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Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.
We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.
Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.
CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.
The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6–4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.
The Latino population in the United States is rapidly growing and faces profound health disparities; however, engagement of Latinos in biomedical research remains low. Our community-based participatory research partnership has recruited 2083 Spanish-speaking Latinos into 21 studies over 15 years. We sought to identify and describe the strategies we have used to successfully recruit and retain Spanish-speaking Latinos in research.
We abstracted and analyzed data from archived study notes, progress reports, team meeting minutes, and in-depth interviews conducted annually from community-based participatory research partnership members. We used a nominal group process to refine and prioritize strategies.
Overall, 13 recruitment strategies and 12 retention strategies emerged. These strategies relied on the creativity and perseverance of the study team and partners.
It is essential that we develop and disseminate effective recruitment and retention strategies that engage Latinos in biomedical research to reduce health disparities and promote health equity.
Introduction: The effectiveness of intravenous alteplase is highly time dependent, and very short door-to-needle times (DNT) of 30 minutes or less have been reported in single centre hospitals, but never in an entire population. QuICR (Quality Improvement and Clinical Research) Alberta Stroke Program aimed to reduce DNT to a median of 30 minutes across the Canadian province of Alberta. Methods: We used the Improvement Collaborative Methodology from early 2015 to September 2016 with participation from all 17 Stroke Centres in Alberta. This methodology included 4 face-to-face workshops, site visits, webinars, data collection, data feedback, intensive process mapping, and process improvements. We compared data in the pre-intervention period from 2009-2014 (collected during the Alberta Provincial Stroke Strategy) to data in the post-intervention period from March 2016-February 2017 (collected during the QuICR DTN Collaborative). Data from January 2015-February 2016 were excluded, as improvements were being implemented during this time. Results: There were a total of 2,322 treated cases in the pre- and post-intervention periods. The results show that the median DNT dropped from 68 minutes (n=1846) in the pre-intervention period to 36 minutes (n=476) in the post-intervention period (p<0.001). There were reductions in DNT across all hospital types: median DNT dropped from 63 to 32 minutes in Urban Tertiary Centres (p<0.001), from 73 to 32 minutes in Community with 24/7 neurology (p<0.001), from 85 to 62 minutes in Community with limited/no neurology (p<0.001), and from 74 to 52.5 minutes in rural centres (p<0.001). Conclusion: There were 21.5 to 41 minute reductions in median DNT across all hospital types including smaller rural and community hospitals. A targeted multi-site improvement collaborative can be an effective intervention to reduce DNT across an entire population.
We discuss efforts to explain the dust distribution, as it was derived from the F-coronal brightness, mainly how to explain a constant number density near the Sun. It is shown that silicate particles have temperatures below the blackbody temperature if the impurity from absorbing material amounts to less than 0.1% in volume. This effect is especially significant for porous particles and may explain why particles can approach to less than 3 R⊙ from the Sun. Another effect may arise from particles on high eccentricity orbits and from the influence of collisional fragments. Whereas on the one hand heat resistant silicate particles may cause a stable dust cloud in the solar vicinity, on the other hand dynamical effects may cause a variation of the number density in the corona in short time scales.
In recent years, the importance of fibre provision within the horse’s diet has been realised (Ralston 2005). Consideration of the evolutionary design of the animal, combined with a greater understanding of the aetiology of metabolic disorders, has re-iterated the need for horses to be fed diets high in fibre, especially those horses on maintenance rations. It has been acknowledged that although older horses can survive on maintenance rations, they are often at risk of weight loss (Ralston, 2005), a factor that is increased if dentition is poor (Dacre, 2005). Therefore nutritional management is vital to optimise nutrient provision. In dentally compromised animals, diet type and feed availability should be managed to promote ease of consumption, and subsequent factors compromising such consumption should be eliminated. Various methods of enhancing voluntary feed intake (VFI) have been devised (Dacre, 2005). Soaking hay may alleviate some problems associated with the ingestion and mastication of a course forage product, but can lead to consequences with decreased nutrient intake. Provision of softer fibre sources (haylage, silage) could also be considered, but will, conversely, increase nutrient intake. Short chopped fibre may decrease the overall need to chew. Other products, such as fibre pellets, may be fed soaked to horses with the most serious dental problems, thus removing the need for mastication. Currently there exists little information relating to VFI of various forage sources offered to older horses with compromised dentition. The aim of this study was to investigate dry matter intake (DMI), VFI and consumption rates of three fibre sources, hay (H), DM– 915g/kg, short-chop forage (SF), DM -860g/kg and soaked fibre pellets (FP), DM – 900g/kg, in veteran horses with poor dentition. SF and FP were both commercially available preparations consisting of high temperature dried grass and alfalfa (SF) and sugar beet and alfalfa (FP).
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
It has been known that non spherical silicate particles of a size comparable to the wavelength of light, and aggregates of such particles, produce negative polarization in the backscattering region (e.g. Xing & Hanner 1997, Yanamandra-Fisher & Hanner, 1999). It has now been shown that large aggregates of small absorbing particles of fractal dimension about 2 produce a slightly negative polarization at small phase angles (Levasseur-Regourd et al., 1997). The phase-curves strongly differ from those of Mie spheroidal particles. They are likely to be due to scattering by irregular dust particles and/or fluffy aggregates of numerous submicronic absorbing particles (Levasseur-Regourd et al., 1997; Lumme et al., 1997).
The observation of 8B solar Neutrinos in the Kamiokande-II detector is presented. Based on 450 days of data in the time period of January 1987 through May 1988, the measured flux obtained with Ee ≥ 9.3 MeV was 0.46 ± 0.13 (stat) ± 0.08 (sys) of the value predicted by the standard solar model. The detector and analysis methods were improved since June 1988 and the background level has been decreased by a factor of about three since then.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
There is increasing evidence that Mars may have once been a habitable environment. Gypsum is targeted in the search for Martian biosignatures because it can host extensive cryptoendolithic communities in extreme terrestrial environments and is widespread on Mars. In this study the viability of using different spectroscopy-based techniques to identify the presence of gypsum endolithic communities was investigated by analysing various cryptoendoliths collected from the Lake St. Martin impact crater (LSM), a Mars analogue site found in Manitoba, Canada. Concurrently, the cryptoendolithic microbial community structure present was also analysed to aid in assigning spectroscopic features to microbial community members. Two main morphologies of endolithic communities were collected from gypsum deposits at LSM: true cryptoendolithic communities and annular deposits on partially buried boulders and cobbles <1 cm below the soil surface. Endolithic communities were found to be visibly present only in gypsum with a high degree of translucency and could occur as deep as 3 cm below the exterior surface. The bacterial community was dominated by a phylum (Chloroflexi) that has not been previously observed in gypsum endoliths. The exterior surfaces of gypsum boulders and cobbles are devoid of spectroscopic features attributable to organic molecules and detectable by reflectance, Raman, or ultraviolet-induced fluorescence spectroscopies. However, exposed interior surfaces show unique endolithic signatures detectable by each spectroscopic technique. This indicates that cryptoendolithic communities can be detected via spectroscopy-based techniques, provided they are either partially or fully exposed and enough photon–target interactions occur to enable detection.
The objectives of this article were to determine: 1) students' preferences for college course attributes; and 2) how the amount of course attribute information impacts enrollment. Results indicate students had the highest preferences for face-to-face (F2F) courses offered late morning and early afternoon and two to three days per week. Students selected online over F2F courses depending on course makeup; for example, course topic, online course design technology, and when the F2F version was offered. Additionally, students selected online courses more frequently when additional online course attribute information was available during course selection.