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The prevalence of Parkinson disease (PD) is growing fast, amplifying the quest for disease-modifying therapies in early disease phases where pathology is still limited. Lifestyle interventions offer a promising avenue for preventing progression from prodromal to manifest PD. We illustrate this primarily for 1 specific lifestyle intervention, namely aerobic exercise because the case for the other main lifestyle factor (dietary interventions) to modify the course of prodromal PD is currently less persuasive. Various observations have hinted at the disease-modifying potential of exercise. First, studies in rodents with experimental parkinsonism showed that exercise elicits adaptive neuroplasticity in basal ganglia circuitries. Second, exercise is associated with a reduced risk of developing PD, suggesting a disease-modifying potential. Third, 2 large trials in persons with manifest PD indicate that exercise can help to stabilize motor parkinsonism, although this could also reflect a symptomatic effect. In addition, exercise seems to be a feasible intervention, given its minimal risk of side effects. Theoretical risks include an increase in fall incidents and cardiovascular complications, but these concerns seem to be acceptably low. Innovative approaches using gamification elements indicate that adequate long-term compliance with regular exercise programs can be achieved, although more work remains necessary to demonstrate enduring adherence for multiple years. Advances in digital technology can be used to deliver the exercise intervention in the participant's own living environment and also to measure the outcomes remotely, which will help to further boost long-term compliance. When delivering exercise to prodromal participants, outcome measures should focus not just on phenoconversion to manifest PD (which may well take many years to occur) but also on measurable intermediate outcomes, such as physical fitness or prodromal nonmotor symptoms. Taken together, there seems to be sufficient evidence to advocate the first judicious attempt of investigating exercise as a disease-modifying treatment in prodromal PD.

The substitution of glutamic acid by valine on the ß-globin chain produces the hemoglobin S variant responsible for sickle cell disease (SCD), a disorder that affects millions of people worldwide and leads to acute and cumulative organ damage. Even though life expectancy has significantly improved where the best medical care is available, there are still few therapeutic options for SCD and those are limited by their availability, cost, and individual toxicities.This review summarizes the clinical data on current treatments for SCD and emerging therapies studied in the acute setting as well as potential disease-modifying agents, with an emphasis on the FDA-approved agents.Hydroxyurea has been a gold standard for two decades, showing benefits in acute complications and overall survival in sickle cell anemia, although data is lacking for certain genotypes such as hemoglobin SC. As progress is made in our understanding of the pathophysiological networks characterizing SCD, numerous pathways appear to be targetable, with L-glutamine, crizanlizumab and voxelotor now approved by the FDA. Pursuing a multi-agent approach could alter the disease course in a more effective fashion and provide an alternative option to curative therapies, but longer clinical studies are needed.

Objective Stereoelectroencephalography (sEEG) is an intracranial encephalography method of expanding use. The need for increased epilepsy surgery access has led to the consideration of sEEG adoption by new or expanding surgical epilepsy programs. Data regarding safety and efficacy are uncommon outside of high‐volume, well‐established centers, which may be less applicable to newer or low‐volume centers. The objective of this study was to add to the sEEG outcomes in the literature from the perspective of a rapidly expanding center. Methods A retrospective chart review of consecutive sEEG cases from January 2016 to December 2019 was performed. Data extraction included demographic data, surgical data, and outcome data, which pertinently examined surgical method, progression to therapeutic procedure, clinically significant adverse events, and Engel outcomes. Results One hundred and fifty‐two sEEG procedures were performed on 131 patients. Procedures averaged 10.5 electrodes for a total of 1603 electrodes. The majority (84%) of patients progressed to a therapeutic procedure. Six clinically significant complications occurred: three retained electrodes, two hemorrhages, and one failure to complete investigation. Only one complication resulted in a permanent deficit. Engel 1 outcome was achieved in 63.3% of patients reaching one‐year follow‐up after a curative procedure. Significance New or expanding epilepsy surgery centers can appropriately consider the use of sEEG. The complication rate is low and the majority of patients progress to therapeutic surgery. Procedural safety, progression to therapeutic intervention, and Engel outcomes are comparable to cohorts from long‐established epilepsy surgery programs.

Contains fulltext : 232804.pdf (Publisher’s version ) (Open Access) BACKGROUND: Interest has risen in identifying individuals at high risk of incident Parkinson's disease (PD) to facilitate inclusion in neuroprotective treatment trials. Current risk estimates of prodromal markers are based on aggregated data of an entire population, but this approach disregards differences in risk estimates by subgroups of a population. In this proof of concept, we determine subgroup-specific risk estimates of olfactory dysfunction for incident PD. METHODS: PubMed, EMBASE and Cochrane were searched for prospective studies investigating the association between olfactory dysfunction and incident PD. Random-effects meta-analysis, subgroup analyses and meta-regression were performed to investigate general and subgroup risk estimates. RESULTS: Individuals with odor identification dysfunction seemed to be at greater risk of incident PD compared to controls without olfactory dysfunction (OR = 4.18; 95%CI [2.47-7.07]). Risk estimates were higher in studies that included higher percentages of women (regression slope β = 0.053 increase in log odds ratio per 1% increase 1%, p = 0.0006), increased with mean study age (β = 0.21 per one year increase; p = 0.005) and in REM-sleep behavior disorder cohorts (β = 1.95; p = 0.03). Furthermore, the association between olfactory dysfunction and incident PD was most distinct in studies with shorter follow-up duration (ß = -0.56; p = 0.0047). CONCLUSION: The presence of olfactory dysfunction conveys a considerably elevated risk of incident PD, likely more in studies with a higher proportion of women, older individuals or short follow-up duration. Individual patient data are warranted to confirm these findings and to yield subgroup-specific risk estimates of other common markers to refine prodromal PD criteria.

Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).

International audience; Recent estimates indicate that ∼70% of the world’s seabird populations have declined since the 1950s due to human activities. However, for almost all bird populations, there is insufficient long-term monitoring to understand baseline (i.e., preindustrial) conditions, which are required to distinguish natural versus anthropogenically driven changes. Here, we address this lack of long-term monitoring data with multiproxy paleolimnological approaches to examine the long-term population dynamics of a major colony of Leach’s Storm-petrel (Hydrobates leucorhous) on Grand Colombier Island in the St. Pierre and Miquelon archipelago—an overseas French territory in the northwest Atlantic Ocean. By reconstructing the last ∼5,800 y of storm-petrel dynamics, we demonstrate that this colony underwent substantial natural fluctuations until the start of the 19th century, when population cycles were disrupted, coinciding with the establishment and expansion of a European settlement. Our paleoenvironmental data, coupled with on-the-ground population surveys, indicate that the current colony is only ∼16% of the potential carrying capacity, reinforcing concerning trends of globally declining seabird populations. As seabirds are sentinel species of marine ecosystem health, such declines provide a call to action for global conservation. In response, we emphasize the need for enlarged protected areas and the rehabilitation of disturbed islands to protect ecologically critical seabird populations. Furthermore, long-term data, such as those provided by paleoecological approaches, are required to better understand shifting baselines in conservation to truly recognize current rates of ecological loss.

Seabird population size is intimately linked to the physical, chemical, and biological processes of the oceans. Yet, the overall effects of long-term changes in ocean dynamics on seabird colonies are difficult to quantify. Here, we used dated lake sediments to reconstruct ~10,000-years of seabird dynamics in the Northwest Atlantic to determine the influences of Holocene-scale climatic oscillations on colony size. On Baccalieu Island (Newfoundland and Labrador, Canada)-where the world's largest colony of Leach's storm-petrel (Hydrobates leucorhous Vieillot 1818) currently breeds-our data track seabird colony growth in response to warming during the Holocene Thermal Maximum (ca. 9000 to 6000 BP). From ca. 5200 BP to the onset of the Little Ice Age (ca. 550 BP), changes in colony size were correlated to variations in the North Atlantic Oscillation (NAO). By contrasting the seabird trends from Baccalieu Island to millennial-scale changes of storm-petrel populations from Grand Colombier Island (an island in the Northwest Atlantic that is subjected a to different ocean climate), we infer that changes in NAO influenced the ocean circulation, which translated into, among many things, changes in pycnocline depth across the Northwest Atlantic basin where the storm-petrels feed. We hypothesize that the depth of the pycnocline is likely a strong bottom-up control on surface-feeding storm-petrels through its influence on prey accessibility. Since the Little Ice Age (LIA), the effects of ocean dynamics on seabird colony size have been altered by anthropogenic impacts. Subsequently, the colony on Baccalieu Island grew at an unprecedented rate to become the world's largest resulting from favorable conditions linked to climate warming, increased vegetation (thereby nesting habitat), and attraction of recruits from other colonies that are now in decline. We show that although ocean dynamics were an important driver of seabird colony dynamics, its recent influence has been modified by human interference.

Accepted manuscript; International audience; Background - Malaria in pregnancy (MiP) contributes significantly to infant mortality rates in sub-Saharan Africa and has consequences on survivors, such as preterm birth and low birth weight. However, its impact on long-term neurocognitive development in children remains unknown. Methods - Our prospective cohort included pregnant women and their live-born singletons from the Malaria in Pregnancy Preventive Alternative Drugs clinical trial. MiP was assessed using microscopy and real-time quantitative polymerase chain reaction (qPCR). Neurocognitive development in children was assessed using the Mullen Scales of Early Learning and the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), at 1 and 6 years of age, respectively. Results - Of 493 pregnant women, 196 (40%) were infected with malaria at least once: 121 (31%) with placental malaria diagnosed by qPCR. Multiple linear regression B-coefficients showed that impaired gross motor scores were associated with MiP at least once (−2.55; confidence interval [95% CI]: −5.15, 0.05), placental malaria by qPCR (−4.95; 95% CI: −7.65, −2.24), and high parasite density at delivery (−1.92; 95% CI: −3.86, 0.02) after adjustment. Malaria and high parasite density at the second antenatal care visit were associated with lower KABC-II Non-Verbal Index scores at 6 years (−2.57 [95% CI: −4.86, −0.28] and −1.91 [−3.51, −0.32]), respectively. Conclusions This prospective cohort study provides evidence that MiP, particularly late term, could have important negative consequences on child development at 1 and 6 years of age. Mechanisms behind this association must be further investigated and diagnostic methods in low-income countries should be strengthened to provide adequate treatment. Clinical Trials Registration NCT00811421.

Background We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. Methods This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. Results Median time on ART was 86.4 months (interquartile range [IQR], 44.8–130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197–484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022–10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028–0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016–0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084–0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198–5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435–7.278], p = 0.005). Conclusion The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

The increasing need for psychiatry services in medically underserved communities has proven to be challenging for health care systems. Caring for this population is complex and can be overwhelming for the inexperienced provider. Proper utilization of psychiatric and mental health nurse practitioners in this setting can expedite meeting the mental health needs of the community. A postgraduate fellowship program that provides supervision and additional training specific to community psychiatry facilitates the transition from novice provider to experienced clinician while aiming to improve retention rates. In this Open Forum, the authors outline the structure of a federally qualified health center's Community Psychiatry Nurse Practitioner Fellowship.

Despite the economic benefits of the oil and gas industry in Northern Alberta, significant concerns exist regarding the impacts of increased oil production on the environment and human health. Several studies have highlighted increases in the concentrations of polycyclic aromatic compounds (PACs) and other hydrocarbons in the atmosphere, water, soil and sediments, plants, wildlife and fish in the Athabasca Oil Sands Region (AOSR) as a result of oil sands industrial activity. Sediment cores can provide information on the temporal trends of contaminants to the environment and provide important baseline information when monitoring data are absent. Here we combined analytical chemistry and a mammalian cell-based bioassay in dated lake sediment cores to assess paleotoxicity in freshwater systems in the AOSR. Sediment intervals were radiometrically dated and subsequently analysed for PACs. PAC extracts from select dated intervals were used in cell-based bioassays to evaluate their endocrine disrupting properties. We demonstrated spatial and temporal variability in the PAC composition of sediment cores around the AOSR with some of the highest concentrations of PACs detected near oil sands industrial activity north of Fort McMurray (AB) in La Saline Natural Area. Recent sediment had positive enrichment factors across most PAC analytes at this site with heavier pyrogenic compounds such as benz(a)anthracene/chrysene and benzofluoranthene/benzopyrene dominating. Our study is the first to link chemical analysis of sediment cores with biological effect assessments of endocrine activity showing feasibility of extending the usefulness of sediment cores in monitoring programs interested in complex mixture assessments. While we observed no spatial or temporal differences in ERα mediated signaling, AhR CALUX results mirrored those of the chemical analysis, demonstrating the utility of coupling biological effects assessments to historical reconstructions of contaminant inputs to the natural environment.

ObjectiveIn this systematic review on drug price comparison studies, we report on recent determinants of drug prices in a national and international context to facilitate regulation of drug prices by purchasers and policymakers worldwide. Determinants of drug prices were divided into non-modifiable and modifiable and were categorised as pertaining to a country’s income level, pharmaceutical market system and its policies and government.Primary outcomeDeterminants of drug prices or price variance.DesignWe systematically searched PubMed, EMBASE, Web of Science and Cochrane Library for peer-reviewed articles published between 2004 and 22 July 2020 that reported an association of the primary outcome with one or more determinants. We performed a best-evidence synthesis of these associations for determinants covered in at least three studies.Results31 publications were included. Only one publication described net drug prices and 30 described retail drug prices. Five modifiable determinants were associated with lower retail prices: generic market portion, discounts, tendering policies, central (governmental) purchasing and pricing regulation schemes. The originators market portion and a system in which mark-ups are common were associated with higher retail prices. Retail prices were highest in the USA, even compared with other high-income countries. A positive association between national income level and drug retail prices could not be established among middle-income and high-income countries. Retail prices were highest in low-income countries when adjusted for purchasing power parity.ConclusionsLiterature on determinants of net drug prices is extremely sparse. Various healthcare system interventions, market-specific and governmental regulations are consistently associated with lower retail prices. Some interventions are easily implementable in developing or middle-income countries, such as tendering, central purchasing and fixed pricing regulation schemes. Net drug price comparison studies are needed to overcome the lack of price transparency and to quantify the effectiveness of policy measures on net drug prices.

Seabirds are thought to provide ecological services such as the movement of nutrients between marine and terrestrial ecosystems, which may be especially critical to productivity and diversity in nutrient-poor environments. Most Arctic ecosystems are unaffected by local human impacts and are naturally nutrient poor and especially sensitive to warming. Here, we assessed the effects of nesting common eider ducks (Somateria mollissima) on soil, vegetation, and pond sediments on island archipelagoes in Hudson Strait between Nunavut and Québec, Canada. Soil, moss, and pond sediments were significantly higher in nitrogen on islands with large numbers of nesting eiders compared to sites with no nesting birds. The highest concentrations of nitrogen in soils and moss occurred at the margins of ponds on eider islands, which correspond to the areas of highest eider use. δ15N and δ34S values in soils, moss, and sediments indicated substantial marine-derived organic matter inputs at the higher nutrient sites. We propose that by foraging on coastal marine benthic invertebrates and returning to islands to nest, eider ducks bio-transport and concentrate marine-derived nutrients to their colony islands, fertilizing Arctic island ecosystems in the process. As common eiders nest on thousands of low to mid-latitude islands throughout the circumpolar Arctic, these nutrient inputs likely dramatically affect biota and ecosystem functioning throughout the tundra biome.

Blood pressure data may vary by measurement technique. We performed a technological assessment of differences in blood pressure measurement between non-invasive blood pressure (NIBP) and invasive arterial blood pressure (ABP) in neurocritically ill patients. After IRB approval, a prospective observational study was performed to study differences in systolic blood pressure (SBP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) values measured by NIBP arm, ABP at level of the phlebostatic axis (ABP heart) and ABP at level of the external auditory meatus (ABP brain) at 30 and 45-degree head of bed elevation (HOB) using repeated measure analysis of covariance and correlation coefficients. Overall, 168 patients were studied with median age of 57 ± 15 years, were mostly female (57%), with body mass index ≤30 (66%). Twenty-three percent (n = 39) had indwelling intracranial pressure monitors, and 19.7% (n = 33) received vasoactive agents. ABP heart overestimated ABP brain for SBP (11.5 ± 2.7 mmHg, p < .001), MAP (mean difference 13.3 ± 0.5 mmHg, p < .001) and CPP (13.4 ± 3.2 mmHg, p < .001). ABP heart overestimated NIBP arm for SBP (8 ± 1.5 mmHg, p < .001), MAP (mean difference 8.6 ± 0.8 mmHg, p < .001), and CPP (mean difference 9.8 ± 3.2 mmHg, p < .001). Regardless of HOB elevation, ABP heart overestimates MAP compared to ABP brain and NIBP arm. Using ABP heart data overestimates CPP and may be responsible for not achieving SBP, MAP or CPP targets aimed at the brain.

Object We review our experience with Parkinson's disease (PD) patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) and then developed noninfectious, non-hemorrhagic, delayed, symptomatic brain edema associated with a DBS lead. Methods All PD patients who underwent STN DBS lead implantation from 2007 to 2015 were included. The same neurosurgeon performed all surgeries, typically in staged fashion, utilizing single pass microelectrode recordings (MER) within a stereotactic frame. A brain CT was obtained in recovery and subsequently if indicated. Results There were 189 patients who underwent 363 STN lead implantations among which 35 (9.6%) represent re-implantations of removed leads in 28 (14.8%) patients. Among the 363 STN leads implanted, there were 12 (3.3%) cases of delayed symptomatic edema associated with a DBS lead involving 10 (5.3%) of the patients studied. Of the 328 leads representing first-time operations, there were 9 (2.1%) cases of delayed symptomatic edema in 7 (3.7%) patients, one of whom (14.3%) presented with seizures. For lead re-implantations, there were 3 (8.6%) cases of the brain edema in 3 (10.7%) patients; all presenting with seizures. For the 35 re-implantations, the trajectory to target was the same or very similar via the same burr hole as prior surgery in 17 (48.6%); 3 (17.6%) of whom developed edema. There was no case of brain edema in the 18 re-operated cases using a different burr opening. Edema patients were treated with a course of anticonvulsant medication and dexamethasone. Lead-associated edema resolved over generally a 4 to 6-week course. Conclusions Noninfectious, non-hemorrhagic, delayed, symptomatic brain edema occurs in approximately 3% of implanted leads and is more common in re-implantations (9%) compared to new implantations (2%). In re-implantations, the edema is more common when the same trajectory is used (18%) compared to a new trajectory (0%). The edema generally occurs 3 to 8 days after implantation, although immediate post-op CT is normal and seizures are a common presenting feature.

This paper aimed to develop a model for understanding the various dimensions of system-based practice (SBP) and determine the extent to which psychiatry residents perform behaviors along these dimensions.Sixty-one supervisors from seven psychiatry programs rated resident performance of SBP behaviors using a 60-item instrument. Multi-dimensional scaling and cluster analysis were conducted to determine how the instrument items related to one another and the larger concept of SBP. Average supervisor ratings between clusters were compared to determine resident performance along the identified SBP dimensions.The data supports a model of SBP defined along two dimensions: (1) from micro (patient) to macro (population-based) interventions and (2) from low to high system complexity. Residents were more likely to perform behaviors at the patient level compared to those at the population-based level.Training in SBP remains predominately focused on the doctor-patient level and not the greater system of health-care delivery.

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396.Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation.This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes.Boston Scientific.

Multidrug-resistant gram-negative (MRGN) bacteria are a serious threat to global health. We used genomics to study MRGN obtained from houseflies in a tertiary Rwandan hospital. Our analysis revealed a high abundance of different MRGN including E. coli pathogenic lineage ST131 suggesting the important role of flies in disseminating highly virulent pathogens in clinical settings and beyond.

Post-operative, non-hemorrhagic, non-infectious symptomatic delayed edema around the DBS lead is an uncommon complication of DBS surgery. We investigated whether this complication impacts clinical outcomes or has long-term sequelae.All Parkinson's disease (PD) patients with subthalamic nucleus (STN) DBS implantation who developed delayed symptomatic lead edema were identified. UPDRS part III motor, Parkinson's Disease Questionnaire (PDQ-39) total and MoCA scores were analyzed to assess motor outcome, quality of life and cognitive status at 1 year.A total of 260 patients underwent 482 STN lead placements. Of these, 16 patients (20 leads, 4.1% of total 482 leads) developed this delayed complication. None of the patients had edema on immediate post-operative scan. Patients presented with varied symptoms including speech difficulty (n = 8), mild confusion (n = 6), headaches (n = 4), gait difficulty (n = 4) and seizures (n = 3). The mean duration for the diagnosis was 5.8 days after lead implantation and the mean duration for which follow-up CT scans reported complete/near complete resolution or improvement of edema was 4.7 weeks (range 2-10 weeks). At 1-year post-DBS, UPDRS motor scores improved significantly (42.5%, p .001); quality of life improved, but the change was not statistically significant (21.3%, p = .197). There was no decline in cognitive function at 1 year (26.6 vs 26.4, p = .567). No long-term complication related to lead edema occurred in these patients.Symptomatic lead edema after DBS surgery is an uncommon complication which typically resolves over time. In our series, there were no long-term sequelae of this complication and clinical outcomes were comparable to that reported in the literature.

This study examined occupational exposures of Ottawa firefighters to combustion by-products and selected metals. We measured exposures to polycyclic aromatic hydrocarbons (PAHs), antimony, cadmium, and lead using (1) personal air samplers worn by firefighters during emergency fire suppression; (2) wipe samples from skin, personal clothing, and personal protective equipment (PPE) collected before and after emergency firefighting (n = 29); and (3) air samples collected in three fire stations vehicle bays, truck cabs, and one administration office. We assessed OFS PPE decontamination procedures using wipe samples collected before and after laundering (n = 12). Air concentrations exceeded occupational exposure limits at two fire events for lead and nine for PAHs. After fire suppression, PAH concentrations were significantly higher on skin and PPE (p

Polyaromatic compounds (PACs) are by-products of combustion and are the major pollutants from the oil and gas industry. However, the mechanism of PACs induced toxicity still remains elusive. The aim of this study was to elucidate the effects of a typical mixture of PACs found in oil sand extract (OSE) on the respiratory, hepatic and nervous systems in humans using in vitro cell culture models followed by non-targeted metabolomics analysis. OSE collected from Alberta, Canada was fractionated into PAC and alkane fractions, and their effects after 24 h exposure on the cell viability measured by MTT assay in three human cell lines (A549, HepG2, and SK-N-SH) were studied. The PAC fractions showed significant dose-dependent cytotoxicity. A549 cells showed the highest sensitivity to OSE extracts, followed by SK-N-SH and HepG2. In contrast, the alkane fractions showed no effects on cell viability. The three human cell lines were further exposed with the PACs at 10% and 20% lethal concentration for 24 h. Metabolomics analysis of the cell extracts indicated that PACs treatments showed different disruptions on possible metabolic pathways on the three cell lines. PACs altered the sex steroid hormone metabolism and regulated the levels of leukotrienes metabolites in all three cell types. The amino acids L-cysteine, L-glutamine, L-tyrosine that are known to cause respiratory effects were significantly up-regulated in A549 cells. The PACs treated HepG2 cells showed down-regulation in metabolites responsible for the inflammatory mediation. Treatment of the differentiated SK-N-SH cells showed up-regulated metabolites involved with butanoate, fatty acid, and pyrimidine metabolism. Leukotriene metabolites were found to be significantly increased in all PACs treated cells. In conclusion, our results showed that PACs in OSE can alter the metabolism of the human lung, liver and neuronal cells and may induce toxicity in multiple target organs.

Hemophilia B is an X linked recessive deficiency of factor IX that presents with a range of clinical severity that co-relates with factor levels. Although guidelines exist to guide perioperative hemostasis in such patients, there is scarce data on elective high-risk neurosurgeries, resulting in a reluctance to offer these patients elective neurosurgeries. These patients thus rarely if ever undergo such procedures. We report a unique case of undiagnosed mild hemophilia B in a gentleman that was found incidentally at age 64 during pre-operative workup. This gentleman had intractable Parkinson's disease for which subthalmic deep brain stimulation was indicated. He was found to have a prolonged APTT on initial lab testing. After subsequent workup, and having excluded the presence of inhibitors, he was diagnosed with Hemophilia B. With the use of Factor IX concentrates (AlphaNine®) and close clinical, laboratory, and radiological monitoring a plan was made for this patient to undergo this procedure. Our patient successfully underwent subthalmic deep brain stimulation with microelectrode recordings and intraoperative test stimulation in a two-step procedure, followed by single channel implantable neurostimulator and extension wire implantations 2 weeks later. The successful peri-operative course of this patient using this novel approach is described, and the need for future data in this regard is emphasized.

Parkinson's disease is a neurodegenerative condition secondary to loss of dopaminergic neurons in the substantia nigra pars compacta. Surgical therapy serves as an adjunct when unwanted medication side effects become apparent or additional therapy is needed. Deep brain stimulation emerged into the forefront in the 1990s. Studies have demonstrated improvement in all of the cardinal parkinsonian signs with stimulation. Frameless and ‘mini-frame’ stereotactic systems, improved MRI for anatomic visualization, and intraoperative MRI-guided placement are a few of the surgical advances in deep brain stimulation. Other advances include rechargeable pulse generators, voltage- or current-based stimulation, and enhanced abilities to ‘steer’ stimulation. Work is ongoing investigating closed-loop ‘smart’ stimulation in which stimulation is predicated on neuronal feedback.

Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD). However, its effect in older patients is not extensively studied, as they are often excluded from DBS surgery due to concerns of complications or reduced benefit. We assessed clinical outcomes after subthalamic nucleus (STN) DBS in older patients (age 75 years) with PD.All PD patients above 75 years who underwent STN-DBS between 1999 and 2015 were included. Unified Parkinson's Disease Rating Scale (UPDRS) scores and Parkinson's Disease Questionnaire (PDQ-39) scores were assessed up to 4 years after surgery. Other measures included were complications/adverse events, levodopa equivalent dose, and cognitive function.A total of 30 patients underwent 52 lead placements. Mean age at surgery was 77.5 years (range 75.0-84.5 years). Post-DBS, motor scores improved by 30.8% after 1-year and 27.3% after a mean of 2.5 years (p .001). All motor sub-scores improved, however axial signs did not change over time. OFF time and dyskinesia duration reduced significantly (p .001), whereas quality of life, activities of daily living and cognitive function did not significantly change. The following adverse events were noted: transient post-operative confusion (36% of patients), gait difficulty (13.3% of patients), hemorrhage (3.8% of leads), personality changes (3.3% of patients), lead revision (1.9% of leads), seizure (1.9% of leads), and infection (1.9% of leads).STN-DBS improves motor outcomes in patients over 75 years of age; however, there was no change in quality of life. Although post-surgical transient confusion was common, there were no serious adverse events and the incidence of other complications was typical for DBS surgery.

Objective Deep brain stimulation (DBS) surgery has proven benefit for several movement disorders and medically-refractory psychiatric conditions and is considered a fairly safe procedure. We sought to determine the national rates, causes, predictors, and outcomes associated with 30-day and 90-day readmission. Patients and Methods The Nationwide Readmissions Database was queried (January-September 2013) using ICD-9-CM codes, identifying patients who underwent DBS for movement disorder (Parkinson’s disease [PD], essential tremor [ET], or dystonia). Variables included categorical age, gender, insurance, comorbidities, type of movement disorder, length of stay (LOS), total costs, and discharge disposition. Results A total of 3392 DBS patients were identified [PD (70.7%), ET (25.6%), dystonia (3.7%)]. The mean age was 64.8 ± 0.4 years old and 37% were female. The rates of unplanned readmissions was 1.9% at 30-days and 4.3% at 90 days. The overall NRD incidence (all patient populations) of 30-day readmission is 11.6%. Readmissions most frequently resulted from surgical complications including hematoma and attention to surgical wounds. Elderly, obese, and those with comorbidities such as history of stroke or CAD are at highest risk. The average LOS, mean total cost, and rate of adverse discharge were worse for 30-day (9 days, $64,520, 71.7%) compared to 90-day readmission (6 days, $52,183, 56.5%). Conclusion All-cause, unplanned readmission for DBS was 1.9% within 30-days and 4.3% within 90-days. Risk factors for readmission in our study, such as advanced age and multiple medical comorbidities, are not unique to DBS. Unplanned readmissions are much rarer following DBS compared to most hospital discharges but can occasionally lead to additional costs and rare complications including hematoma, stroke, and wound infection. DBS should continue to be viewed as a safe and effective treatment modality for a wide range of neurological ailments.

Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators9 discretion. Seizure frequency was determined using daily seizure diaries. Results: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years ( p Conclusion: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.

Occupational exposures to combustion emissions were examined in Ottawa Fire Service (OFS) firefighters. Paired urine and dermal wipe samples (i.e., pre- and post-event) as well as personal air samples and fire event questionnaires were collected from 27 male OFS firefighters. A total of 18 OFS office workers were used as additional controls. Exposures to polycyclic aromatic hydrocarbons (PAHs) and other organic mutagens were assessed by quantification of urinary PAH metabolite levels, levels of PAHs in dermal wipes and personal air samples, and urinary mutagenicity using the Salmonella mutagenicity assay (Ames test). Urinary Clara Cell 16 (CC16) and 15-isoprostane F2t (8-iso-PGF2α) levels were used to assess lung injury and overall oxidative stress, respectively. The results showed significant 2.9- to 5.3-fold increases in average post-event levels of urinary PAH metabolites, depending on the PAH metabolite (p < 0.0001). Average post-event levels of urinary mutagenicity showed a significant, event-related...

Polycyclic aromatic compounds (PAC) are ubiquitous environmental pollutants originating from incomplete combustion processes. While the toxicity of parent PAC such as benzo[a]pyrene (BaP) is well characterized, effects of other alkyl-PAC dibenzothiophene (DBT) and retene (Ret) are not well established. The aim of this study was to examine the underlying relative neurotoxic mechanisms attributed to BaP (parent PAH), DBT and Ret (alkyl-PACs) using human neuroblastoma SK-N-SH cells. The lethal concentrations (LC10 and LC20) were found at approximately 10 µM and 40 µM, respectively after 24-h exposure of SK-N-SH cells. It was hypothesized that PAC trigger reactive oxygen species (ROS) production, leading to activation of apoptotic signaling pathways. Differentiated neuronal cells were treated with three compounds at (0.5-40 µM) for 24 h. There was a significant concentration-dependent increase in levels of ROS, even at sub-lethal levels of 1 µM Ret. The mitochondrial membrane potential (MMP) was significantly decreased. Real-time RT-PCR results showed up-regulation of pro-apoptotic genes and down-regulation of antioxidative genes expression in BaP-, DBT-, and Ret-treated SK-N-SH cells. Cytochrome c protein levels and lipid peroxidation (LPO) were also significantly elevated in a concentration-related manner. Data demonstrated that BaP-, DBT-, or Ret-induced neuronal cell damage involved oxidative stress generation through mitochondria-mediated apoptosis pathway. Alkyl-PAC also exhibited higher potency in ROS induction and reduction of MMP than parent PAC. These findings may be important for environmental risk assessment attributed to exposure to PAC.

Background: Blood lead levels (BLLs) were measured in the adult Inuit population of Nunavut, Northern Canada, during the Inuit Health Survey (IHS) in 2007–2008. Approximately 10% of the adult participants had BLL over the Health Canada's guidance of 100 μg/L. Objectives: 1) To repeat the measurement of BLL among the IHS participants with high BLL and household members including pregnant women and children under 10 years of age; 2) to measure lead (Pb) concentrations in environmental samples to identify potential sources and 3) to explore how Pb from environmental samples contributes to BLL using Pb stable isotopic analyses. Methods: Blood samples were collected from 100 adults and 56 children in 2012. A total of 169 environmental samples (tap water, house dust, paint, country food, soil, and ammunition) were collected from 14 houses from three communities where the IHS participants had the highest BLL. Total Pb concentrations and Pb isotope mass balance were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Results: The geometric mean of BLL was 43.1 μg/L; BLL increased with age and was higher in adults than children (71.1 vs. 17.5 μg/L). Median Pb concentrations in water (1.9 μg/L) and dust (27.1 μg/m2 for wiped dust, 32.6 mg/kg for vacuum dust coarse fraction, and 141.9 mg/kg for vacuum dust fine fraction) were generally higher than in other parts of Canada. Median Pb concentrations of food and soil coarse and fine fractions were low (36.6 μg/kg, 5.4 mg/kg and 11.8 mg/kg respectively); paint chips exceeded the Canadian guidelines in two houses (median: 3.8 mg/kg). Discriminant analyses and isotope ratio analyses showed that ammunition and house dust are major sources of Pb in this study population. Conclusion: Analyses of Pb stable isotopes are useful to identify the routes of exposure to Pb. This approach can contribute to develop targeted public health programmes to prevent Pb exposure. Keywords: Lead, Blood, Environment, Dust, Exposure, Inuit

Human rabies has recently emerged as a significant public health threat in Kinshasa, Democratic Republic of Congo (DRC). However, there is little epidemiological information on human rabies especially in children.We performed at Pediatrics Department of General Reference hospital of Kinshasa between December 2008 and July 2009, a retrospective study to assess the incidence and to describe their clinical aspects and outcome.A total of 21 cases were observed, rather three cases per month. There were 12 boys (57·1%) and 9 girls (42·9%). Biting animal was found to be dog in all cases (100%). The dog was not immunized in all of cases. On admission, all patients (100%) showed furious rabies manifestations. Only two (9·5%) had their wounds treated and received an anti-rabies vaccine (ARV) after the bite incident. Two (9·5%) patients received rabies immunoglobulin (RIG). The case-fatality rate was 100%.The disease emerges as a new major public health problem because of a lack of knowledge regarding rabies risk, the poor management of dog bites. Preventative vaccination for rabies should be recommended in the population of Kinshasa, area at high risk to contract rabies, particularly in children.

The goal of this study was to investigate residency training in the four roles of systems-based practice: patient care advocate, team member, information integrator, and resource manager.The authors surveyed 457 psychiatry residents and fellows across 12 programs from April 2009 to November 2010. Residents were asked to rate the extent in which they were encouraged to perform behaviors consistent with systems-based practice.Approximately 52% residents (n=237) completed the survey. Differences in the average Likert ratings for the four roles were significant [F (3, 4,021)=122.152, p0.001]. Residents were more likely to report routine encouragement to function as a team member (82%, OR=7.2, 95% CI=4.7-11.0), information integrator (77%, OR=5.4, 95% CI=3.6-8.1), or patient care advocate (74%, OR=4.6, 95% CI=3.1-6.8) compared to resource manager (38%).Based upon this study, residency training in resource management is relatively limited compared to other aspects of systems-based practice.

Aims Recent evidence suggests an association between persistent organic pollutants (POPs) and type 2 diabetes. In two First Nations communities where wild food is consumed by a large portion of the population, we compared pollutants in plasma between diabetic and non-diabetic individuals, and investigated the strength of association between pollutants and insulin resistance/secretion in non-diabetic individuals. Methods The study population consisted of 72 participants. Oral Glucose Tolerance Tests were used to assess diabetes status. Plasma was used to determine POP concentrations and mercury concentrations were determined from hair samples. Results Age-adjusted plasma concentrations of some pollutants were significantly higher in diabetic than in non-diabetic individuals. When taking into account age, adiposity levels, and smoking status, POP levels were not associated with insulin resistance nor with insulin secretion in non-diabetic individuals. Conclusions These findings confirm that POP concentrations in plasma may be higher in diabetic than in non-diabetic individuals. No association was however seen between POP concentrations and markers of insulin resistance/secretion in non-diabetic individuals.

In order to improve recruitment into public/community psychiatry fellowships, a survey was administered to understand psychiatry residents' perception of benefits and obstacles to fellowship training. Using standard statistical methods, the responses of those residents who indicated interest in public/community psychiatry training were compared to those who were not. Residents who were interested in public/community psychiatry fellowships were earlier in their training. These same residents gave higher endorsements to items related to quality, location and flexibility of training program, recommendation of colleagues, opportunities for health policy training and networking as compared to residents who were not interested in pursuing a public/community. Those results attained statistical significance while philosophical approaches including emphasis on recovery and tailoring specific training experiences approached significance. Psychiatric residents appear to start residency training with some interest in public/community psychiatry and this interest can be nurtured if public/community psychiatry is emphasized during training.

Soil ingestion rates in the order of 400 mg d − 1 have been proposed and considered plausible for use in human health risk assessments (HHRA) of Aboriginal populations and justified by qualitative assessments of the traditional subsistence activities that could enhance soil ingestion. The purpose of this study was to assess and document the subsistence activities and food consumption practiced by a First Nation Community living in a wilderness community in Canada to allow for a comparison with the previous qualitative assessments of Aboriginal populations and a quantitative mass balance tracer element study of the community conducted concurrently. An ethno-cultural survey was conducted of the Xeni Gwet'in First Nations community living in the Nemiah Valley, approximately 230 km west of Williams Lake, British Columbia. The community diet was observed to consist mainly of fish and big game, and was supplemented by berries and roots. Outdoor cultural gatherings, hunting and food gathering trips and sporting events, with their attendant potential for enhanced soil exposure, were observed to be an important facet of community life. The survey concluded that a significant portion of the Xeni Gwet'in practise a lifestyle similar to the subsistence lifestyles of other indigenous communities, where soil exposure scenarios in the order of hundreds of mg d − 1 have been proposed.

A crisis in the behavioral health care workforce has drawn considerable attention from consumers, families, advocates, clinical professionals, and system administrators at local, state, and federal levels in the past decade. Its effects have been felt in the recruitment, retention, and performance of psychiatrists in the public sector, where a focus on biological aspects of illness and efforts to cut costs have made it difficult for public psychiatrists to engage meaningfully in leadership, consultation, prevention, and psychosocial interventions. An array of training opportunities has recently been created to meet the needs of community psychiatrists at various stages of their careers, from psychiatrists just beginning their careers to those who have been working as medical directors for several years. This article describes the development of these initiatives and their impact on public psychiatry in four key areas--training of experienced psychiatrists, ensuring retention of psychiatrists in community programs, providing fellowship training, and creating professional identity and pride. Although these programs constitute only initial steps, opportunities for psychiatrists to obtain advanced training in community psychiatry are much greater now than they were ten years ago. These initiatives will enhance the professional identity of community psychiatrists and provide a solid foundation for future development of public service psychiatry in the behavioral health workforce.

Post-operative edema around a deep brain stimulation (DBS) lead is a rare presentation. Post-operative edema that is symptomatic, self-limiting and not due to infection, in particular, is rarely reported as a separate entity. We aim to discuss the morphological characteristics of post-operative edema around a DBS lead with an insight into possible etiologies and management. We present eight patients with symptomatic, self-limiting peri-electrode edema post-DBS electrode implantation who presented post-operatively with distinct clinical presentations with imaging that revealed a hypodense area in the white matter surrounding the DBS electrode. Local and systemic tests for infection were negative. The edema resolved over time without surgical intervention. The etiology of the edema remains obscure. The transient nature of the edema and benign course with rapid and full resolution in all our patients cautions against any hasty decision to explant the electrode, in the absence of any obvious signs of infection.

Abnormalities of the portal venous system are a heterogeneous group of conditions that can cause substantial morbidity and mortality and may lead to complications during surgery or percutaneous interventions involving the portal venous system. High-resolution computed tomography, ultrasonography, and magnetic resonance imaging permit a comprehensive, noninvasive evaluation of the portal venous system, enabling the detection of both structural and functional abnormalities. However, an understanding of the embryologic development of the normal portal venous anatomy and anatomic variants is essential to accurately interpret the imaging findings. Knowledge of the characteristic appearances of abnormalities of the portal venous system allows a more confident diagnosis, permitting timely treatment and more informed guidance of surgical procedures and percutaneous interventions, which may lead to an improved outcome.

Now in its 29th year, the Public Psychiatry Fellowship of the New York Psychiatric Institute at Columbia Medical Center selects 10 fellows per year for its 1-year program (1). This award-winning fellowship trains future leaders for the public mental health sector. The curriculum (2) employs a combination of a didactic seminar series, management-problem-focused presentations by guest speakers, field trips, and supervision by fellowship faculty to instill the values and skills required for practice and leadership in the public sector. Fellows utilize the framework of the academic curriculum to carry out a series of presentations throughout the year that allow them to organize, implement and evaluate concepts that they learn during the year. The following account, written from bird's eye view, details one fellow's day at his field placement in a State Hospital outpatient clinic setting, with the aim of illustrating how the concepts taught by the fellowship find application in day to day practice.

First Nations populations in Northwestern Ontario have undergone profound dietary and lifestyle transformations in less than 50 years, which have contributed to the alarming rise in obesity and obesity-related diseases, in particular type 2 diabetes mellitus. Even though the genetic background of First Nations peoples differs from that of the Caucasians, genetics alone cannot explain such a high prevalence in obesity and type 2 diabetes. Modifications in lifestyle and diet are major contributors for the high prevalence of chronic diseases. What remains constant in the literature is the persistent view that locally harvested and prepared foods are of tremendous value to First Nations peoples providing important health and cultural benefits that are increasingly being undermined by western-based food habits. However, the complexities of maintaining a traditional diet require a multifaceted approach, which acknowledges the relationship between benefits, risks and viability that cannot be achieved using purely conventional medical and biological approaches. This brief review explores the biological predispositions and potential environmental factors that contribute to the development of the high incidence of obesity and obesity-related diseases in First Nations communities in Northern Canada. It also highlights some of the complexities of establishing exact physiological causes and providing effective solutions.

The objective of this study was to examine the experience with and safety of brain 1.5 Tesla (T) magnetic resonance imaging (MRI) in deep brain stimulation (DBS) patients. This was a retrospective review of brain MRI scanning performed on DBS patients at the University of Kansas Medical Center between January 1995 and December 2007. A total of 249 DBS patients underwent 445 brain 1.5 T MRI scan sessions encompassing 1,092 individual scans using a transmit-receive head coil, representing the cumulative scanning of 1,649 DBS leads. Patients with complete implanted DBS systems as well as those with externalized leads underwent brain imaging. For the majority of scans, specific absorption rates localized to the head (SAR(H)) were estimated and in all cases SAR(H) were higher than that specified in the present product labeling. There were no clinical or hardware related adverse events secondary to brain MRI scanning. Our data should not be extrapolated to encourage MRI scanning beyond the present labeling. Rather, our data may contribute to further defining safe MRI scanning parameters that might ultimately be adopted in future product labeling as more centers report in detail their experiences.

Quantitative soil ingestion studies employing a mass balance tracer approach have been used to provide a defensible means to estimate soil ingestion for human health risk assessments. Past studies have focused on soil ingestion in populations living in urban/suburban environments. There is a paucity of reliable quantitative soil ingestion data to support human health risk assessments of other lifestyles that may be predisposed to ingesting soil, such as agricultural workers or indigenous populations following traditional lifestyles. The results of a preliminary analysis of sampling and analytical variability that would result from assessing activities typical of populations in rural or wilderness areas and conducted over wide areas show that approximately 225 subject days would be required to detect a difference of 20 mg/d in soil ingestion. Given the typically small populations in these areas, future soil ingestion studies should be focused on specific activities with a high potential for soil ingestion.

Targeting of the subthalamic nucleus (STN) during deep brain stimulation (DBS) surgery using standard atlas coordinates is used in some centers. Such coordinates are accurate for only a subgroup of patients, and subgroup size depends on the extent of inter-individual variation in STN position/size and degree to which atlas represents average anatomical relations. Few studies have addressed this issue.Sixty-two axial T(2)-weighted magnetic resonance (MR) images of the brain (1.5 T) were obtained before STN-DBS in 62 patients (37 males) with Parkinson's disease using a protocol optimized for STN visualization. Image distortion was within sub-millimeter range. Midcommissural point (MCP)-derived coordinates of STN borders, STN center, and other brain landmarks were obtained using stereotactic software. MR-derived measurements were compared to Schaltenbrand and Wahren Atlas.We evaluated 117 best-visualized STNs. STN dimensions and coordinates of its center were highly variable. STN lateral coordinate ranged 8.7 mm-14.5 mm from MCP, A-P coordinate 3.5 mm posterior to 0.5 mm anterior to MCP, and vertical coordinate 1.3 mm-6 mm below MCP. The antero-posterior nucleus dimension varied by 8 mm and lateral-medial dimension by 5.8 mm. Differences between mean values of MR-derived data sets and Atlas values were statistically significant but moderate, excluding AC-PC length, for which the Atlas value was below the 1st percentile of the MR data set. The STN lateral coordinate strongly correlated with the width of the third ventricle (r = 0.73, p0.001).It is now possible to directly evaluate STNs at 1.5 T with minimal image distortion, which reveals variation in STN position and dimensions in the range of nucleus size. This puts under question the rationale of use of standard STN coordinates during DBS surgery.

Objective: Alumni of Columbia University's Public Psychiatry Fellowship were surveyed to assess their use of recovery-oriented practices. Methods: A de novo survey designed specifically for psychiatrists was developed on the basis of prior measures and theories of recovery. A total of 144 graduates completed the survey. Results: Fellowship alumni reported using a variety of practices consistent with a recovery orientation, including asking about patients' social support systems and life goals. To varying degrees, alumni endorsed a belief in the viability of leverage practices. A regression analysis revealed that recovery-oriented practices were associated with awareness of recovery concepts and less authoritarian medication management. Conclusions: Although some recovery-oriented practices were used infrequently (for example, facilitating peer advocacy), a number of important practices were endorsed at relatively high levels. The association of recovery-oriented practices with awareness of recovery concepts suggests that education and advocacy may promote such practices.

The prevailing view is that long-range transport of semivolatile contaminants is primarily conducted by the physical system (e.g., winds, currents), and biological transport is typically ignored. Although this view may be correct in terms of bulk budgets and fluxes, it neglects the potential of animals to focus contaminants into foodwebs due to their behaviors and lifecycles. In particular, gregarious animals that biomagnify and bioaccumulate certain contaminants and then migrate and congregate can become the predominant pathway for contaminants in many circumstances. Fish and birds provide prominent examples for such behavior. This review examines the potential for biovector transport to expose populations to contaminants. In addition, we apply a modeling approach to compare the potential of biovector transport to other physical transport pathways for a hypothetical lake receiving large numbers of fish. We conclude that biovector transport should not be neglected when considering environmental risks of biomagnifying contaminants.