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In active volcanic arcs such as the Andean volcanic mountain belt, magmatically sourced fluids are channeled through the brittle crust by faults and fracture networks. In the Andes, volcanoes, geothermal springs, and major mineral deposits have a spatial and genetic relationship with NNE trending, margin‐parallel faults and margin‐oblique, NW trending Andean Transverse Faults (ATF). The Tinguiririca and Planchón‐Peteroa volcanoes in the Andean Southern Volcanic Zone (SVZ) demonstrate this relationship, as their spatially associated thermal springs show strike alignment to the NNE oriented El Fierro Thrust Fault System. We constrain the fault system architecture and its interaction with volcanically sourced hydrothermal fluids using a combined magnetotelluric (MT) and seismic survey that was deployed for 20 months. High‐conductivity zones are located along the axis of the active volcanic chain, delineating fluids and/or melt. A distinct WNW trending cluster of seismicity correlates with resistivity contrasts, considered to be a reactivated ATF. Seismicity occurs below 4 km, suggesting activity is limited to basement rocks, and the cessation of seismicity at 9 km delineates the local brittle‐ductile transition. As seismicity is not seen west of the El Fierro fault, we hypothesize that this structure plays a key role in compartmentalizing magmatically derived hydrothermal fluids to the east, where the fault zone acts as a barrier to cross‐fault fluid migration and channels fault‐parallel fluid flow to the surface from depth. Increases in fluid pressure above hydrostatic may facilitate reactivation. This site‐specific case study provides the first three‐dimensional seismic and MT observations of the mechanics behind the reactivation of an ATF. Key Points: In the Andean volcanic arc, margin‐parallel and blind oblique fault systems control volcanic, hydrothermal, and ore‐porphyry processesSubsurface conductivity structure and seismicity show a WNW trending active fault in the Andean Southern Volcanic ZoneResults show magmatic/hydrothermal fluids are compartmentalized by local faults and elevated fluid pressures promote fault reactivation [ABSTRACT FROM AUTHOR]

Aims: Galanin is a highly inducible neuroprotective neuropeptide and in Alzheimer's disease (AD), a network of galaninergic fibres has been reported to hypertrophy and hyperinnervate the surviving cholinergic neurons in the basal forebrain. We aimed to determine (i) the extent of galanin hyperinnervation in patients with AD and Lewy body disease and (ii) whether galanin expression relates to the neuropathological burden and cholinergic losses. Methods: Galanin immunohistochemistry was carried out in the anterior nucleus basalis of Meynert of 27 Parkinson's disease (PD) cases without cognitive impairment (mild cognitive impairment [MCI]), 15 with PD with MCI, 42 with Parkinson's disease dementia (PDD), 12 with Dementia with Lewy bodies (DLB), 19 with AD, 12 mixed AD/DLB and 16 controls. Galaninergic innervation of cholinergic neurons was scored semiquantitatively. For a subgroup of cases (n = 60), cholinergic losses were determined from maximum densities of choline acetyltransferase positive (ChAT+ve) neurons and their projection fibres. Quantitative data for α‐synuclein, amyloid beta and tau pathology were obtained from tissue microarrays covering cortical/subcortical regions. Results: Significant losses of cholinergic neurons and their projection fibres were observed across all diseases. Galaninergic hyperinnervation was infrequent and particularly uncommon in established AD and DLB. We found that hyperinnervation frequencies are significantly higher in the transition between PD without MCI to PDD and that higher burdens of co‐existent AD pathology impair this galaninergic response. Conclusions: Our results suggest that galanin upregulation represents an intrinsic response early in Lewy body diseases but which fails with increasing burdens of AD related pathology. [ABSTRACT FROM AUTHOR]

The fundamental principle of veganism is to avoid all possible animal exploitation and therefore, animal ethics has always been a primary motivator. Nowadays, the environment and health are also common motivators. Omission of all animal products leads to dietary exclusion of vitamin B12, limited intake of omega-3 fatty acids, specifically EPA and DHA, and intake of low bioavailable iron sources1. Obtaining the knowledge to appropriately plan and replace nutrients through food or supplementation is key to avoiding deficiencies and subsequent consequences. This study aimed to determine the effect of motivation for being vegan on intake of key nutrients and nutritional knowledge. This cross-sectional, observational study recruited participants, who had followed a vegan diet for minimum 2 years. Demographics and nutrition knowledge were obtained from questionnaires. Motivation type was determined using the validated vegetarian eating motives inventory (VEMI) – participants scored the importance of animal ethic, environment and health. Intakes of vitamin B12 and iron, were collected using a 4-day food diary and assessed against Estimated Average Requirement (EAR). Blood samples were taken to determine status of vitamin B12, haemoglobin, serum ferritin, and omega-3 index. Omega-3 index score ≤4 indicates increased risk of coronary heart disease. Animal ethics was the greatest motivator to become vegan, with 83.5% of participants scoring it as very important, compared to 71.7% of people stating the environment, and 53.3% stating health. No association was found between all motivation types and intake of vitamin B12 and iron, nor omega-3 index. Mean vitamin B12 intake (supplements excluded) of 2.11ug/day ± 3.43 exceeded the EAR of 2.0ug/day for both men and women, however intakes ranged between 0.00 and 37.63ug/day. Mean intake of iron (18.77mg/day) exceeded the EAR for both men and women. Overall mean omega-3 index was 3.16%. Both men (162.24g/L) and women (151.44g/L) had adequate mean Hb serum concentrations. Mean serum ferritin was within normal range for both men (64.86ug/L ± 43.48) and women (32.55ug/L ± 26.04). Overall mean serum vitamin B12 was within normal range (316.54pmol/L ± 146.18), however a large range was observed from 72.00pmol/L to 1,015pmol/L. Males and females had similar knowledge, with only one question regarding fibre content in cornflakes found to be significantly different (P = 0.012). Knowledge was varied e.g., 100% of participants could identify that pasta was a carbohydrate source, yet could not identify which fats are most important to reduce. Mean vitamin B12 intake exceeding EAR and normal status despite limited vegan sources, indicates high consumption of high bioavailable fortified foods, and supplementation. Iron status shows large consumption of iron rich foods to overcome bioavailability issues, reflected by adequate iron intake, after increasing EAR by 80% to meet recommendations. The mean omega-3 index shows a low cardioprotective omega-3 fatty acid intake. [ABSTRACT FROM AUTHOR]

The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains. [ABSTRACT FROM AUTHOR]

Purpose (1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification. Methods Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5–15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2–7 weeks. Results The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2–7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79). Conclusion The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type. [ABSTRACT FROM AUTHOR]

Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert, it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB has an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. We have reviewed the history and anatomy of the nvlDBB and now propose guidelines for distinguishing nvlDBB from other neighbouring cholinergic cell groups for standardizing future clinicopathological work. Thorough review of the literature regarding neurodegenerative conditions reveals inconsistent results in terms of cholinergic neuronal loss within the nvlDBB. This is likely to be due to the use of variable neuronal inclusion criteria and omission of cholinergic immunohistochemical markers. Extrapolating from those studies showing a significant nvlDBB neuronal loss in Lewy body dementia, we propose an anatomical and functional connection between the cholinergic component of the nvlDBB (Ch2) and the CA2 subfield in the hippocampus which may be especially vulnerable in Lewy body disorders. [ABSTRACT FROM AUTHOR]

Objectives To determine the utility of an in-practice test kit to detect protective serum antibody against canine distemper virus, canine adenovirus and canine parvovirus type 2 in a sample of the UK dog population. Materials and Methods Serum samples from 486 dogs, last vaccinated between less than 1 month and 124 months previously, were tested with the VacciCheck™ test kit for protective antibodies against distemper, adenovirus and parvovirus type 2. Results A high proportion of the dogs tested (93·6%) had protective antibody against all three of the core vaccine antigens: 95·7% of the dogs were seropositive against canine distemper virus, 97·3% against canine adenovirus and 98·5% against canine parvovirus type 2. The small number of dogs that were seronegative for one or more of the antigens ( n = 31) may have had waning of previous serum antibody or may have been rare genetic non-responders to that specific antigen. Clinical Significance UK veterinarians can be reassured that triennial revaccination of adult dogs with core vaccines provides long-lived protective immunity. In-practice serological test kits are a valuable tool for informing decision-making about canine core revaccination. [ABSTRACT FROM AUTHOR]

Few studies have investigated nitrogen (N) fertilizer management in no-tillage (NT) tobacco (Nicotiana tobacum L.) production systems, even though N fertilization is known to influence tobacco cured leaf yield and quality. The present study evaluated how tillage practice and N fertilizer rate affected burley tobacco agronomic performance, plant available nitrogen (PAN) supply, and leaf chemical constituents. In 2012 and 2013, three N fertilizer rates (0, 140 and 280 kg N/ha) were introduced as split-plots within a long-term NT and conventional tillage (CT) (mouldboard plough) comparison study. Results (2007–2013) showed that the effect of tillage on tobacco yield depended on seasonal weather; NT tobacco appeared to have lower yield than CT tobacco in seasons with <450 mm growing season rainfall, but similar yields when rainfall was >500 mm. In 2012 (432 mm rainfall; 84% of the long-term seasonal mean), leaf SPAD reading, leaf nitrate concentration, total nitrogen concentration at the topping day (i.e. removal of flowers/buds at the tops of the plants) and cured leaf nicotine and alkaloid content suggested that N deficiency was more pronounced in NT than CT at the lowest N fertilizer rate. The PAN supply, as measured by a modified in situ resin core method, was similar in 2012 between NT and CT, suggesting that plant factors may have had a role in N uptake efficiency. This scenario did not repeat in 2013 (706 mm rainfall; 137% of the long-term seasonal mean). Even though N fertilization rates were identical for both tillage practices in 2012 and 2013, PAN was lower, on average, in 2012. Because N uptake is largely the result of mass flow, the impact of reduced root density in NT tobacco would be expected to be more pronounced in a season such as 2012, when water was limited. Banding N close to the tobacco root system and/or side-dressing some portion of N may be recommended strategies to improve N use efficiency in NT burley tobacco production. [ABSTRACT FROM PUBLISHER]

Aims CLARITY is a novel technique which enables three-dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain. Methods Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope. Results We found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin-fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue. Conclusions The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies. [ABSTRACT FROM AUTHOR]

Background Adult studies indicate a role for ghrelin in functional dyspepsia ( FD) mediated through ghrelin's effect on gastric emptying ( GE). This study examines the relationship between ghrelin, liquid GE, and pain in children with FD. Methods Thirteen FD patients reporting symptoms consistent with post-prandial distress syndrome ( PDS) and 17 healthy controls were enrolled. All participants received a liquid meal containing 13C-sodium acetate. Pain severity, liquid GE utilizing exhaled 13CO2 from the sodium acetate breath tests ( ABT), plasma acyl ghrelin ( AG), and des-acyl ghrelin concentrations were measured at specific intervals over 240 min following ingestion. Key Results FD- PDS patients demonstrated lower mean baseline AG (14.8 ± 9.7 vs 27.2 ± 14.0 fmol/mL; p = 0.013), AG Cmax (24.6 ± 8.2 vs 40.5 ± 16.8 fmol/mL; p = 0.007), and AG flux (18.2 ± 7.8 vs 32.7 ± 17.3 fmol/mL; p = 0.015) than controls. The time to reach maximum exhaled 13CO2 concentration (T max) was longer in FD patients than controls (47.5 ± 18.5 vs 35.8 ± 11.8 min; p = 0.046). Significant relationships between ghrelin analyte ratios and ABT parameters were largely confined to control participants. Conclusions & Inferences FD- PDS in children is associated with lower fasting and maximum AG concentrations, and dampened AG flux. These data suggest a possible role for altered ghrelin physiology in the pathogenesis of PDS. [ABSTRACT FROM AUTHOR]

BackgroundAbnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.MethodUsing high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.ResultsCases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.ConclusionThe results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. [ABSTRACT FROM PUBLISHER]

Objective: To analyse the natural history and survival of corticobasal degeneration by investigating the clinical features of 14 cases confirmed by postmortem examination.Methods: Patients with definite corticobasal degeneration were selected from the research and clinical files of seven tertiary medical centres in Austria, the United Kingdom, and the United States. Clinical features were analysed in detail.Results: The sample consisted of eight female and six male patients; mean age at symptom onset was 63 (SD 7.7) years, and mean disease duration was 7.9 (SD 2.6) years. The most commonly reported symptom at onset included asymmetric limb clumsiness with or without rigidity (50%) or tremor (21%). At the first neurological visit, on average 3.0 (SD 1.9) years after symptom onset, the most often encountered extrapyramidal features included unilateral limb rigidity (79%) or bradykinesia (71%), postural imbalance (45%), and unilateral limb dystonia (43%). Ideomotor apraxia (64%), and to a lesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy. Median survival time after onset of symptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival.Conclusion: The results confirm that unilateral parkinsonism unresponsive to levodopa and limb ideomotor apraxia are the clinical hallmarks of corticobasal degeneration, and only a minority of patients with corticobasal degeneration present with dementia. The study also suggests that a focal cognitive and extrapyramidal motor syndrome is indicative of corticobasal degeneration. Survival in corticobasal degeneration was shortened by the early presence of (more) widespread parkinsonian features or frontal lobe syndrome. [ABSTRACT FROM AUTHOR]

The advent of reduced intensity conditioning (RIC) regimens has permitted the extension of allo-SCT to selected patients into their eighth decade but GVHD remains a major cause of morbidity and mortality. Alemtuzumab is increasingly used to reduce the risk of severe GVHD, but there are concerns that T-cell depletion may compromise outcome particularly in older patients. We therefore studied the impact of pre-transplant factors on the outcome of 187 patients with a haematological malignancy over the age of 60 transplanted using an alemtuzumab-based RIC regimen of whom co-morbidity scoring was possible in 169. Of the patients, 120 had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 1 and 49 had a score of 2 or more. The 5-year OS was 33%. In multivariable analysis, OS was determined by co-morbidity score (P=0.001) and disease status at transplant (P=0.004) but not by patient age. Non-relapse mortality was determined by co-morbidity score (P=0.001). Two-year OS for patients with a HCT-CI of 0-1 was 59 versus 6% for patients with a higher score. Alemtuzumab-based RIC allografts can be delivered safely in patients aged over 60 but co-morbidity scoring is mandatory to identify patients who will benefit. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic, disabling neuropsychiatric disorder characterised by positive, negative and cognitive symptoms. The aetiology is not known, although genetic, imaging and pathological studies have implicated both neurodevelopmental and neurodegenerative processes. The substantia nigra is a basal ganglia nucleus responsible for the production of dopamine and projection of dopaminergic neurons to the striatum. The substantia nigra is implicated in schizophrenia as dopamine has been heavily implicated in the dopamine hypothesis of schizophrenia and the prevalent psychotic symptoms and the monoamine theory of depression, and is a target for the development of new therapies. Studies into the major dopamine delivery pathways in the brain will therefore provide a strong base in improving knowledge of these psychiatric disorders. This post-mortem study examines the cytoarchitecture of dopaminergic neurons of the substantia nigra in schizophrenia ( n = 12) and depression ( n = 13) compared to matched controls ( n = 13). Measures of nucleolar volume, nuclear length and nuclear area were taken in patients with chronic schizophrenia and major depressive disorder against matched controls. Astrocyte density was decreased in schizophrenia compared to controls ( p = 0.030), with no change in oligodendrocyte density observed. Significantly increased nuclear cross-sectional area ( p = 0.017) and length ( p = 0.021), and increased nucleolar volume ( p = 0.037) in dopaminergic neurons were observed in schizophrenia patients compared with controls, suggesting nuclear pleomorphic changes. No changes were observed in depression cases compared to control group. These changes may reflect pathological alterations in gene expression, neuronal structure and function in schizophrenia. [ABSTRACT FROM AUTHOR]

Anti-cholinergic drugs are used in the treatment of Parkinson's disease (PD) and they can improve motor disability in some patients and may alter the expression of dyskinesia. We report the effects of anti-cholinergic and pro-cholinergic agents administered alone and combined with l-DOPA, on motor function in 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. Administration of atropine to MPTP-treated marmosets, not previously exposed to l-DOPA, improved motor disability but this did not occur with other centrally acting anti-cholinergics. Motor disability was worsened by centrally acting pro-cholinergics. However, neither peripherally acting anti- nor pro-cholinergics produced any effect on motor disability or dyskinesia. In MPTP-treated marmosets previously primed with l-DOPA to exhibit dyskinesia, acute l-DOPA challenge induced both chorea and dystonia. In these animals, centrally acting anti-cholinergics including atropine and trihexyphenidyl reversed motor deficits, but induced chorea. Combined with l-DOPA, both centrally and peripherally acting anti-cholinergics reduced peak locomotor activity and produced more chorea than dystonia compared to l-DOPA alone. Centrally acting pro-cholinergics decreased locomotor activity, worsened motor disability and induced dystonia. Co-administered with l-DOPA, pro-cholinergics reduced locomotor activity and decreased chorea while increasing dystonia compared with l-DOPA alone. In conclusion, anti-cholinergics can increase chorea with and without l-DOPA but improve motor disability. Pro-cholinergics decrease the proportion of chorea when combined with l-DOPA, increase motor disability and antagonise l-DOPA's effectiveness. These data suggest that there may be a case for revisiting the use of anti-cholinergic drugs in the treatment of PD. [ABSTRACT FROM AUTHOR]

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients. [ABSTRACT FROM AUTHOR]

Vertically-aligned carbon nanofibres (VACNFs) have been synthesized in a mixture of acetone and air using catalytic DC plasma-enhanced chemical vapour deposition. Typically, ammonia or hydrogen is used as an etchant gas in the mixture to remove carbon that otherwise passivates the catalyst surface and impedes growth. Our demonstration of the use of air as the etchant gas opens up the possibility that ion etching could be sufficient to maintain the catalytic activity state during synthesis. It also demonstrates a path toward growing VACNFs in the open atmosphere. [ABSTRACT FROM AUTHOR]

Aims Abnormal sleep is a common feature of Parkinson's disease ( PD) and prodromal disorders of sleep are frequent (e.g. restless legs syndrome and rapid eye movement sleep behaviour disorder). However, the exact pathological basis of disturbed sleep remains as yet undefined. Methods To investigate this further, 32 PD cases were stratified into three groups: (1) PD with disturbed sleep, PD( S); (2) PD with dementia ( PDD) and disturbed sleep, PDD( S); and (3) PD without disturbed sleep, PD(nS). The extent of α-synuclein (α Syn) and Alzheimer disease ( AD)-type pathology [amyloid β peptide ( Aβ) and tau] was assessed in 15 regions of the PD brain. Results The results demonstrate a significant association between disturbed sleep in PD and α Syn pathology in specific brainstem [locus coeruleus ( P = 0.006) and raphe nuclei ( P = 0.02)], hypothalamic [paramammillary nuclei ( P = 0.04) and posterior nucleus ( P = 0.02)], subcortical/limbic [amygdala ( P = 0.03), thalamus ( P = 0.01)] and cortical [entorhinal cortex ( P = 0.01)] regions. A statistically significant increase of tau pathology was observed in the amygdala ( P = 0.03), CA2 sector of the hippocampus ( P = 0.01) and entorhinal cortex ( P = 0.04) in PD cases with disturbed sleep. Conclusions Pathological changes in these structures, residing in the brain circuitry relating to sleep physiology, strongly predict the presence of sleep disturbances in PD. [ABSTRACT FROM AUTHOR]

The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41-60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups ( p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density ( p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction. [ABSTRACT FROM AUTHOR]

Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR)=0.42, P=0.008 and HR=0.45, P=0.012, respectively). Two-year TRM was 29%: higher with younger age (HR=0.97/year, P=0.041), female recipient (HR=2.55, P=0.049) and increasing grade of acute GVHD (HR=1.87, P=0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR=0.62 per increasing grade, P=0.035 and HR=0.52, P=0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect. [ABSTRACT FROM AUTHOR]

Decreased cortical thickness and reduced activity as measured by fMRI in the grey matter of the subgenual cingulate cortex have been reported in schizophrenia and bipolar disorder, and cortical grey matter loss has been reliably reported in the frontal and temporal lobes in schizophrenia. The aim of this study was to examine the thickness of each of the six cortical layers in the subgenual cingulate cortex, five frontal lobe and four temporal lobe gyri. We examined two separate cohorts. Cohort 1 examines the subgenual cingulate cortex (SCC) in schizophrenia ( n = 10), bipolar disorder ( n = 15) and major depressive disorder ( n = 20) against control subjects ( n = 19). Cohort two examines frontal and temporal gyri in schizophrenia ( n = 16), major depressive disorder ( n = 6) against matched controls ( n = 32). The cohorts were selected with identical clinical criteria, but underwent different tissue processing to contrast the effect of chemical treatment on tissue shrinkage. Measurements of layer I-VI thickness were taken from cresyl-violet- and haematoxylin-stained sections in cohort one and from cresyl-violet- and H&E-stained sections in cohort two. SCC cortical thickness decreased in male subjects with bipolar disorder ( p = 0.048), and male schizophrenia cases showed a specific decrease in the absolute thickness of layer V ( p = 0.003). Compared to controls, the relative thickness of layer V in the crown of the SCC decreased in schizophrenia ( p < 0.001). A significant decrease in total cortical thickness was observed across the frontal lobe in schizophrenia ( p < 0.0001), with specific pyramidal layer thinning in layers III ( p = 0.0001) and V ( p = 0.005). There was no effect of lateralization. No changes were noted in temporal lobe cortical thickness. This study demonstrates diminished pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Multimarker quantitative real-time polymerase chain reaction (qRT-PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. Objectives To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy. Methods Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3 years and 9 months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0-II, n = 154) and metastatic melanoma (late stages, III-IV, n = 76). Each specimen was examined by qRT-PCR analysis for the expression of five markers: MLANA, ABCB5, TGFβ2, PAX3d and MCAM. Results In total, 212 of the patients with melanoma (92%) expressed markers in their peripheral blood. Two markers, MLANA and ABCB5, had the greatest prognostic value, and were identified as statistically significant among patients who experienced disease recurrence within our study period, being expressed in 45% (MLANA) and 49% (ABCB5) of patients with recurrence ( P = 0·001 and P = 0·031, respectively). For patients administered nonsurgical treatments, MCAM expression correlated with poor treatment outcome. Conclusions Circulating tumour cells were detectable at all stages of disease and long after surgical treatment, even when patients were considered disease free. Specifically, expression of ABCB5 and MLANA had significant prognostic value in inferring disease recurrence, while MCAM expression was associated with poor patient outcome after treatment, confirming multimarker qRT-PCR as a potential technique for monitoring disease status. [ABSTRACT FROM AUTHOR]

Osteoporosis and associated fragility fractures are an increasing problem across the developed world. The elderly osteoporotic acetabular fracture presents a difficult problem due to high failure rates and poor outcomes. Standard management may or may not include fracture fixation, but generally includes a period of protected weight bearing, even if total hip replacement has been performed. We present a series of 12 cases of complex osteoporotic acetabular fractures in elderly patients, managed successfully using primary fracture fixation and total hip replacement with trabecular metal technology. Immediate weight bearing was allowed in all cases, few complications have been seen, and no component migration has been identified in any case. [ABSTRACT FROM AUTHOR]

ABSTRACT We evaluated invasive exotic weeds and plant species diversity in relation to depth to groundwater (DTW) and microtopography in areas with DTW from 0·3-4 m in Owens Valley, California. Transects dominated by common plant species of the area were read at 1-cm intervals, and species cover was obtained at different scales: 1-m transect portions (microsites), whole transects (68 m average length), and the whole study area. Species richness and the Shannon-Wiener diversity index were obtained in microsites. DTW and microtopographical variation (soil-surface relative elevations) were jointly measured along the vegetation transects. Found in 34% of the sampled transects, the annual Bassia hyssopifolia was the most common exotic weed of the area. Its cover in the whole study area was only 0·9%, but it was the second most dominant species (19% cover) in microsites. B. hyssopifolia coexisted mainly with herbaceous species, typically in places with shallow groundwater (average <1·5 m) and microtopographical depressions. However, B. hyssopifolia cover was not affected by variations in DTW or relative elevation. In contrast, B. hyssopifolia cover was negatively associated with perennial cover and species richness. Species diversity (Shannon-Wiener) slightly decreased with the increase in DTW but not with changes in microtopography. In contrast, species richness clearly varied with the identity of the dominant species in microsites. Our study suggests that the variation in community-intrinsic factors such as competition and diversity may play a greater role in the growth of invasive plants than the variation in physical factors such as groundwater and microtopography. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study was designed to better define the nature of the relationship among vegetation, groundwater level and microtopography in an arid area where depth to groundwater (DTW) was 0-4 m. Plant cover, DTW and relative elevations were jointly measured along 67 vegetation transects throughout the Owens Valley, CA, USA. These transects were dominated by major species of the area: Artemisia tridentata, Atriplex torreyi, Ericameria nauseosa, Distichlis spicata, Juncus arcticus, Leymus triticoides, Sarcobatus vermiculatus and Sporobolus airoides. Plant species occurrence was associated with different DTW. J. arcticus and D. spicata occurred more frequently in areas with the shallowest groundwater (<1·5 m). A. torreyi, L. triticoides and E. nauseosa dominated areas with intermediate DTW (1·5-2·0 m); whereas S. airoides, S. vermiculatus and A. tridentata dominated areas with deeper water tables (>2·0 m). Species were also linked to different microtopographic positions: L. triticoides and J. arcticus were mainly restricted to depressions whereas A. torreyi and A. tridentata were widely distributed in higher positions on the microtopographical gradient. Only 6% of the variation in vegetation cover was accounted for by DTW throughout the study area ( N = 820). Cover of individual species was usually unaffected by DTW variation. Results suggest that species distribution is linked to groundwater conditions, but cover of vegetation is only partially affected by DTW variation. This is possible because water tables in our study area are within the rooting depth of most species and plants appear to be well adapted to shallow DTW variations. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: The incidence of deep vein thrombosis, non-fatal pulmonary embolism and fatal pulmonary embolism may be as high as 61%, 10% and 2%, respectively, in patients with pelvic and acetabular injuries. A survey of the pelvic and acetabular units across the United Kingdom was performed to ascertain the thrombo-prophylaxis policy for these patients. In particular, questions were asked about different regimes on post-operative patients, conservatively managed patients and those simply discussed over the telephone. We enquired about their known rates of DVT and PE and their methods of data collection.Methods: Postal questionnaires were sent to 22 pelvic and acetabular trauma centres around the United Kingdom.Results: Replies from 18 units were received in which a total of 837 operations are performed per year. Forty-five percent of pelvic and acetabular units do not routinely prescribe chemical prophylaxis for post-operative patients and 56% do not prescribe prophylaxis for conservatively managed patients. The policy of the remaining units showed no consistency in duration or agent. Fifty-three percent of units use a database to collect information related to the numbers of patients operated up on. Forty-seven percent have no defined method for collecting DVT and PE numbers. For this reason, reported rates of proximal DVT, non-fatal PE and fatal PE were below that expected at 2.5%, 0.8% and 0.1%, respectively.Conclusions: Despite high rates of thrombo-embolic complications in patients with pelvic and acetabular injuries there is no UK consensus on prescribing prophylaxis. [ABSTRACT FROM AUTHOR]

The clinical course of 2009 H1N1 influenza in Allo-SCT patients is unknown. Data were collected in the UK from October 2009 to April 2010 on laboratory-confirmed cases of H1N1 influenza in Allo-SCT recipients. H1N1 infection was diagnosed in 60 patients, median age 42 years, at a median of 10 months post-SCT. Twenty-one patients (35%) developed pneumonia and nine (15%) required admission to intensive care units. Actuarial mortality was 7% at 28 days and 19% 4 months post-diagnosis of 2009 H1N1 influenza. Increasing age and pre-existing lung disease were risk factors for pneumonia (P=0.006 and 0.037, respectively); older age was a risk factor for death (P=0.012). Morbidity and mortality from 2009 H1N1 influenza in SCT patients exceeds that of immunocompetent patients, but parallels that in other critically ill hospitalised cohorts; the elderly and those with chronic pulmonary disease are at greatest risk. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Heminephroureterectomy (HN) is our treatment of choice in a duplex system with non-functioning moiety. We examined the need for endoscopic incision (EI)/bladder reconstructive surgery (BRS) and whether ureteroceles and/or vesicoureteric reflux (VUR) influenced management options.Methods: Retrospective study of patients undergoing HN by a single surgeon (2003-2008). Patients were classified according to the presence (Group 1) or absence (Group 2) of ureterocele. The groups were subdivided with coexisting dilating VUR (a) or not (b). Statistical analysis included Fisher's exact test.Results: Thirty-one children were identified. Seventeen (54.8%) had ureterocele (Group 1) and 14 patients had no ureterocele (Group 2). Group 1 had eight with VUR (1a) and nine without (1b). Group 2 had seven with VUR (2a) and seven without (2b). Significantly more patients with ureterocele required EI/BRS (p = 0.006). Five (29%) in Group 1 required BRS versus none in Group 2 (p = 0.04). Six (75%) in Group 1a underwent EI/BRS versus three (33%) in Group 1b (p = 0.15). Significantly more in Group 1a required EI prior to HN versus Group 1b (p = 0.04). Similar numbers of patients required BRS in Groups 1a and 1b (p = 0.61).Conclusions: In the absence of ureterocele, there is minimal likelihood of requiring surgery apart from HN, independent of VUR. Presence of ureterocele is an indicator for additional procedure within the bladder. There is a higher incidence of EI when ureterocele co-exists with dilating VUR. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: We present data from a single surgeon experience of paediatric transperitoneal (TP) and retroperitoneal (RP) minimally invasive approaches for partial (PN) and total nephrectomy (TN).Methods: A retrospective review was conducted in the patients undergoing nephrectomy between 2003 and 2008. Patients were divided depending on PN or TN and the approach (RP or TP). Primary outcome was the need to convert to an open procedure. Secondary outcomes included operation time, length of stay (LOS) and complications. Statistical analysis included Fisher's exact test.Results: 68 patients underwent minimally invasive TN/PN, 49 (72%) RP versus 19 (28%) TP. There were no differences between the groups in terms of sex, age, pathology, LOS, complication rate and conversion rate. Neither group recorded mortality. Conversion occurred because of difficult anatomy or the kidney size rather than an adverse event. Overall, there was no difference in operative time between the RP and TP. This was also the case for TN only. However, the PN subgroup demonstrated a decreased operative time with RP (p = 0.049) possibly due to better anatomical delineation. There were no complications.Conclusions: Minimally invasive TN or PN can be performed via retroperitoneal or transperitoneal routes with minimal morbidity. With training, PN via retroperitoneal approach can be achieved with significantly reduced operative time. [ABSTRACT FROM AUTHOR]

Auto-SCT is the standard first-line consolidative therapy in patients with multiple myeloma (MM). We performed a national benchmarking outcome analysis for patients with MM who underwent a single auto-SCT in 1999 and 2005. They were identified from the British Society of Blood and Marrow Transplantation (BSBMT) (n=211 and n=453) and EBMT (n=1311 and n=1978) registries. An improvement in Day+100 and D+365 non-relapsed mortality (NRM) was shown between years 1999 and 2005 (P=0.0495). The 4-year relapse rate (RR) was significantly higher in 2005 (P=0.0003) and was associated with a shorter time to next treatment (TTNT) (P=0.025). The 4-year PFS was significantly lower in 2005 (P=0.0012), with the year of auto-SCT (P=0.001) and status at auto-SCT (P=0.02) being independently significant. The 4-year OS was similar between the year cohorts (P=0.266). In the 'benchmarking' comparison, the European Group for Blood and Marrow Transplantation (EBMT) 1999 cohort demonstrated the best PFS, although no year-of-transplant effect could be demonstrated on the 4-year OS rates (P=0.760). An improvement in supportive care resulting in reduced NRM is evident between the decades. The main cause of treatment failure remains disease progression. The similarity in OS between the years may reflect the introduction of novel agents in salvage therapy. The reduced PFS in 2005 is as yet not fully explained, but may represent recent disease response criterion standardization. [ABSTRACT FROM AUTHOR]

Young children are at increased risk for valproic acid (VPA) hepatotoxicity. Urinary organic acid profiles, as a surrogate of mitochondrial function, were obtained in children 1.9 to 17.3 years of age (n = 52) who were undergoing treatment with VPA for seizure disorders. Age-matched patients receiving treatment with carbamazepine (CBZ; n = 50) and healthy children not undergoing treatment (n = 22) served as controls. Age-related changes in organic acid profiles were observed in all three groups. Although the untreated and CBZ control groups were indistinguishable from each other with respect to the principal-component analysis (PCA) score plots of the subjects, a distinct boundary was apparent between the VPA and each of the control groups. Interindividual variability was observed in the VPA-induced alterations in endogenous pathways corresponding to branched-chain amino acid metabolism and oxidative stress. The data suggest that more detailed metabolomic analysis may provide novel insights into biological mechanisms and predictive biomarkers for children at highest risk for serious toxicity. [ABSTRACT FROM AUTHOR]

The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment. [ABSTRACT FROM AUTHOR]

Fifty-one patients with primary myelofibrosis (PMF) received allogeneic haematopoietic stem cell transplants from related (n=33) or unrelated (n=18) donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative regimens including CY plus BU (n=4) or TBI (n=23). Twenty-four patients, 40-64 years old, received reduced-intensity conditioning (RIC) regimens. All RIC regimens contained fludarabine, combined with melphalan (n=19) or BU (n=5), and alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n=19). Four patients (17%) in the RIC group had primary graft failure. Previous splenectomy reduced time to engraftment in the RIC group (13 versus 20 days; P=0.008). For MA and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31% (P=0.67), progression-free survival 44 and 24% (P=0.87), and actuarial relapse rates 15 and 46% (P=0.06). Non-relapse mortality at 3 years was 41% for the myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of patients in the myeloablative and RIC groups, respectively. Extensive chronic GVHD developed in 30 and 35% of evaluable patients, respectively. [ABSTRACT FROM AUTHOR]

Disruptions on ITER present challenges to handle the intense heat flux, the large forces from halo currents, and the potential first wall damage from energetic runaway electrons. Injecting large quantities of material into the plasma during the disruption can reduce the plasma energy and increase its resistivity to mitigate these effects. Assessments of the amount of various mixtures and quantities of the material required have been made to provide collision mitigation of runaway-electron conversion, which is the most difficult challenge. The quantities of the material required (∼0.5 MPa ∙ m³ for deuterium or helium gas) are large enough to have implications on the design and operation of the vacuum system and tokamak exhaust processing system. [ABSTRACT FROM AUTHOR]

The article offers efficient ways for safe referral and transfer of paitents to trauma centers in Great Britain. It notes that the initial management, planning the referral to major trauma center, and informing the tertiary center are some of the processes included in the management of trauma patients. A diagram is also presented depicting the flow of interpersonal transfer.