Digital control of the Kuiper Airborne Observatory telescope

The feasibility of using a digital controller to stabilize a telescope mounted in an airplane is investigated. The telescope is a 30 in. infrared telescope mounted aboard a NASA C-141 aircraft known as the Kuiper Airborne Observatory. Current efforts to refurbish the 14-year-old compensation system have led to considering a digital controller. A typical digital controller is modeled and added into the telescope system model. This model is simulated on a computer to generate the Bode plots and time responses which determine system stability and performance parameters. Important aspects of digital control system hardware are discussed. A summary of the findings shows that a digital control system would result in satisfactory telescope performance

Journey to a Heart Safe Community

Riding the Wave of Wellness Conference a UNC-Wilmington from the Building Healthy Academic Communities organizatio

Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males and Females

Background: The adverse childhood experience (ACE) study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age. Methods: 560 (223M/337F) young adults (18–25 years) were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0–4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depressive disorder (MDD) and current symptoms were evaluated by SCID, interview, and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity, or duration of maltreatment across childhood. Results: The most important predictors of lifetime history of MDD were non-verbal emotional abuse in males and peer emotional abuse (EA) in females at 14 years of age, and these were more important predictors across models than number of types of maltreatment (males: t9 = 16.39, p < 10-7; females t9 = 5.78, p < 10-4). Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females. Conclusion: This study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption, and treatment of MDD

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

“Hitting the wall”: Lived experiences of mental health crises

Background : As Norway moves toward the provision of home-based crisis response, knowledge is needed about understandings of mental health crisis and effective ways of addressing crises within the home. Objective : To elicit and learn from service users&#x2019; experiences about the subjective meanings of crisis and what kind of help will be most effective in resolving mental health crises. Theoretical : A phenomenological-hermeneutic cooperative inquiry method was used to elicit and analyse focus group responses from mental health service users who had experienced crises. Results : Findings clustered into three themes: (1) Crisis as multifaceted and varied experiences; (2) losing the skills and structure of everyday life; and (3) complexities involved in family support. Conclusion : Several aspects of crises require an expansion of the biomedical model of acute intervention to include consideration of the personal and familial meaning of the crisis, attention to the home context, and activities of daily living that are disrupted by the crisis, and ways for the person and the family to share in and learn from resolution of the crisis

A possible dose–response association between distance to farmers’ markets and roadside produce stands, frequency of shopping, fruit and vegetable consumption, and body mass index among customers in the Southern United States

Background: The association between farmers’ market characteristics and consumer shopping habits remains unclear. Our objective was to examine associations among distance to farmers’ markets, amenities within farmers’ markets, frequency of farmers’ market shopping, fruit and vegetable consumption, and body mass index (BMI). We hypothesized that the relationship between frequency of farmers’ market shopping and BMI would be mediated by fruit and vegetable consumption. Methods: In 15 farmers’ markets in northeastern North Carolina, July–September 2015, we conducted a crosssectional survey among 263 farmers’ market customers (199 provided complete address data) and conducted farmers’ market audits. To participate, customers had to be over 18 years of age, and English speaking. Dependent variables included farmers’ market shopping frequency, fruit and vegetable consumption, and BMI. Analysis of variance, adjusted multinomial logistic regression, Poisson regression, and linear regression models, adjusted for age, race, sex, and education, were used to examine associations between distance to farmers’ markets, amenities within farmers’ markets, frequency of farmers’ market shopping, fruit and vegetable consumption, and BMI. Results: Those who reported shopping at farmers’ markets a few times per year or less reported consuming 4.4 (standard deviation = 1.7) daily servings of fruits and vegetables, and those who reported shopping 2 or more times per week reported consuming 5.5 (2.2) daily servings. There was no association between farmers’ market amenities, and shopping frequency or fruit and vegetable consumption. Those who shopped 2 or more times per week had a statistically significantly lower BMI than those who shopped less frequently. There was no evidence of mediation of the relationship between frequency of shopping and BMI by fruit and vegetable consumption. Conclusions: More work should be done to understand factors within farmers’ markets that encourage fruit and vegetable purchases.ECU Open Access Publishing Support Fun

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients

A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly

Objective: ATL1103 is a second-generation antisense oligomer targeting the human growth hormone (GH) receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. Design: Twenty-six patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200mg either once or twice weekly for 13 weeks and monitored for a further 8-week washout period. Methods: The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, acid labile subunit (ALS), GH, growth hormone-binding protein (GHBP)), comparison was between baseline and week 14. Safety was assessed by reported adverse events. Results and conclusions: Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups respectively. Compared to baseline, at week 14, twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (P = 0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (P = 0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and remained lower at week 21 than at baseline by a median of 18.7% (P = 0.0005). Compared to baseline, by week 14, IGFBP3 and ALS had declined by a median of 8.9% (P = 0.027) and 16.7% (P = 0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (P = 0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (P = 0.027 and P = 0.005) respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild-to-moderate injection-site reactions. This study provides proof of concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly

The S4–S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating

Human ether-à-go-go-related gene (hERG) K+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel

Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts.

Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans