallel rises in BP. [ABSTRACT FROM AUTHOR]