TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.

Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.

Morphological Brain Changes after Climbing to Extreme Altitudes-A Prospective Cohort Study.

BACKGROUND Findings of cerebral cortical atrophy, white matter lesions and microhemorrhages have been reported in high-altitude climbers. The aim of this study was to evaluate structural cerebral changes in a large cohort of climbers after an ascent to extreme altitudes and to correlate these findings with the severity of hypoxia and neurological signs during the climb. METHODS Magnetic resonance imaging (MRI) studies were performed in 38 mountaineers before and after participating in a high altitude (7126m) climbing expedition. The imaging studies were assessed for occurrence of new WM hyperintensities and microhemorrhages. Changes of partial volume estimates of cerebrospinal fluid, grey matter, and white matter were evaluated by voxel-based morphometry. Arterial oxygen saturation and acute mountain sickness scores were recorded daily during the climb. RESULTS On post-expedition imaging no new white matter hyperintensities were observed. Compared to baseline testing, we observed a significant cerebrospinal fluid fraction increase (0.34% [95% CI 0.10-0.58], p = 0.006) and a white matter fraction reduction (-0.18% [95% CI -0.32--0.04], p = 0.012), whereas the grey matter fraction remained stable (0.16% [95% CI -0.46-0.13], p = 0.278). Post-expedition imaging revealed new microhemorrhages in 3 of 15 climbers reaching an altitude of over 7000m. Affected climbers had significantly lower oxygen saturation values but not higher acute mountain sickness scores than climbers without microhemorrhages. CONCLUSIONS A single sojourn to extreme altitudes is not associated with development of focal white matter hyperintensities and grey matter atrophy but leads to a decrease in brain white matter fraction. Microhemorrhages indicative of substantial blood-brain barrier disruption occur in a significant number of climbers attaining extreme altitudes.

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

Betula pendula, Betula pubescens and other birches in Europe: distribution, habitat, usage and threats

Silver birch (Betula pendula Roth) and downy birch (Betula pubescens Ehrh.) are short-lived, relatively small broadleaved trees that occur throughout most of Europe, particularly in northern regions. In southern Europe, birch trees are confined to mountainous areas, as they do not tolerate prolonged summer drought. Birch has a light canopy of small serrated leaves, and characteristic smooth, white to grey bark. In northern regions, birch trees can dominate the landscape up to the tree-line, whereas in the centre of their range they often occur early in secondary succession because of their abundant seed production, low demands on soil quality, and intolerance of shade. Birch trees provide the predominant hard wood source in northern Europe, and some varieties of Betula pendula produce highly priced veneers, while Betula pubescens is mostly used for pulp and fire wood. Other rarer species of birch are endemic to Europe contributing to the continental biodiversity even at high elevations and latitudes.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Myelination of the right parahippocampal cingulum is associated with physical activity in young healthy adults.

Recent evidence suggests that individual differences in physical activity (PA) may be associated with individual differences in white matter microstructure and with grey matter volume of the hippocampus. Therefore, this study investigated the association between PA and white matter microstructure of pathways connecting to the hippocampus. A total of 33 young, healthy adults underwent magnetic resonance imaging (MRI). High angular resolution diffusion-weighted imaging and multi-component relaxometry MRI scans (multi-component driven equilibrium pulse observation of T1 and T2) were acquired for each participant. Activity levels (AL) of participants were calculated from 72-h actigraphy recordings. Tractography using the damped Richardson Lucy algorithm was used to reconstruct the fornix and bilateral parahippocampal cinguli (PHC). The mean fractional anisotropy (FA) and the myelin water fraction (MWF), a putative marker of myelination, were determined for each pathway. A positive correlation between both AL and FA and between AL and MWF were hypothesized for the three pathways. There was a selective positive correlation between AL and MWF in the right PHC (r = 0.482, p = 0.007). Thus, our results provide initial in vivo evidence for an association between myelination of the right PHC and PA in young healthy adults. Our results suggest that MWF may not only be more specific, but also more sensitive than FA to detect white matter microstructural alterations. If PA was to induce structural plasticity of the right PHC this may contribute to reverse structural alterations of the right PHC in neuropsychiatric disorder with hippocampal pathologies.

Polynesian mythology and ancient traditional history of the New Zealand race as furnished by their priests and chiefs

by Sir George Grey, late governor-in-chief in New Zealand

Exploring the use of pharmaceutical patient assistance programs as an option to improve access to and affordability of prescription drugs

Background. Pharmaceutical-sponsored patient assistance programs (PAPs) are charity programs that provide free or reduced-priced medications to eligible patients. PAPs have the potential to improve prescription drug accessibility for patients but currently there is limited information about their use and effectiveness. ^ Objectives and methods. This dissertation described the use of PAPs in the U.S. through the conduct of two studies: (1) a systematic review of primary studies of PAPs from commercially-published and “grey” literature sources; and (2) a retrospective, cross-sectional study of cancer patients' use of PAPs at a tertiary care cancer outpatient center. ^ Results. (1) The systematic review identified 33 studies: 15 evaluated the impact of PAP enrollment assistance programs on patient healthcare outcomes; 7 assessed institutional costs of providing enrollment assistance; 7 surveyed stakeholders; 4 examined other aspects. Standardized mean differences calculated for disease indicator outcomes (most of which were single group, pre-posttest designs) showed significant decreases in glycemic and lipid control, and inconsistent results for blood pressure. Grey literature abstracts reported insufficient statistics for calculations. Study heterogeneity made weighted summary estimates inappropriate. Economic analyses indicated positive financial benefits to institutions providing enrollment assistance (cost) compared to the wholesale value of the medications provided (benefit); analyses did not value health outcomes. Mean quality of reporting scores were higher for observational studies in commercially-published articles versus full text, grey literature reports. (2) The cross-sectional study found that PAP outpatients were significantly more likely to be uninsured, indigent, and < 65 years old than non-PAP patients. Nearly all non-PAP and PAP prescriptions were for non-cancer conditions, either for co-morbidities (e.g., hypertension) or the management of treatment side effects (e.g., pain). Oral chemotherapies from PAPs were significantly more likely to be for breast versus other cancers, and be a newer, targeted versus traditional chemotherapy.^ Conclusions. In outpatient settings, PAP enrollment assistance plus additional medication services (e.g., counseling, reminders, and free samples) is associated with improved disease indicators for patients. Healthcare institutions, including cancer centers, can offset financial losses from uncompensated drug costs and recoup costs invested in enrollment assistance programs by procuring free PAP medications. Cancer patients who are indigent and uninsured may be able to access more outpatient medications for their supportive care needs through PAPs, than for cancer treatment options like oral chemotherapies. Because of the selective availability of drugs through PAPs, there may be more options for newer, oral, targeted chemotherapies for the treatment breast cancer versus other for other cancers.^

Mineral resources in Lower Brule Indian Reservation

On the Lower Brule Indian Reservation in South Dakota, about 3 million tons of metallic manganese are in low-grade deposits in the DeGrey Member of the Pierre Shale on the reservation. The geology and methods of mining and processing this sub-economic mineral resource have been studied extensively; technologically, extraction of manganese is possible. However, an efficient, economical method to separate manganese-bearing nodules from the shale host rocks has yet to be found. The manganiferous nodules occur in the Oacoma zone of the Sully shale member (De-Grey Member) which is a subdivision of the South Dakota Pierre Shale formation. These nodular deposits have an interesting similarity in stratigraphical position, lithology and manganese content to those of the Porcupine Mountain area in Manitoba.

Geochemistry of basement clasts from sediment core CRP-3 in the ross Sea, Antarctica

Distribution patterns and petrographical and mineral chemistry data are described for the most representative basement lithologies occuring as clast in the c. 824 m thick Tertiary sedimentary sequence at the CRP-3 drillsite. These are granule to bolder grain size clasts of igneous and metamorphic rocks. Within the basement clast assemblage, granitoid pebbles are the predominant lithology. They consist of dominant grey biotic-bearing monzogranite, pink biotite-hornblende monzogranite, and biotite-bearing leucomomonzgranite. Minor lithologies include: actinolite-bearing leucotonalite, microgranite, biotite-hornblende quartz-monzonitic porphyr, and foliated biotic leucomonzogranite. Metamorphic clasts include rocks of both granitic and sedimentary derivation. They include mylonitic biotic orthogneiss, with or without garnet, muscovite-bearing quartzite, sillimanite-biotite paragneiss, biotite meta-sandstone, biotite-spotted schist, biotite-clacite-clinoamphibole meta-feldspathic arenite, biotite-calcite-clinozoisite meta-siltstone, biotite±clinoamphibole meta-marl, and graphite-bearing marble. As in previous CRP drillcores, the ubiquitous occurence of biotite±hornblende monzogranite pebbles is indicative of a local provenance, closely mirroring the dominance of these lithologies in the on-shore basement, where the Cambro-Ordovician Granite Harbour Intrusive Complex forms the most extensively exposed rock unit.

Sedimentology of cores from the continental rise west of the Antarctic Peninsula

The continental rise west of the Antarctic Peninsula includes a number of large sediment mounds interpreted as contourite drifts. Cores from six sediment drifts spanning some 650 km of the margin and 48 of latitude have been dated using chemical and isotopic tracers of palaeoproductivity and diatom biostratigraphy. Interglacial sedimentation rates range from 1.1 to 4.3 cm/ka. Glacial sedimentation rates range from 1.8 to 13.5 cm/ka, and decrease from proximal to distal sites on each drift. Late Quaternary sedimentation was cyclic, with brown, biogenic, burrowed mud containing ice-rafted debris (IRD) in interglacials and grey, barren, laminated mud in glacials. Foraminiferal intervals occur in interglacial stages 5 and 7 but not in the Holocene. Processes of terrigenous sediment supply during glacial stages differed; meltwater plumes were more important in stages 2-4, turbidity currents and ice-rafting in stage 6. The terrigenous component shows compositional changes along the margin, more marked in glacials. The major oxides Al2O3 and K2O are higher in the southwest, and CaO and TiO2 higher in the northeast. There is more smectite among the clay minerals in the northeast. Magnetic susceptibility varies along and between drifts. These changes reflect source variations along the margin. Interglacial sediments show less clear trends, and their IRD was derived from a wider area. Downslope processes were dominant in glacials, but alongslope processes may have attained equal importance in interglacials. The area contrasts with the East Antarctic continental slope in the SE Weddell Sea, where ice-rafting is the dominant process and where interglacial sedimentation rates are much higher than glacial. The differences in glacial setting and margin physiography can account for these contrasts.

Investigation of manganese nodules from the Southern Tasman Sea

Two manganese nodules having a high clay content, a low Mn/Fe ratio, and low contents of valuable metals (Ni 0.25%, Cu 0.17%, Co 0.06%) were recovered in a grab sample during a short geological cruise in HMAS Kimbla in the southern Tasman Sea in May 1979. Five stations were occupied. Free-fall grabs recovered sediment or pumice from four stations; nothing was recovered from the fifth. The carbonate compensation depth in the region is about 4500 m. Reddish brown clay, but no manganese nodules, was recovered in the central southern Tasman Sea, from depths of 4900-5100 m. The nodules, together with grey calcareous mud, were obtained from a depth of 4300 m, farther to the northwest, near Gascoyne Seamount (250 n. miles SE of Sydney). The results suggest nodules with high metal values are likely to exist only in the broad and deep depression in the central southern Tasman Sea southeast of Gascoyne Seamount, where sedimentation rates are low and oxidising conditions prevail. Whether nodule fields are present or not will only be resolved by considerably more sampling.

Geochemical data and mineralogical properties of bulk sediment composition of ODP Hole 195-1202B

During Leg 195 of the Ocean Drilling Program, Site 1202 was drilled in the subtropical northwestern Pacific Ocean beneath the Kuroshio (Black Current) between northern Taiwan and the Ryukyu Island Arc on the northern flank of the I-Lan Ridge at 1274 m water depth. The upper 110 m of the Site 1202 section, composed of dark grey calcareous silty clay, provide an expanded record of environmental changes during the last 28 kyr. The sediments were deposited at high sedimentation rates between 3.0 and 5.0 m/kyr and peak values of 9.0 m/kyr between 15.1 and 11.2 ka BP. Variations in the modes and sources of detrital sediment input, as inferred from sediment granulometry, mineralogy, and elemental XRF-scanner data, reflect changes in environmental boundary conditions related to sea-level changes, Kuroshio variability, and the climate-driven modes of fluvial runoff. The provenance data point to increased sediment supply from northwestern Taiwan between 28 and 19.5 ka BP and from East China sources between 19.5 and 11.2 ka BP. The change in provenance at 19.5 ka BP reflects increased fluvial runoff from the Yangtze River and strong sediment reworking from the East China Sea shelf in the course of increased humidity and postglacial sea-level rise, particularly after 15.1 ka BP. The Holocene was dominated by sediments that originated from rivers in northeastern Taiwan. For the pre-Holocene period prior to 11.2 ka BP, low portions of sortable silt (63-10 ?m) show that the Kuroshio did not enter the Okinawa Trough, because of low sea-level. In turn, high proportions of sortable silt and sediment provenance from northeastern Taiwan point to strong ocean circulation under the direct and persistent influence of the Kuroshio during the Holocene. The reentrance of the Kuroshio to the Okinawa Trough was heralded by two pulses in relative current strengthening at 11.2 and 9.5 ka BP, as documented by stepwise increases in sortable silt in the lower Holocene section. From a global perspective, environmental changes in the southern Okinawa Trough show affinities to climate change in the western Pacific warm pool with little influence of climate teleconnections from the North Atlantic realm, otherwise seen in many other marine and terrestrial palaeoclimate records from southeastern Asia.

El aborto inseguro en América Latina y el Caribe

En América Latina, la tasa es de 32 abortos por cada 1000 mujeres y el 95% de estos presentan riesgos para la vida y la Salud de la mujer. La tasa de aborto en Europa Occidental, donde la Interrupción Voluntaria del Embarazo es legal, es de tan solo 12 casos por cada 1000 mujeres. Su prohibición solo alienta al aborto clandestino y en condiciones de riesgo. Idea y realización: Pieter Van Eecke Concepto y producción: Objeto Directo Diseño gráfico: Florencia Lastreto Fotografía: Natalie Mikhaloff y Médicos del Mundo Voz en off español: Jorge Varela Cámara: Pieter Van Eecke Animaciones: Florencia Lastreto Musica (Creative Commons Licence - Attribution - Non Commercial - Share alike) Bonifrate - Estudio Rural Em R Major Fabrizio Paternili - Profondo Blu Robin Grey - Ninety Days Instrumental Robin Grey – Every Walking Hour Instrumental Médicos del Mundo Francia Coordinadora General Uruguay: Carine Thibaut Comunicación: Mauricio de los Santos Agradecimientos: MYSU, Lilián Abracinskas, Morgane Aveline, Camila Giugliani, Jean Guerini, Sandrine Simon, Alain Forgeot, Aurore Voet.

Pollen record and lithology of a profile from Dumfriesshire, Scotland

Four samples, G5, G7, G8, and G10, collected by Dr W. W. Bishop from an exposed section in the bank of the River Annan, at Roberthill Farm, Dumfriesshire (S35, 110794) were submitted for pollen analysis (Table I.). The samples, with the exception of the uppermost, were from thin peat layers that lie in the middle of a series of water- laid sands, silts and clays several feet in thickness and now rather strongly arched. The lowermost sample, G5, was taken from an organic layer about | in. thick overlying fine sand and underlying some 2.5 in. of grey, silty fine sand. A narrow layer of sandy peat immediately above the silty, fine sand yielded sample G7, and G8 was collected from a similar peaty layer separated from G7 by more sandy- silty peat. The uppermost sample, G10, was taken from light grey clay 13 in. above sample G8.