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This research relates to the design, modelling and fabrication of 3D metal printed heat sinks. The heat sinks presented in the research are the commonly used longitudinal fin solid heat sink (LFSHS) and three LFSHS lattice structure designs, differing only in their lattice sizes, fabricated using the Direct Metal Laser Sintering (DMLS) technique in Maraging Steel (MS1), on an EOSINT M280 system. In order to increase the heat sink surface area, the heat sinks are manufactured with mesh lattices along the length of the fins, while keeping the overall heat sink volume constant. The research is focused on pushing the limitations of the DMLS technique for the development of repeating unit, lattice structures heat sinks, and to examine the effect of incrementally varying the lattice sizes with regards to the resultant surface area of the heat sink and the thermal performance of the system. The results obtained under natural convection show that the thermal performance of the LFSHS outperformed all lattice structure heat sinks. This is due to the fact that, the pressure drop across the lattice heat sinks were so high, due to lattice meshes that it negated the positive effect of the greater surface area. [ABSTRACT FROM AUTHOR]

Abstract: Brain-derived neurotrophic factor (BDNF) was the first purified molecule identified to directly support the development of mesencephalic dopamine neurons. However, its physiologic role has remained unknown. Based on patterns of expression, it is unlikely to serve as a target-derived neurotrophic factor, but it may instead act locally in the mesencephalon, either released by afferent projections, or in autocrine fashion. To assess a possible local role, we blocked BDNF signaling in the substantia nigra (SN) of postnatal rats by injection of either neutralizing antibodies or a peptide antagonist. These treatments increased the magnitude of developmental cell death in the SN, indicating that endogenous local BDNF does play a regulatory role. However, we also find that elimination of BDNF in brain throughout postnatal development in BDNFfl/fl:Nestin-Cre mice has no effect on the adult number of SN dopamine neurons. We postulate that other forms of trophic support may compensate for the elimination of BDNF during early development. Although the number of SN dopamine neurons is unchanged, their organization is disrupted. We conclude that BDNF plays a physiologic role in the postnatal development of SN dopamine neurons. [Copyright &y& Elsevier]

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of neurotrophic factors. BDNF has long been recognized to have potential for the treatment of a variety of human neurodegenerative diseases. However, clinical trials with recombinant BDNF have yet to yield success, leading to the suggestion that alternative means of harnessing BDNF actions for therapeutic use may be required. Here we describe an approach to create low molecular weight peptides that, like BDNF, promote neuronal survival. The peptides were designed to mimic a cationic tripeptide sequence in loop 4 of BDNF shown in previous studies to contribute to the binding of BDNF to the common neurotrophin receptor p75NTR. The best of these peptides, the cyclic pentapeptide 2 (cyclo(-D-Pro-Ala-Lys-Arg-)), despite being of low molecular weight (Mr 580), was found to be an effective promoter of the survival of embryonic chick dorsal root ganglion sensory neurons in vitro (maximal survival, 68 ± 3% of neurons supported by BDNF). Pentapeptide 2 did not affect the phosphorylation of either TrkB (the receptor tyrosine kinase for BDNF) or the downstream signaling molecule MAPK, indicating that its mechanism of neuronal survival action is independent of TrkB. NMR studies reveal that pentapeptide 2 adopts a well defined backbone conformation in solution. Furthermore, pentapeptide 2 was found to be effectively resistant to proteolysis when incubated in a solution of rat plasma in vitro. These properties of pentapeptide 2 (low molecular weight, appropriate pharmacological actions, a well defined solution conformation, and proteolytic stability) render it worthy of further investigation, either as a template for the further design of neuronal survival promoting agents or as a lead compound with therapeutic potential in its own right. [ABSTRACT FROM AUTHOR]

Focuses on the eligibility for Supplemental Security Income (SSI) among the elderly in the U.S. Factors which affect participation; Potential effects of various options to modify financial eligibility standards for the federal SSI program; Descriptive data on eligibility and participation.

Objectives: To estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use., Methods: We employed a retrospective cohort study design using Washington State workers' compensation data for 1994-2000 injuries linked to US Social Security Administration earnings and mortality data and National Death Index (NDI) cause of death data from 1994 to 2018. We categorised injuries as lost-time versus medical-only, where the former involved more than 3 days off work or permanent disability. We determined death status and cause of death from NDI records. We modelled separate Fine and Gray subdistribution hazard ratios (sHRs) and 95% CIs for injured men and women for opioid-related and all drug-related mortality through 2018. We used quantitative bias analysis to account for unmeasured confounding by preinjury opioid use., Results: The hazard of opioid-related mortality was elevated for workers with lost-time relative to medical-only injuries: sHR for men: 1.53, 95% CI 1.41 to 1.66; for women: 1.31, 95% CI 1.16 to 1.48. Accounting for preinjury opioid use, effect sizes were reduced but remained elevated: sHR for men was 1.43, 95% simulation interval (SI) 1.20 to 1.69; for women: 1.27, 95% SI 1.10 to 1.45., Conclusions: Occupational injuries and illnesses severe enough to require more than 3 days off work are associated with an increase in the hazard of opioid-related mortality. The estimated increase is reduced when we account for preinjury opioid use, but it remains substantial. Reducing work-related injuries and postinjury opioid prescribing and improving employment and income security may decrease opioid-related mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: An intensive lifestyle intervention (ILI) has been shown to improve diabetes management and physical function. These benefits could lead to better labor market outcomes, but this has not been previously studied., Objective: To estimate the association of an ILI for weight loss in type 2 diabetes with employment, earnings, and disability benefit receipt during and after the intervention., Design, Setting, and Participants: This cohort study included participants with type 2 diabetes and overweight or obesity and compared an ILI with a control condition of diabetes support and education. Data for the original trial were accrued from August 22, 2001, to September 14, 2012. Trial data were linked with Social Security Administration records to investigate whether, relative to the control group, the ILI was associated with improvements in labor market outcomes during and after the intervention period. Difference-in-differences models estimating relative changes in employment, earnings, and disability benefit receipt between the ILI and control groups were used, accounting for prerandomization differences in outcomes for linked participants. Outcome data were analyzed from July 13, 2020, to May 17, 2023., Exposure: The ILI consisted of sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists on a weekly basis in the first 6 months, decreasing to a monthly basis by the fourth year, designed to achieve and maintain at least 7% weight loss. The control group received group-based diabetes education sessions 3 times annually during the first 4 years, with 1 annual session thereafter., Main Outcomes and Measures: Employment and receipt of federal disability benefits (Supplemental Security Income and Social Security Disability Insurance), earnings, and disability benefit payments from 1994 through 2018., Results: A total of 3091 trial participants were linked with Social Security Administration data (60.1% of 5145 participants initially randomized and 97.0% of 3188 of participants consenting to linkage). Among the 3091 with fully linked data, 1836 (59.4%) were women, and mean (SD) age was 58.4 (6.5) years. Baseline clinical and demographic characteristics were similar between linked participants in the ILI and control groups. Employment increased by 2.9 (95% CI, 0.3-5.5) percentage points for the ILI group relative to controls (P = .03) with no significant relative change in disability benefit receipt (-0.9 [95% CI, -2.1 to 0.3] percentage points; P = .13)., Conclusions and Relevance: The findings of this cohort study suggest that an ILI to prevent the progression and complications of type 2 diabetes was associated with higher levels of employment. Labor market productivity should be considered when evaluating interventions to manage chronic diseases.

Objectives: To measure the impact of lost-time occupational injuries on all-cause mortality in Washington State and, using the same data elements and study design, to determine whether the estimated impact was similar to previous estimates for New Mexico., Methods: We linked injuries in the Washington workers' compensation system with Social Security Administration data on earnings and mortality. We estimated Cox survival models of mortality for women and men with lost-time compared with medical-only injuries, adjusting for age, pre-injury earnings and industry. We used quantitative bias analysis to account for confounding by pre-injury smoking and obesity., Results: The estimated mortality HR was 1.24 for women (95% CI 1.21 to 1.28) and 1.22 for men (95% CI 1.20 to 1.24). After adjusting for unmeasured pre-injury smoking and obesity, the estimated HR for women was 1.10, 95% simulation interval (SI) 1.00 to 1.21; for men, it was 1.15, 95% SI 1.04 to 1.27., Conclusions: All-cause mortality for Washington workers with lost-time injuries was higher than for those with medical-only injuries. Estimated HRs for Washington were consistent with those previously estimated for New Mexico, a less populous state with lower median wages and a different workers' compensation insurance mechanism. This suggests that the relationship between workplace injury and long-term mortality may be generalisable to other US states. These findings support greater efforts to enhance safety and to investigate factors that improve postinjury employment opportunities and long-term health. This association should be examined in additional locations, with different study conditions, or using additional data on pre-injury risk factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Antimicrobial peptides are an ancient and innate system of host defence against a wide range of microbial assailants. Mechanistically, unstructured peptides undergo a secondary structure transition into amphipathic α-helices, upon contact with membrane surfaces. This leads to peptide binding and removal of the membrane components in a detergent-like manner or via self-organisation into trans-membrane pores (either barrel-stave or toroidal pore) thereby destroying the microbe. Self-assembly of antimicrobial peptides into oligomers and ultimately amyloid has been mostly examined in parallel, however recent findings link diseases, such as Alzheimer's disease as an aberrant activity of a protective neuropeptide with antimicrobial activity. These self-assembled oligomers can also interact with membranes. Here, we review those antimicrobial peptides reported to self-assemble into amyloid, where supported by structural evidence. We consider their membrane activities as antimicrobial peptides and present evidence of consistent self-assembly patterns across major evolutionary groups. Trends are apparent across these groups, supporting the mounting data that self-assembly of antimicrobial peptides into amyloid should be considered as synergistic to the antimicrobial peptide response., (© 2022 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Cobalt-mediated radical polymerizations (CMRPs) have been initiated by the radical decarboxylation of tetrachlorophthalimide activated esters. This allows for the controlled radical polymerization of activated monomers across a broad temperature range with a single cobalt species, with the incorporation of polymer end groups derived from simple carboxylic acid derivatives and termination with an organozinc reagent. This method has been applied to the synthesis of a polymer/graphene conjugate and a water-soluble protein/polymer conjugate, demonstrating the first examples of CMRP in graphene and protein conjugation., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Drug overdoses and suicides have been rising since 2000 and are major contributors to a 3-year decline in US life expectancy. Studies suggest that injured workers have elevated rates of depression and opioid use, but no studies have measured excess mortality related to these risks., Materials and Methods: We linked New Mexico workers' compensation data for 100 806 workers injured in 1994 through 2000 with Social Security Administration earnings and mortality data through 2013 and National Death Index cause of death data. We then estimated the association between receiving lost-time workers' compensation benefits and mortality hazard ratios (HRs) and 95% confidence intervals (CIs) based on Fine and Gray cause-specific subdistribution hazards for common causes of death and for drug-related, suicide, and alcohol-related mortality., Results: There was almost a 3-fold increase in combined drug-related and suicide mortality hazard among women (HR = 2.63, 95% CI = 1.91-3.64) and a substantial increase among men (HR = 1.42, 95% CI = 1.13-1.79). Circulatory disease mortality hazard was elevated for men (HR = 1.25, 95% CI = 1.05-1.50)., Conclusion: Workplace injuries severe enough to require more than a week off work may impair workers' long-term health and well-being. Drug-related deaths and suicides may be important contributors to the long-term excess mortality of injured workers. Improved workplace conditions, improved pain treatment, better treatment of substance use disorders, and treatment of postinjury depression may substantially reduce mortality consequent to workplace injuries., (© 2019 Wiley Periodicals, Inc.)

In this paper, we estimate the impact of Medicaid expansions via the Patient Protection and Affordable Care Act (ACA) on applications to federal disability programs in 14 states that expanded Medicaid in January 2014. We use a difference-in-differences regression model to compare disability application rates in geographic areas within states that expanded Medicaid to rates in areas of non-expansion states that were carefully selected using a matching approach that accounts for state Medicaid policies pre-ACA as well as demographic and socioeconomic characteristics that might influence disability application rates. We find a slower decrease in Supplemental Security Income (SSI) application rates after Medicaid expansions in expansion states relative to non-expansion states, with application rates declining in both state groups from 2014 through 2016. Our analysis of the impact of the Medicaid expansions on Social Security Disability Insurance (SSDI) application rates was inconclusive for reasons we discuss in the paper.

Background: Little research has examined the relationship between non-fatal workplace injuries and illnesses, and long-term mortality., Methods: We linked non-fatal injury cases reported to the New Mexico workers' compensation system for 1994-2000 with Social Security Administration data on individual earnings and mortality through 2014. We then derived sex-specific Kaplan-Meier curves to show time to death for workers with lost-time injuries (n = 36,377) and comparison workers (n = 70,951). We fit multivariable Cox survival models to estimate the hazard ratio separately for male and female workers with lost-time injuries., Results: The estimated hazard ratio for lost-time injuries is 1.24 for women and 1.21 for men. Ninety-five percent confidence intervals were 1.15, 1.35 and 1.15, 1.27, respectively., Conclusion: Lost-time occupational injuries are associated with a substantially elevated mortality hazard. This implies an important formerly unmeasured cost of these injuries and a further reason to focus on preventing them. Am. J. Ind. Med. 59:1061-1069, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: We combined federal and state administrative data to study the long-term earnings losses associated with occupational injuries and assess the adequacy of workers' compensation benefits., Methods: We linked state data on workers' compensation claims from New Mexico for claimants injured from 1994 to 2000 to federal earnings records from 1987 to 2007. We estimated earnings losses up to 10 years after injury and computed the fraction of losses replaced by benefits., Results: Workers with lost-time injuries lost an average of 15% of their earnings over the 10 years after injury. On average, workers' compensation income benefits replaced 16% of these losses. Men and women had similar losses and replacement rates. Workers with minor injuries had lower losses but also had lower replacement rates., Conclusion: Earnings losses after an injury are highly persistent, even for comparatively minor injuries. Income benefits replace a smaller fraction of those losses than previously believed., (© 2014 Wiley Periodicals, Inc.)

Workplace injuries and illnesses are an important cause of disability. State workers' compensation programs provide almost $60 billion per year in cash and medical-care benefits for those injuries and illnesses. Social Security Disability Insurance (DI) is the largest disability insurance program in the United States, with annual cash payments to disabled workers of $95 billion in 2008. Because injured workers may also receive DI benefits, it is important to understand how those two systems interact to provide benefits. This article uses matched state workers' compensation and Social Security data to study the relationship between workplace injuries and illnesses and DI benefit receipt. We find that having a lost-time injury substantially increases the probability of DI receipt, and, for people who become DI beneficiaries, those with injuries receive DI benefits at younger ages. This relationship remains robust even after we account for important personal and work characteristics.

The articles in this special issue present findings from research on the employment and work-related activities of individuals receiving benefits through the Social Security Disability Insurance and Supplemental Security Income programs, and on the factors that hinder their efforts to work at levels that lead to exiting the disability rolls. This article introduces the other articles, highlights their important findings, and discusses the implications for ongoing efforts to increase the earnings and self-sufficiency of these beneficiaries, such as the Ticket to Work program and the Benefit Offset National Demonstration.

We use linked administrative data from program and earnings records to summarize the 2007 employment rates of Social Security disability program beneficiaries at the national and state levels, as well as changes in employment since 1996. The findings provide new information on the employment activities of beneficiaries that should be useful in assessing current agency policies and providing benchmarks for ongoing demonstration projects and future return-to-work initiatives. The overall employment rate--which we define as annual earnings over $1,000--was 12 percent in 2007. Substantial variation exists within the population. Disability Insurance beneficiaries and those younger than age 40 were much more likely to work relative to other Social Security beneficiaries. Additionally, substantial regional variation exists across states; employment rates ranged from 7 percent (West Virginia) to 23 percent (North Dakota). Moreover, we find that the employment rates among beneficiaries were sensitive to the business cycle and persistent over time.

Brain-derived neurotrophic factor (BDNF) has potential for the treatment of human neurodegenerative diseases. However, the general lack of success of neurotrophic factors in clinical trials has led to the suggestion that low molecular weight neurotrophic drugs may be better agents for therapeutic use. Here we describe small, dimeric peptides designed to mimic a pair of solvent-exposed loops important for the binding and activation of the BDNF receptor, trkB. The monomer components that make up the dimers were based on a monocyclic monomeric peptide mimic of a single loop of BDNF (loop 2) that we had previously shown to be an inhibitor of BDNF-mediated neuronal survival (O'Leary, P. D., and Hughes, R. A. (1998) J. Neurochem. 70, 1712-1721). Bicyclic dimeric peptides behaved as partial agonists with respect to BDNF, promoting the survival of embryonic chick sensory neurons in culture. We reasoned that the potency and/or efficacy of these compounds might be improved by reducing the conformational flexibility about their dimerizing linker. Thus, we designed a highly conformationally constrained tricyclic dimeric peptide and synthesized it using an efficient, quasi-one-pot approach. Although still a partial BDNF-like agonist, the tricyclic dimer was particularly potent in promoting neuronal survival in vitro (EC50 11 pm). The peptides described here, which are greatly reduced in size compared with the parent protein, could serve as useful lead compounds for the development of true neurotrophic drugs and indicate that the structure-based design approach could be used to obtain potent mimetics of other growth factors that dimerize their receptors.