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Abstract To compare awake and asleep deep brain stimulation (DBS) surgery for Essential Tremor (ET), we conducted this retrospective cohort study of patients consecutively operated with DBS targeting the caudal Zona incerta (cZi). 37 underwent surgery awake and 55 asleep. Tremor before surgery and on/off stimulation one year after surgery were evaluated using the Essential Tremor Rating Scale (ETRS). Procedural time, electrode localization, stimulation parameters and adverse events were noted and compared. ETRS scores were similar at baseline between the groups except for contralateral arm tremor, which was slightly worse in the awake group. Total ETRS, contralateral arm tremor and activities of daily living scores showed no significant difference between the groups on-stimulation at one-year follow-up. Compared to the awake group, the asleep group had shorter procedural time and lower stimulation parameters. There were no intracranial haemorrhages nor surgery site-infections. Both groups showed a good improvement of tremor at one-year follow-up. Image-guided DBS surgery targeting the cZi enables safe and efficient asleep surgery for ET.

A common divide-and-conquer approach for Bayesian computation with big data is to partition the data, perform local inference for each piece separately, and combine the results to obtain a global posterior approximation. While being conceptually and computationally appealing, this method involves the problematic need to also split the prior for the local inferences; these weakened priors may not provide enough regularization for each separate computation, thus eliminating one of the key advantages of Bayesian methods. To resolve this dilemma while still retaining the generalizability of the underlying local inference method, we apply the idea of expectation propagation (EP) as a framework for distributed Bayesian inference. The central idea is to iteratively update approximations to the local likelihoods given the state of the other approximations and the prior. The present paper has two roles: we review the steps that are needed to keep EP algorithms numerically stable, and we suggest a general approach, inspired by EP, for approaching data partitioning problems in a way that achieves the computational benefits of parallelism while allowing each local update to make use of relevant information from the other sites. In addition, we demonstrate how the method can be applied in a hierarchical context to make use of partitioning of both data and parameters. The paper describes a general algorithmic framework, rather than a specific algorithm, and presents an example implementation for it.

When the Nebraska Department of Education (NDE) began rethinking Career and Technical Education (CTE) in Nebraska in the early 2000s, it first developed the Nebraska Career Education Model to provide a framework for career awareness and for structuring CTE courses and programs. The model defined six major career fields: agriculture, food, and natural resources; business, marketing, and management; communication and information systems; health sciences; human sciences and education; and skilled and technical sciences. These career fields are further broken down by career clusters, which map out the courses a student needs in order to pursue a career. In a second phase, NDE developed Nebraska Career Connections, a free online career planning and information tool for students and teachers to learn about career fields and pathways. It also links to the Nebraska Department of Labor's workforce trends and information. Adult learners looking for a new career or pursuing postsecondary education also use Career Connections. To implement the Career Education Model, NDE developed a process it called reVISION, in which schools and local communities analyze current career education programs, research school and community needs, and make the adjustments needed to prepare students for postsecondary education and careers. The Nebraska State Board of Education began conversations on Perkins V in spring 2019, anticipating the approval of a state plan in the spring of 2020. NDE and the state board must develop and submit a Perkins V state plan that outlines how the state will comply with the provisions of the federal law, passed in 2018. The state board sees this process as an opportunity and responsibility to build a vision and policy framework around CTE. Although NDE used their regulatory authority in the past to address pieces of the CTE puzzle, now is the time to step back and ensure that the state's policies and regulations build a cohesive system of career education from elementary through high school. A good state plan will point Nebraska toward effective use of regulatory authority that will align policy with practice and fill gaps at the policy and practitioner level. Over the next year, Nebraska will be building on the strong foundation of the reVISION effort to address current gaps in the CTE system. The primary challenge will be linking the Perkins V state plan with work to implement the Every Student Succeeds Act (ESSA), the Individuals with Disabilities Education Act (IDEA), and the Workforce Innovation and Opportunity Act (WIOA).

Essential tremor (ET) is characterized by bilateral upper limb postural and/or kinetic tremor, but also cognitive deficits. Tremor in ET, as well as aspects of cognitive deficits associated with ET, have been suggested to be linked to dysfunction in the cerebello-thalamo-cerebral circuit. In ET patients with disabling and medically intractable motor symptoms, Deep Brain Stimulation (DBS) is effective in reducing tremor. DBS in the caudal Zona incerta (cZi) has been shown to modulate the activity of the sensorimotor cerebello-cerebral circuit during motor tasks. Whether the activity in the cerebello-cerebral circuit is modulated by DBS during tasks involving working memory is unknown. The present study therefore aimed to investigate the possible effects of cZi DBS on working-memory processing in ET patients by means of task-based blood oxygen level-dependent (BOLD) fMRI.Thirteen ET patients completed a working-memory task during DBS OFF and ON conditions. The task involved three conditions: maintenance, manipulation, and control. Behaviorally, there was no significant effect from DBS on accuracy, but a marginally significant Task x DBS interaction was detected for response times (RTs). However, post hoc comparisons for each condition failed to reach statistical significance. FMRI analyses revealed that DBS did not alter BOLD signal in regions of interest (lateral prefrontal cortex, parietal cortex, and the cerebellum), or in a complementary whole-brain analysis.The present study indicates that DBS in the cZi in patients with ET has at most marginal effects on working memory, which is consistent with the results of pre- and post-DBS neuropsychological assessment showing minimal cognitive effects of surgery.

Cyanogenic glucosides are specialized metabolites produced by over 3000 species of higher plants from more than 130 families. The deployment of cyanogenic glucosides is influenced by biotic and abiotic factors in addition to being developmentally regulated, consistent with their roles in plant defense and stress mitigation. Despite their ubiquity, very little is known regarding the molecular mechanisms that regulate their biosynthesis. The biosynthetic pathway of dhurrin, the cyanogenic glucoside found in the important cereal crop sorghum (Sorghum bicolor (L.) Moench), was described over 20 years ago, and yet no direct regulator of the biosynthetic genes has been identified. To isolate regulatory proteins that bind to the promoter region of the key dhurrin biosynthetic gene of sorghum, SbCYP79A1, yeast one-hybrid screens were performed. A bait fragment containing 1204 base pairs of the SbCYP79A1 5′ regulatory region was cloned upstream of a reporter gene and introduced into Saccharomyces cerevisiae. Subsequently, the yeast was transformed with library cDNA representing RNA from two different sorghum developmental stages. From these screens, we identified SbGATA22, an LLM domain B-GATA transcription factor that binds to the putative GATA transcription factor binding motifs in the SbCYP79A1 promoter region. Transient assays in Nicotiana benthamiana show that SbGATA22 localizes to the nucleus. The expression of SbGATA22, in comparison with SbCYP79A1 expression and dhurrin concentration, was analyzed over 14 days of sorghum development and in response to nitrogen application, as these conditions are known to affect dhurrin levels. Collectively, these findings suggest that SbGATA22 may act as a negative regulator of SbCYP79A1 expression and provide a preliminary insight into the molecular regulation of dhurrin biosynthesis in sorghum.

Purpose: Deep brain stimulation (DBS) is often successful in alleviating motor symptoms of essential tremor (ET); however, DBS may also induce adverse speech effects. The caudal zona incerta (cZi) is a promising DBS target for tremor, but less is known about the consequences of cZi DBS for speech. This preliminary study examined how habitual cZi DBS and cZi stimulation at high amplitudes may affect speech function in persons with ET. Method: Fourteen participants with ET were evaluated: off stimulation, on habitual cZi DBS, and with unilateral cZi stimulation at increasing stimulation amplitudes. At each stimulation condition, the participants read three 16-word sentences. Two speech-language pathologists made audio-perceptual consensus ratings of overall speech function, articulation, and voice using a visual sort and rate method. Rated functions when off stimulation, on habitual cZi DBS, and at maximal-amplitude stimulation were compared using Friedman nonparametric tests. For participants with bilateral habitual DBS (n = 5), the effects of bilateral and unilateral stimulation were described in qualitative terms. Results: Habitual cZi DBS had no significant group-level effect on any of the investigated speech parameters. Maximal-amplitude stimulation had a small but significant negative effect on articulation. Participants with reduced articulatory precision (n = 9) had more medially placed electrodes than the nonaffected group (n = 5). Bilateral and unilateral left stimulation had comparable effects on speech. Conclusions: Findings from this preliminary study of cZi DBS indicate that speech is generally not affected by stimulation at habitual levels. High-amplitude cZi stimulation may, however, induce adverse effects, particularly on articulation. Instances of decreased articulatory function were associated with stimulation of more medial electrode contacts, which could suggest cerebello-rubrospinal involvement.

Background: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. Objective: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. Methods: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. Results: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. Conclusion: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Purpose: The aim of this study was to investigate how deep brain stimulation (DBS) of the caudal zona incerta (cZi) affects speech intelligibility in persons with essential tremor. Method: Thirty-five participants were evaluated: off stimulation, on chronic stimulation optimized to alleviate tremor, and during unilateral stimulation at increasing amplitude levels. At each stimulation condition, the participants read 10 unique nonsense sentences from the Swedish Test of Intelligibility. Two listeners, blinded to stimulation condition, transcribed all recorded sentences orthographically in a randomized procedure. A mean speech intelligibility score for each patient and stimulation condition was computed, and comparisons were made between scores off and on stimulation. Results: Chronic cZi-DBS had no significant effect on speech intelligibility, and there was no difference in outcome between bilateral and unilateral treatments. During unilateral stimulation at increasing amplitudes, nine participants demonstrated deteriorating speech intelligibility. These nine participants were on average older and had more superior contacts activated during the evaluation compared with the participants without deterioration. Conclusions: Chronic cZi-DBS, optimized for tremor suppression, does not generally affect speech intelligibility in persons with essential tremor. Furthermore, speech intelligibility may be preserved in many individuals, even when stimulated at high amplitudes. Adverse effects of high-amplitude unilateral stimulation observed in this study were associated with stimulation originating from a more superior location, as well as with the participants' age. These results, highlighting age and stimulation location as contributing to speech intelligibility outcomes, were, however, based on a limited number of individuals experiencing adverse effects with high-amplitude stimulation and should, therefore, be interpreted with caution.

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results.

Abstract Sorghum [Sorghum bicolor (L.) Moench] is an important food crop with a diverse gene pool residing in its wild relatives. A total of 15 sorghum accessions from the unexploited wild gene pool of the Sorghum genus, representing the five subgenera, were sequenced, and the complete chloroplast genomes and 99 common single‐copy concatenated nuclear genes were assembled. Annotation of the chloroplast genomes identified a total of 81 protein‐coding genes, 38 tRNA, and four rRNA genes. The gene content and gene order among the species was identical. A total of 153 nonsynonymous amino acid changes in 40 genes were identified across the species. Phylogenetic analysis of both the whole chloroplast genome and nuclear genes revealed a similar topology with two distinct clades within the genus. The species within the subgenera Eusorghum, Chaetosorghum, and Heterosorghum clustered in one clade, whereas the species within the subgenera Parasorghum and Stiposorghum clustered in a second clade. However, the subgenera Parasorghum and Stiposorghum were not monophyletic, suggesting the need for further research to resolve the relationships within this group. The close relationship between the two monotypic subgenera Chaetosorghum and Heterosorghum suggests that species within these subgenera could be considered as one group. This analysis provides an improved understanding of the genetic relationships within the Sorghum genus and defines diversity in wild sorghum species that may be useful for crop improvement.

BackgroundThe extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI.ObjectiveTo compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline.MethodsStructural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests.ResultsTotal brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group.ConclusionA large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.

Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ​≤ ​0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS ​× ​task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ​≤ ​0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ​≤ ​0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

Abstract An evaluation of Västerbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

Abstract Background The INDEPTH Training & Research Centres of Excellence (INTREC) collaboration developed a training programme to strengthen social determinants of health (SDH) research in low- and middle-income countries (LMICs). It was piloted among health- and demographic researchers from 9 countries in Africa and Asia. The programme followed a blended learning approach and was split into three consecutive teaching blocks over a 12-month period: 1) an online course of 7 video lectures and assignments on the theory of SDH research; 2) a 2-week qualitative and quantitative methods workshop; and 3) a 1-week data analysis workshop. This report aims to summarise the student evaluations of the pilot and to suggest key lessons for future approaches to strengthen SDH research capacity in LMICs. Methods Semi-structured interviews and questionnaires with 24 students from 9 countries in Africa and Asia were used to evaluate each teaching block. Information was collected about the students’ motivation and interest in studying SDH, any challenges they faced during the consecutive teaching blocks, and suggestions they had for future courses on SDH. Results Of the 24 students who began the programme, 13 (54%) completed all training activities. The students recognised the need for such a course and its potential to improve their skills as health researchers. The main challenges with the online course were time management, prior knowledge and skills required to participate in the course, and the need to get feedback from teaching staff throughout the learning process. All students found the face-to-face workshops to be of high quality and value for their work, because they offered an opportunity to clarify SDH concepts taught during the online course and to gain practical research skills. After the final teaching block, students felt they had improved their data analysis skills and were better able to develop research proposals, scientific manuscripts, and policy briefs. Conclusions The INTREC programme has trained a promising cadre of health researchers who live and work in LMICs, which is an essential component of efforts to identify and reduce national and local level health inequities. Time management and technological issues were the greatest challenges, which can inform future attempts to strengthen research capacity on SDH.

Sorghum bicolor (L.) Moench produces the nitrogen-containing natural product dhurrin that provides chemical defense against herbivores and pathogens via the release of toxic hydrogen cyanide gas. Drought can increase dhurrin in shoot tissues to concentrations toxic to livestock. As dhurrin is also a remobilizable store of reduced nitrogen and plays a role in stress mitigation, reductions in dhurrin may come at a cost to plant growth and stress tolerance. Here, we investigated the response to an extended period of water limitation in a unique EMS-mutant adult cyanide deficient class 1 (acdc1) that has a low dhurrin content in the leaves of mature plants. A mutant sibling line was included to assess the impact of unknown background mutations. Plants were grown under three watering regimes using a gravimetric platform, with growth parameters and dhurrin and nitrate concentrations assessed over four successive harvests. Tissue type was an important determinant of dhurrin and nitrate concentrations, with the response to water limitation differing between above and below ground tissues. Water limitation increased dhurrin concentration in the acdc1 shoots to the same extent as in wild-type plants and no growth advantage or disadvantage between the lines was observed. Lower dhurrin concentrations in the acdc1 leaf tissue when fully watered correlated with an increase in nitrate content in the shoot and roots of the mutant. In targeted breeding efforts to down-regulate dhurrin concentration, parallel effects on the level of stored nitrates should be considered in all vegetative tissues of this important forage crop to avoid potential toxic effects.

Earlier research has suggested that approximate Bayesian computation (ABC) makes it possible to fit simulator-based intractable birth–death models to investigate communicable disease outbreak dynamics with accuracy comparable to that of exact Bayesian methods. However, recent findings have indicated that key parameters, such as the reproductive number R, may remain poorly identifiable with these models. Here we show that this identifiability issue can be resolved by taking into account disease-specific characteristics of the transmission process in closer detail. Using tuberculosis (TB) in the San Francisco Bay area as a case study, we consider a model that generates genotype data from a mixture of three stochastic processes, each with its own distinct dynamics and clear epidemiological interpretation. We show that our model allows for accurate posterior inferences about outbreak dynamics from aggregated annual case data with genotype information. As a byproduct of the inference, the model provides an estimate of the infectious population size at the time the data were collected. The acquired estimate is approximately two orders of magnitude smaller than assumed in earlier related studies, and it is much better aligned with epidemiological knowledge about active TB prevalence. Similarly, the reproductive number R related to the primary underlying transmission process is estimated to be nearly three times larger than previous estimates, which has a substantial impact on the interpretation of the fitted outbreak model.

Background: Deep brain stimulation of the motor thalamus or the posterior subthalamic area (PSA) shows promising results for patients with voice tremor, although only for about 50% of patients. There are indications that voice tremor requires more focused stimulation within the target area compared with hand tremor. The objective of the present study was to determine the most efficient location for reducing voice tremor within the PSA. Methods: Thirty-seven patients with essential tremor were evaluated off stimulation and in a set of experimental conditions with unilateral stimulation at increasing amplitude levels. Two listeners performed blinded assessments of voice tremor from recordings of sustained vowel productions. Results: Twenty-five patients (68%) had voice tremor. Unilateral stimulation reduced voice tremor for the majority of patients, and only 6 patients had poor outcomes. Contacts yielding efficient voice tremor reduction were deeper relative to the midcommissural point (MCP) and more posterior relative to the posterior tip of the subthalamic nucleus (pSTN) (zMCP = –3.1, ypSTN = –0.2) compared with poor contacts (zMCP = –0.7, ypSTN = 1.0). High-amplitude stimulation worsened voice tremor for 7 patients and induced voice tremor in 2 patients. Hand tremor improved to a greater extent than voice tremor, and improvements could be seen throughout the target area. Conclusions: Our results indicate that efficient voice tremor reduction can be achieved by stimulating contacts located in the inferior part of the PSA, close or slightly posterior to the pSTN. We observed cases in which voice tremor was induced by high-amplitude stimulation. Key words: Caudal zona incerta, Deep brain stimulation, Electrode location, Essential tremor, Posterior subthalamic area, Voice tremor

In plants, the production of secondary metabolites is considered to be at the expense of primary growth. Sorghum produces a cyanogenic glycoside (dhurrin) that is believed to act as its chemical defence. Studies have shown that acyanogenic plants are smaller in size compared to the wildtype. This study aimed to investigate whether the small plant size is due to delayed germination or due to the lack of dhurrin derived nitrogen. A novel plant system consisting of totally cyanide deficient class 1 (tcd1) and adult cyanide deficient 1 (acdc1) mutant lines was employed. The data for germination, plant height and developmental stage during seedling development and final plant reproductive fitness was recorded. The possible role of phytohormones in recovering the wildtype phenotype, especially in developmentally acyanogenic acdc1 line, was also investigated. The data on plant growth have shown that the lack of dhurrin is disadvantageous to growth, but only at the early developmental stage. The tcd1 plants also took longer to mature probably due to delayed flowering. None of the tested hormones were able to recover the wildtype phenotype. We conclude that the generation of dhurrin is advantageous for plant growth, especially at critical growth stages like germinating seed by providing a ready source of reduced nitrogen.

Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and 12 months after DBS surgery. Nine patients had implantations in the STN, 7 bilaterally and 2 unilaterally (left). Ten had bilateral implantations in the cZi. Postoperative examinations were made off and on stimulation. All patients received simultaneous L-dopa treatment in all conditions. For a series of plosives extracted from a reading passage, absolute and relative measures of duration of frication and amplitude of plosive release were compared between conditions within each treatment group. Results: Relative duration of frication increased in voiceless plosives in the on-stimulation condition in cZi patients. Similar trends were observed across the data set. Duration of prerelease frication and the release peak prominence increased in voiceless plosives on stimulation for both groups. Conclusion: The increased release prominence suggests that patients achieved a stronger closure gesture because of DBS but that the increased energy available resulted in increased frication.

Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight patients were implanted in the STN (ages 51-72 years; M = 63 years). Six received bilateral implantation and 2 unilateral (left) implantation. Eight patients were bilaterally implanted in the cZi (ages 49-71 years; M = 60.8 years). Preoperative assessments were made after a levodopa challenge (approximately 1.5 times the ordinary dose). All postoperative examinations were made off and on stimulation with a clinically optimized dose of levodopa. Measurements of pitch range and variability were obtained from each utterance in a recorded read speech passage. Results: Pitch range and coefficient of variation showed an increase in patients under STN-DBS. Patients under cZi-DBS showed no significant effects of treatment on investigated pitch properties. Conclusion: STN-DBS was shown to increase pitch variation and range. The results provided no evidence of cZi-DBS having a beneficial effect on PD patients' pitch variability.

We investigated time-related patterns in levels of cognitive performance during the period from 1970 to 1993 based on data from Swedish draft boards. The conscripts, including more than a million 18-19-year old men, had taken one of two versions of the Swedish enlistment battery (SEB67; 1970-1979 or SEB80; 1980-1993), each composed of four subtests. The results revealed significant Flynn effects, with estimated gains of 1.2-1.5 IQ-units per decade. The effect seem to hold across ability levels, even though tendencies of more pronounced effects in the lower half of the ability distribution was observed. The largest gains were for visuospatial tests (Paper Form Board and Metal Folding), with little change, even slight losses during the second sub-period, for tests of verbal knowledge (Concept Discrimination and Synonyms) and a mixed pattern for a test of technical comprehension (losses followed by gains). Finally, comparisons of trends in cognitive performance and in standing height show that the gains in cognitive performance over the years from 1980 to 1993 occurred in the absence of overall gains in height, which speaks against nutrition as the cause of the Flynn effects. (Contains 3 tables and 4 figures.)

Background: The Arctic and subarctic area are likely to be highly affected by climate change, with possible impacts on human health due to effects on food security and infectious diseases. Objectives: To investigate the evidence for an association between climatic factors and infectious diseases, and to identify the most climate-sensitive diseases and vulnerable populations in the Arctic and subarctic region. Methods: A systematic review was conducted. A search was made in PubMed, with the last update in May 2013. Inclusion criteria included human cases of infectious disease as outcome, climate or weather factor as exposure, and Arctic or subarctic areas as study origin. Narrative reviews, case reports, and projection studies were excluded. Abstracts and selected full texts were read and evaluated by two independent readers. A data collection sheet and an adjusted version of the SIGN methodology checklist were used to assess the quality grade of each article. Results: In total, 1953 abstracts were initially found, of which finally 29 articles were included. Almost half of the studies were carried out in Canada (n=14), the rest from Sweden (n=6), Finland (n=4), Norway (n=2), Russia (n=2), and Alaska, US (n=1). Articles were analyzed by disease group: food- and waterborne diseases, vector-borne diseases, airborne viral- and airborne bacterial diseases. Strong evidence was found in our review for an association between climatic factors and food- and waterborne diseases. The scientific evidence for a link between climate and specific vector- and rodent-borne diseases was weak due to that only a few diseases being addressed in more than one publication, although several articles were of very high quality. Air temperature and humidity seem to be important climatic factors to investigate further for viral- and bacterial airborne diseases, but from our results no conclusion about a causal relationship could be drawn. Conclusions: More studies of high quality are needed to investigate the adverse health impacts of weather and climatic factors in the Arctic and subarctic region. No studies from Greenland or Iceland were found, and only a few from Siberia and Alaska. Disease and syndromic surveillance should be part of climate change adaptation measures in the Arctic and subarctic regions, with monitoring of extreme weather events known to pose a risk for certain infectious diseases implemented at the community level.

Background: Comparing self-rating health responses across individuals and cultures is misleading due to different reporting behaviors. Anchoring vignettes is a technique that allows identifying and adjusting self-rating responses for reporting heterogeneity (RH). Objective: This article aims to test two crucial assumptions of vignette equivalence (VE) and response consistency (RC) that are required to be met before vignettes can be used to adjust self-rating responses for RH. Design: We used self-ratings, vignettes, and objective measures covering domains of mobility and cognition from the WHO study on global AGEing and adult health, administered to older adults aged 50 years and above from eight low- and middle-income countries in Africa and Asia. For VE, we specified a hierarchical ordered probit (HOPIT) model to test for equality of perceived vignette locations. For RC, we tested for equality of thresholds that are used to rate vignettes with thresholds derived from objective measures and used to rate their own health function. Results: There was evidence of RH in self-rating responses for difficulty in mobility and cognition. Assumptions of VE and RC between countries were violated driven by age, sex, and education. However, within a country context, assumption of VE was met in some countries (mainly in Africa, except Tanzania) and violated in others (mainly in Asia, except India). Conclusion: We conclude that violation of assumptions of RC and VE precluded the use of anchoring vignettes to adjust self-rated responses for RH across countries in Asia and Africa.

Background: The importance of tackling economic, social and health-related inequities is increasingly accepted as a core concern for the post-Millennium Development Goal framework. However, there is a global dearth of high-quality, policy-relevant and actionable data on inequities within populations, which means that development solutions seldom focus on the people who need them most. INTREC (INDEPTH Training and Research Centres of Excellence) was established with this concern in mind. It aims to provide training for researchers from the INDEPTH network on associations between health inequities, the social determinants of health (SDH), and health outcomes, and on presenting their findings in a usable form to policy makers. Objective: As part of a baseline situation analysis for INTREC, this paper assesses the current status of SDH training in three of the African INTREC countries – Ghana, Tanzania, and South Africa – as well as the gaps, barriers, and opportunities for training. Methods: SDH-related courses from the three countries were identified through personal knowledge of the researchers, supplemented by snowballing and online searches. Interviews were also conducted with, among others, academics engaged in SDH and public health training in order to provide context and complementary material. Information regarding access to the Internet, as a possible INTREC teaching medium, was gathered in each country through online searches. Results: SDH-relevant training is available, but 1) the number of places available for students is limited; 2) the training tends to be public-health-oriented rather than inclusive of the broader, multi-sectoral issues associated with SDH; and 3) insufficient funding places limitations on both students and on the training institutions themselves, thereby affecting participation and quality. We also identified rapidly expanding Internet connectivity in all three countries, which opens up opportunities for e-learning on SDH, though the current quality of the Internet services remains mixed. Conclusions: SDH training is currently in short supply, and there is a clear role for INTREC to contribute to the training of a critical mass of African researchers on the topic. This work will be accomplished most effectively by building on pre-existing networks, institutions, and methods.

Background: Selection bias and declining participation rates are of concern in many long-term epidemiological studies. The Västerbotten Intervention Programme (VIP) was launched in 1985 as a response to alarming reports on elevated cardiovascular disease (CVD) mortality in Västerbotten County in Northern Sweden. The VIP invites women and men to a health examination and health counselling during the year of their 40th, 50th, and 60th birthdays. Objective: To evaluate trends in participation rates and determinants of participation in the VIP from 1990 to 2006. Design: Registry data on socio-economic status from Statistics Sweden, and mortality and hospitalisation data from the National Board of Health and Welfare, both covering the whole Swedish population, were linked to the VIP and analysed for participants and non-participants. Results: During 1990–2006, 117,710 individuals were eligible to participate in the VIP, and 40,472 of them were eligible to participate twice. There were 96,560 observations for participants and 61,622 for non-participants. The overall participation rate increased from 56 to 65%. Participants and non-participants had minimal differences in education and age. Initial small differences by sex and degree of urban residence decreased over time. Despite an increasing participation rate in all groups, those with low income or who were single had an approximately 10% lower participation rate than those with high or medium-income or who were married or cohabitating. Conclusion: Sustainability of the VIP is based on organisational integration into primary health care services and targeting of the entire middle-aged population. This enables the programme to meet population expectations of health promotion and to identify high-risk individuals who are then entered into routine preventive health care services. This has the potential to increase participation rates, to minimise social selection bias, and to reinforce other community-based interventions.

INTRODUCTION: injury from motorcycle is a considerable cause of disability and death in the world and especially in low and middle-income countries; it is one of the most serious public health problems. In Cameroon, motorcycle is commonly used for transportation particularly among students. The aim of this paper is to study the risk-factors of the motorcycle-related accidents and injuries among secondary school students in the Tiko municipality, Cameroon. METHODS: a cross sectional study was conducted in January 2012 on 391 students age 16-24 from public and private schools in the Tiko Municipality. Logistic regression was used to estimate the association between risk factors and injuries. A closed-ended and few open-ended questionnaire was used to collect data. RESULTS: the study showed that over 70% of students used motorcycles always or often. Few had undergone any formal training for driving a motorcycle. The vast majority reported not wearing protective gear while driving or riding a motorcycle. Usage of protective gear was particularly low among girls. Over 16% reported using a motorbike always or occasionally under the influence of alcohol or drugs. Over 58% of respondents reported having an accident and over 35% were injured when driving or riding a motorcycle. Those who lived at the Tiko-Douala road have three times higher probability to sustain accidents and injuries than students residing elsewhere (OR 3.19 (1.20-8.46).

Background: National surveys in low-income countries increasingly rely on self-reported measures of health. The ease, speed, and economy of collecting self-reports of health make such collection attractive for rapid appraisals. However, the interpretation of these measures is complicated since different cultures understand and respond to the same question in different ways. Objective: The aim of this pilot study was to develop a culturally sensitive tool to study the self-reported health (SRH) of the local adult population in Burkina Faso. Design: The study was carried out in the 2009 rainy season. The sample included 27 men and 25 women aged 18 or older who live in semi-urban Nouna, Burkina Faso. Three culturally adapted instruments were tested: a SRH question, a wooden visual analogue scale (VAS), and a drawn VAS. Respondents were asked to explain their answers to each instrument. The narratives were analyzed with the content analysis technique, and the prevalence of poor SRH was estimated from the quantitative data by stratification for respondent background variables (sex, age, literacy, education, marital status, ethnicity, chronic diseases). The correlation between the instruments was tested with Spearman's correlation test. Results: The SRH question showed a 38.5% prevalence of poor SRH and 44.2% prevalence with both VAS. The correlation between the VAS was 0.89, whereas the correlation between the VAS and the SRH question was 0.60–0.64. Nevertheless, the question used as the basis of each instrument was culturally sensitive and clear to all respondents. Analysis of the narratives shows that respondents clearly differentiated between the various health statuses. Conclusion: In this pilot, we developed and tested a new version of the SRH question that may be more culturally sensitive than its non-adapted equivalents. Additional insight into this population's understanding and reporting of health was also obtained. A larger sample is needed to further study the validity and reliability of the SRH question and the VAS and understand which instrument is best suited to study SRH in the low-income setting of semi-rural Burkina Faso.

The Västerbotten Intervention Programme (VIP) addresses cardiovascular disease and diabetes in the middle-aged population of Västerbotten County, Sweden. Self-reported health (SRH) is one of the risk factors for both conditions. The aim of this study was to analyse the development patterns of SRH among the VIP participants.Cross-sectional data from 1990 to 2007 were used to analyse the prevalence of poor SRH among 101,396 VIP participants aged 40–60 years. Panel data were used to study the change in SRH among 25,695 persons aged 30–60 years, who participated in the VIP twice within a 10-year interval.Prevalence of poor SRH fluctuated between 1990 and 2007 in Västerbotten County. There was a temporary decline around 2000, with SRH continuously improving thereafter. The majority of panel participants remained in good SRH; over half of those with poor or fair SRH at baseline reported better SRH at follow-up. SRH declined in 19% of the panel participants, mostly among those who had good SRH at the baseline. The decline was common among both women and men, in all educational, age and marital status groups.The SRH improvement among those with poor and fair SRH at baseline suggests that VIP has been successful in addressing its target population. However, the deterioration of SRH among 21% of the individuals with good SRH at baseline is of concern. From a public health perspective, it is important for health interventions to address not only the risk group but also those with a healthy profile to prevent the negative development among the seemingly healthy participants.