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Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention.
Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity.
Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA.
DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.
We survey recent work on approximation algorithms for computing degree-constrained subgraphs in graphs and their applications in combinatorial scientific computing. The problems we consider include maximization versions of cardinality matching, edge-weighted matching, vertex-weighted matching and edge-weighted
-matching, and minimization versions of weighted edge cover and
-edge cover. Exact algorithms for these problems are impractical for massive graphs with several millions of edges. For each problem we discuss theoretical foundations, the design of several linear or near-linear time approximation algorithms, their implementations on serial and parallel computers, and applications. Our focus is on practical algorithms that yield good performance on modern computer architectures with multiple threads and interconnected processors. We also include information about the software available for these problems.
Three new tephras have been identified in Southeast Alaska. An 8-cm-thick black basaltic tephra with nine discrete normally graded beds is present in cores from a lake on Baker Island. The estimated age of the tephra is 13,492 ± 237 cal yr BP. Although similar in age to the MEd tephra from the adjacent Mt. Edgecumbe volcanic field, this tephra is geochemically distinct. Black basaltic tephras recovered from two additional sites in Southeast Alaska, Heceta Island and the Gulf of Esquibel, are also geochemically distinct from the MEd tephra. The age of the tephra from Heceta Island is 14,609 ± 343 cal yr BP. Whereas the tephras recovered from Baker Island/Heceta Island/Gulf of Esquibel are geochemically distinct from each other, similarities in the ages of these tephras and the MEd tephra suggest a shared eruptive trigger, possibly crustal unloading caused by retreat of the Cordilleran Ice Sheet. The submerged Addington volcanic field on the continental shelf, which may have been subaerially exposed during the late Pleistocene, is a possible source for the Southeast Alaska tephras.
Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.
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.
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.
The proximity of minerals found in human hard tissues may influence cell phenotype. Since cells respond to a range of environmental cues, this study sought to identify the influence of two apatite-based microparticles, hydroxyapatite (HA) and fluoroapatite (FA), upon dental and bone cells. After bone marrow stromal cells (BMSCs), 7F2 osteoblasts and dental pulp stem cells (DPSCs) were plated into media with or without HA or FA particles, the cells were analyzed for alkaline phosphatase (ALP) production, collagen I production, osteocalcin production, and mineralization for two weeks. The BMSCs and DPSCs in media without any microparticles produced more ALP compared to those with microparticles from Day 5 forward. In addition, the collagen I and osteocalcin production in cultures without microparticles was higher than in cultures containing either HA or FA particles. While some studies have shown increased osteogeonic differentiation in the presence of mineral particles, those studies used nanoparticles that were able to be internalized by the cells and were smaller than the microparticles used in this study.
Observational evidence suggests that increased whole grain (WG) intake reduces the risks of many non-communicable diseases, such as CVD, type 2 diabetes, obesity and certain cancers. More recently, studies have shown that WG intake lowers all-cause and cause-specific mortality. Much of the reported evidence on risk reduction is from US and Scandinavian populations, where there are tangible WG dietary recommendations. At present there is no quantity-specific WG dietary recommendation in the UK, instead we are advised to choose WG or higher fibre versions. Despite recognition of WG as an important component of a healthy diet, monitoring of WG intake in the UK has been poor, with the latest intake assessment from data collected in 2000–2001 for adults and in 1997 for children. To update this information we examined WG intake in the National Diet and Nutrition Survey rolling programme 2008–2011 after developing our database of WG food composition, a key resource in determining WG intake accurately. The results showed median WG intakes remain low in both adults and children and below that of countries with quantity-specific guidance. We also found a reduction in C-reactive protein concentrations and leucocyte counts with increased WG intake, although no association with other markers of cardio-metabolic health. The recent recommendations by the UK Scientific Advisory Committee on Nutrition to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of public health policy to promote consumption of these important foods.
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 remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.
We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.
Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.
During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.
To develop an automated method for ventilator-associated condition (VAC) surveillance and to compare its accuracy and efficiency with manual VAC surveillance
The intensive care units (ICUs) of 4 hospitals
This study was conducted at Detroit Medical Center, a tertiary care center in metropolitan Detroit. A total of 128 ICU beds in 4 acute care hospitals were included during the study period from August to October 2013. The automated VAC algorithm was implemented and utilized for 1 month by all study hospitals. Simultaneous manual VAC surveillance was conducted by 2 infection preventionists and 1 infection control fellow who were blinded to each another’s findings and to the automated VAC algorithm results. The VACs identified by the 2 surveillance processes were compared.
During the study period, 110 patients from all the included hospitals were mechanically ventilated and were evaluated for VAC for a total of 992 mechanical ventilation days. The automated VAC algorithm identified 39 VACs with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%. In comparison, the combined efforts of the IPs and the infection control fellow detected 58.9% of VACs, with 59% sensitivity, 99% specificity, 91% PPV, and 92% NPV. Moreover, the automated VAC algorithm was extremely efficient, requiring only 1 minute to detect VACs over a 1-month period, compared to 60.7 minutes using manual surveillance.
The automated VAC algorithm is efficient and accurate and is ready to be used routinely for VAC surveillance. Furthermore, its implementation can optimize the sensitivity and specificity of VAC identification.
Infect. Control Hosp. Epidemiol. 2015;36(9):999–1003
Background: Ischemic stroke secondary to NBTE is a rare complication of systemic malignancies. Although previously reported in gynecological cancers, this occurrence is infrequent. Furthermore, stroke pre-dating the gynecological malignancy diagnosis has rarely been reported. Methods: Case presentations and literature review. Results: Case1: A 48-year-old woman presented with acute dysarthria and left facial weakness caused by a right middle cerebral artery (MCA) infarct. Mitral valve vegetations were found on a transthoracic echocardiogram (TTE). A malignancy screen uncovered a pelvic endometrial adenocarcinoma. Case 2: A 49-year-old woman developed acute right hand weakness. A CT head scan showed a left pre-central gyrus infarct. Her TEE revealed aortic valve vegetations. An ovarian neoplasm was then discovered. Case 3: A 36-year-old woman with a known diagnosis of cervical squamous cell carcinoma developed acute left-sided weakness secondary to a right MCA stroke. Aortic valve vegetations were seen on TTE. Conclusions: We have reported three cases of NBTE where the underlying malignancy was gynecological. In the first two cases, the malignancy was discovered while investigating for the stroke mechanism, while the third had a known underlying malignancy. This series highlights the need to consider gynecological malignancies as an underlying cause of stroke in young women; and that the ischemic event can occur prior to the malignancy diagnosis.
Increased whole grain intake has been shown to reduce the risk of many non-communicable diseases. Countries including the USA, Canada, Denmark and Australia have specific dietary guidelines on whole grain intake but others, including the UK, do not. Data from 1986/87 and 2000/01 have shown that whole grain intake is low and declining in British adults. The aim of the present study was to describe whole grain intakes in the most current dietary assessment of UK households using data from the National Diet and Nutrition Survey rolling programme 2008–11. In the present study, 4 d diet diaries were completed by 3073 individuals between 2008 and 2011, along with details of socio-economic status (SES). The median daily whole grain intake, calculated for each individual on a dry weight basis, was 20 g/d for adults and 13 g/d for children/teenagers. The corresponding energy-adjusted whole grain intake was 27 g/10 MJ per d for adults and 20 g/10 MJ per d for children/teenagers. Whole grain intake (absolute and energy-adjusted) increased with age, but was lowest in teenagers (13–17 years) and younger adults up to the age of 34 years. Of the total study population, 18 % of adults and 15 % of children/teenagers did not consume any whole-grain foods. Individuals from lower SES groups had a significantly lower whole grain intake than those from more advantaged classifications. The whole grain intake in the UK, although higher than in 2000/01, remains low and below that in the US and Danish recommendations in all age classes. Favourable pricing with increased availability of whole-grain foods and education may help to increase whole grain intake in countries without whole-grain recommendations. Teenagers and younger adults may need targeting to help increase whole grain consumption.
Epidemiological evidence suggests an inverse association between whole grain consumption and the risk of non-communicable diseases, such as CVD, type 2 diabetes, obesity and some cancers. A recent analysis of the National Diet and Nutrition Survey rolling programme (NDNS-RP) has shown lower intake of whole grain in the UK. It is important to understand whether the health benefits associated with whole grain intake are present at low levels of consumption. The present study aimed to investigate the association of whole grain intake with intakes of other foods, nutrients and markers of health (anthropometric and blood measures) in the NDNS-RP 2008–11, a representative dietary survey of UK households. A 4-d diet diary was completed by 3073 individuals. Anthropometric measures, blood pressure levels, and blood and urine samples were collected after diary completion. Individual whole grain intake was calculated with consumers categorised into tertiles of intake. Higher intake of whole grain was associated with significantly decreased leucocyte counts. Significantly higher concentrations of C-reactive protein were seen in adults in the lowest tertile of whole grain intake. No associations with the remaining health markers were seen, after adjustments for sex and age. Over 70 % of this population did not consume the minimum recommend intake associated with disease risk reduction, which may explain small variation across health markers. Nutrient intakes in consumers compared with non-consumers were closer to dietary reference values, such as higher intakes of fibre, Mg and Fe, and lower intakes of Na, suggesting that higher intake of whole grain is associated with improved diet quality.
The impact of the 2013 NHSN CAUTI definition on CAUTI rates was analyzed. A total of 107 CAUTI episodes were identified; 60 according to NHSN 2013 definitions only and 47 according to the 2012 and 2013 definitions. Physician-diagnosed “other infections” were more common among patients who had CAUTI only according to NHSN 2013 definitions (P<.001).