Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel

Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such “blast-plus” concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6–12 months after injury indicated a moderate overall disability in 41/47 (87%) blast-plus TBI subjects and a substantial but smaller number (11/18, 61%, p=0.018) of demographically similar US military controls without TBI evacuated for other medical reasons. Cognitive function assessed with a neuropsychological test battery was not different between blast-plus TBI subjects and controls; performance of both groups was generally in the normal range. No subject was found to have focal neurological deficits. However, 29/47 (57%) of blast-plus subjects with TBI met all criteria for post-traumatic stress disorder (PTSD) versus 5/18 (28%) of controls (p=0.014). PTSD was highly associated with overall disability; 31/34 patients with PTSD versus 19/31 patients who did not meet full PTSD criteria had moderate to severe disability (p=0.0003). Symptoms of depression were also more severe in the TBI group (p=0.05), and highly correlated with PTSD severity (r=0.86, p<0.0001). Thus, in summary, high rates of PTSD and depression but not cognitive impairment or focal neurological deficits were observed 6–12 months after concussive blast-plus-impact complex TBI. Overall disability was substantially greater than typically reported in civilian non-blast concussive (“mild”) patients with TBI, even with polytrauma. The relationship between these clinical outcomes and specific blast-related aspects of brain injuries versus other combat-related factors remains unknown

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

Individually Unique Body Color Patterns in Octopus (Wunderpus photogenicus) Allow for Photoidentification

Studies on the longevity and migration patterns of wild animals rely heavily on the ability to track individual adults. Non-extractive sampling methods are particularly important when monitoring animals that are commercially important to ecotourism, and/or are rare. The use of unique body patterns to recognize and track individual vertebrates is well-established, but not common in ecological studies of invertebrates. Here we provide a method for identifying individual Wunderpus photogenicus using unique body color patterns. This charismatic tropical octopus is commercially important to the underwater photography, dive tourism, and home aquarium trades, but is yet to be monitored in the wild. Among the adults examined closely, the configurations of fixed white markings on the dorsal mantle were found to be unique. In two animals kept in aquaria, these fixed markings were found not to change over time. We believe another individual was photographed twice in the wild, two months apart. When presented with multiple images of W. photogenicus, volunteer observers reliably matched photographs of the same individuals. Given the popularity of W. photogenicus among underwater photographers, and the ease with which volunteers can correctly identify individuals, photo-identification appears to be a practical means to monitor individuals in the wild

Abnormal white matter blood-oxygen-level-dependent signals in chronic mild traumatic brain injury

Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

&lt;p&gt;Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.&lt;/p&gt; &lt;p&gt;Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).&lt;/p&gt; &lt;p&gt;Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.&lt;/p&gt; &lt;p&gt;onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.&lt;/p&gt

How Design Features in Digital Math Games Support Learning and Mathematics Connections

Current research shows that digital games can significantly enhance children’s learning. The purpose of this study was to examine how design features in 12 digital math games influenced children’s learning. The participants in this study were 193 children in Grades 2 through 6 (ages 8-12). During clinical interviews, children in the study completed pre-tests, interacted with digital math games, responded to questions about the digital math games, and completed post-tests. We recorded the interactions using two video perspectives that recorded children’s gameplay and responses to interviewers. We employed mixed methods to analyze the data and identify salient patterns in children’s experiences with the digital math games. The analysis revealed significant gains for 9 of the 12 digital games and most children were aware of the design features in the games. There were eight prominent categories of design features in the video data that supported learning and mathematics connections. Six categories focused on how the design features supported learning in the digital games. These categories included: accuracy feedback, unlimited/multiple attempts, information tutorials and hints, focused constraint, progressive levels, and game efficiency. Two categories were more specific to embodied cognition and action with the mathematics, and focused on how design features promoted mathematics connections. These categories included: linked representations and linked physical actions. The digital games in this study that did not include linked representations and opportunities for linked physical actions as design features did not produce significant gains. These results suggest the key role of mathematics-specific design features in the design of digital math games

Molecular reductions in glucokinase activity increase counter-regulatory responses to hypoglycemia in mice and humans with diabetes.

OBJECTIVE: Appropriate glucose levels are essential for survival; thus, the detection and correction of low blood glucose is of paramount importance. Hypoglycemia prompts an integrated response involving reduction in insulin release and secretion of key counter-regulatory hormones glucagon and epinephrine that together promote endogenous glucose production to restore normoglycemia. However, specifically how this response is orchestrated remains to be fully clarified. The low affinity hexokinase glucokinase is found in glucose-sensing cells involved in glucose homeostasis including pancreatic β-cells and in certain brain areas. Here, we aimed to examine the role of glucokinase in triggering counter-regulatory hormonal responses to hypoglycemia, hypothesizing that reduced glucokinase activity would lead to increased and/or earlier triggering of responses. METHODS: Hyperinsulinemic glucose clamps were performed to examine counter-regulatory responses to controlled hypoglycemic challenges created in humans with monogenic diabetes resulting from heterozygous glucokinase mutations (GCK-MODY). To examine the relative importance of glucokinase in different sensing areas, we then examined responses to clamped hypoglycemia in mice with molecularly defined disruption of whole body and/or brain glucokinase. RESULTS: GCK-MODY patients displayed increased and earlier glucagon responses during hypoglycemia compared with a group of glycemia-matched patients with type 2 diabetes. Consistent with this, glucagon responses to hypoglycemia were also increased in I366F mice with mutated glucokinase and in streptozotocin-treated β-cell ablated diabetic I366F mice. Glucagon responses were normal in conditional brain glucokinase-knockout mice, suggesting that glucagon release during hypoglycemia is controlled by glucokinase-mediated glucose sensing outside the brain but not in β-cells. For epinephrine, we found increased responses in GCK-MODY patients, in β-cell ablated diabetic I366F mice and in conditional (nestin lineage) brain glucokinase-knockout mice, supporting a role for brain glucokinase in triggering epinephrine release. CONCLUSIONS: Our data suggest that glucokinase in brain and other non β-cell peripheral hypoglycemia sensors is important in glucose homeostasis, allowing the body to detect and respond to a falling blood glucose.Yousef Jameel Fund Sir Jukes Thorn Trust Elmore Fund Chang Gung University College of Medicin

MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status

The methylation status of the O6-methylguanine- DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs,