BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice

BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in Eμ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues.

Hydrologic and Water Quality Assessment of Miller Run: A Study of Bucknell University’s Impact

Human development causes degradation of stream ecosystems due to impacts on channel morphology, hydrology, and water quality. Urbanization, the second leading cause of stream impairment, increases the amount of impervious surface cover, thus reducing infiltration and increasing surface runoff of precipitation, which ultimately affects stream hydrologic process and aquatic biodiversity. The main objective of this study was to assess the overall health of Miller Run, a small tributary of the Bull Run and Susquehanna River watersheds, through an integrative hydrologic and water quality approach in order to determine the degree of Bucknell University’s impact on the stream. Hydrologic conditions, including stage and discharge, and water quality conditions, including total suspended solids, ion, nutrient, and dissolved metal concentrations, specific conductivity, pH, and temperature, were measured and evaluated at two sampling sites (upstream and downstream of Bucknell’s main campus) during various rain events from September 2007 to March 2008. The primary focus of the stream analysis was based on one main rain event on 26 February 2008. The results provided evidence that Miller Run is impacted by Bucknell’s campus. From a hydrologic perspective, the stream’s hydrograph showed the exact opposite pattern of what would be expected from a ‘normal’ stream. Miller run had a flashier downstream hydrograph and a broader upstream hydrograph, which was more than likely due to the increased amount of impervious surface cover throughout the downstream half of the watershed. From a water quality perspective, sediment loads increased at a faster rate and were significantly higher downstream compared to upstream. These elevated sediment concentrations were probably the combined result of sediment runoff from upstream and downstream construction sites that were being developed over the course of the study. Sodium, chloride, and potassium concentrations, in addition to specific conductivity, also significantly increased downstream of Bucknell’s campus due to the runoff of road salts. Calcium and magnesium concentrations did not appear to be impacted by urbanization, although they did demonstrate a significant dilution effect downstream. The downstream site was not directly affected by elevated nitrate concentrations; however, soluble reactive phosphorus concentrations tended to increase downstream and ammonium concentrations significantly peaked partway through the rain event downstream. These patterns suggest that Miller Run may be impacted by nutrient runoff from the golf course, athletic fields, and/or fertilizers applications on the main campus. Dissolved manganese and iron concentrations also appeared to slightly increase downstream, demonstrating the affect of urban runoff from roads and parking lots. pH and temperature both decreased farther downstream, but neither showed a significant impact of urbanization. More studies are necessary to determine how Miller Run responds to changes in season, climate, precipitation intensity, and land-use. This study represents the base-line analysis of Miller Run’s current hydrologic and water quality conditions; based on these initial findings, Bucknell should strongly consider modifications to improve storm water management practices and to reduce the campus’s overall impact on the stream in order to enhance and preserve the integrity of its natural water resources.

The Impact of Parental Psychological Control on College Students’ Relational Aggression and Friendship Quality

The present study investigated the relationships between parental psychological control and college students’ relational aggression and friendship quality. Based on previous research, it was expected that parents’ use of psychological control would be associated with students’ increased use of relational aggression with peers and lower friendship quality. Students completed a series of survey measures assessing their mothers’ and fathers’ use of psychological control, behavioral control, and warmth/acceptance. Students also completed a series of survey measures assessing their friendship quality, social skills, relational aggression, self-esteem, and social desirability. The study’s findings revealed that parental psychological control was associated with and predicted students’ increased use of relational aggression with peers. Parental psychological control was also associated with students’ lower friendship quality. However, parents’ use of psychological control did not predict students’ friendship quality after accounting for the influence of students’ personal and peer relationship variables. This finding suggests that characteristics of peer relationships may play a larger role than parenting behaviors in shaping college students’ friendships. The study also found that students who displayed higher levels of relational aggression had lower quality friendships. Other findings revealed that the relationship between parental psychological control and students’ friendship quality can be partially explained by students’ use of relational aggression with peers. Students’ friendship quality can also help to explain the influence of parental psychological control on students’ relational aggression. In addition, the study found that combinations of parenting behaviors were more informative predictors of students’ relational aggression and friendship quality than psychological control alone. Finally, this study revealed the importance of assessing participants’ social desirability when measuring sensitive personal qualities such as relational aggression, friendship quality, and self-esteem. Overall, this study contributes to the field of research on parental psychological control by revealing its effects on college students’ relational aggression and friendship quality.

Perinatal adaptation in mammals: the impact of metabolic rate

Mammalian birth is accompanied by profound changes in metabolic rate that can be described in terms of body size relationship (Kleiber's rule). Whereas the fetus, probably as an adaptation to the low intrauterine pO2, exhibits an "inappropriately" low, adult-like specific metabolic rate, the term neonate undergoes a rapid metabolic increase up to the level to be expected from body size. A similar, albeit slowed, "switching-on" of metabolic size allometry is found in human preterm neonates whereas animals that are normally born in a very immature state are able to retard or even suppress the postnatal metabolic increase in favor of weight gain and O2 supply. Moreover, small immature mammalian neonates exhibit a temporary oxyconforming behavior which enhances their hypoxia tolerance, yet is lost to the extent by which the size-adjusted metabolic rate is "locked" by increasing mitochondrial density. Beyond the perinatal period, there are no other deviations from metabolic size allometry among mammals except in hibernation where the temporary "switching-off" of Kleiber's rule is accompanied by a deep reduction in tissue pO2. This gives support to the hypothesis that the postnatal metabolic increase represents an "escape from oxygen" similar to the evolutionary roots of mitochondrial respiration, and that the overall increase in specific metabolic rate with decreasing size might contribute to prevent tissues from O2 toxicity.

Workfare Work: The Impact of Workfare on the Worker/Client Relationship

This article details the American experience of welfare reform, and specifically its experience instituting workfare programs for participants. In the United States, the term "welfare" is most commonly used to refer to the program for single mothers and their families, formerly called Aid to Families with Dependent Children (AFDC) and now, Temporary Assistance to Needy Families (TANF). In 1996, politicians "ended welfare as we know it" by fundamentally changing this program with the passage of the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA). The principal focus of the 1996 reform is mandatory work requirements enforced by sanctions and strict time limits on welfare receipt. While PRWORA's emphasis on work is not new, the difference is its significant ideological and policy commitment to employment, enforced by time limits. When welfare reform was enacted, some of its proponents recognized that welfare offices would have to change in order to develop individualized workfare plans, monitor progress, and impose sanctions. The "culture" of welfare offices had to be changed from being solely concerned with eligibility and compliance to individual, intensive casework. In this article, I will discuss how implementing workfare programs have influenced the relationship between clients and their workers at the welfare office. I start by describing the burdens faced by offices even before the enactment of welfare reform. Local welfare offices were expected to run programs that emphasized compliance and eligibility at the same time as workfare programs, which require intensive, personal case management. The next section of the paper will focus on strategies welfare offices and workers use to navigate these contradictory expectations. Lastly, I will present information on how clients react to workfare programs and some reasons they acquiesce to workfare contracts despite their unmet needs. I conclude with recommendations of how to make workfare truly work for welfare clients.

Impact of medications prescribed for treatment of attention-deficit hyperactivity disorder on physical growth in children and adolescents with HIV.

OBJECTIVE: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. METHODS: Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. RESULTS: Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). CONCLUSION: The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.

Perceived malleability of self versus the world and its impact on youths’ control orientation and well-being in the US, Germany, and India

Primary control is defined as changing the world to fit the self, while secondary control is defined as changing the self to fit the world. To understand why different individuals prefer different kinds of control processes, we proposed a research project looking at US, German and Indian young adults. We hypothesize that theories of self and the world (fixed vs. malleable; Dweck, 1999) affect the prevailing mode of control used. Furthermore, adolescents’ cultural background is assumed to affect their self-world theories as well as the adaptiveness of specific modes of control. For example, in the US, where the self is tended to be seen as fixed and the world as malleable, primary control prevails and is more adaptive than secondary control while the reverse is expected for India. We present the theoretical outline and methodology of the study as well as first results.

Introduction of a New Policy of no Nighttime Appendectomies: Impact on Appendiceal Perforation Rates and Postoperative Morbidity

Background Working hour limitations and tight health care budgets have posed significant challenges to emergency surgical services. Since 1 January 2010, surgical interventions at Berne University Hospital between 23:00 and 08:00 h have been restricted to patients with an expected serious adverse outcome if not operated on within 6 h. This study was designed to assess the safety of this new policy that restricts nighttime appendectomies (AEs). Methods The patients that underwent AE from 1 January 2010 to 31 December 2011 (“2010-2011 group”) were compared retrospectively with patients that underwent AE before introduction of the new policy (1 January 2006–31 December 2009; “2006-2009 group”). Results Overall, 390 patients were analyzed. There were 255 patients in the 2006–2009 group and 135 patients in the 2010–2011 group. Patients’ demographics did not differ statistically between the two study groups; however, 45.9 % of the 2006–2009 group and 18.5 % of the 2010–2011 group were operated between 23:00 and 08:00 h (p < 0.001). The rates of appendiceal perforations and surgical site infections did not differ statistically between the 2006–2009 group and the 2010–2011 group (20 vs. 18.5 %, p = 0.725 and 2 vs. 0 %, p = 0.102). Additionally, no difference was found for the hospital length of stay (3.9 ± 7.4 vs. 3.4 ± 6.0 days, p = 0.586). However, the proportion of patients with an in-hospital delay of >12 h was significantly greater in the 2010–2011 group than in the 2006–2009 group [55.6 vs. 43.5 %, p = 0.024, odds ratio (95 % confidence interval 1.62 (1.1–2.47)]. Conclusions Restricting AEs from 23:00 to 08:00 h does not increase the perforation rates and occurrence of clinical outcomes. Therefore, these results suggest that appendicitis may be managed safely in a semielective manner.

The impact of structural conditions in communes on sports behaviour of adolescents and young adults in Switzerland

Young peoples’ sport activity in Switzerland differs considerably depending on the linguistic region (Lamprecht, Fischer, & Stamm, 2008). This appears to be based on cultural as well as on structural differences. The question then arises how differing structural conditions in communes (e.g. sport facilities, significance of the municipal promotion of sport) across different linguistic regions of Switzerland cause variation in sport behaviour. Based on the theory of social action (Coleman, 1990), it is assumed that individual behaviour is not only determined by individual but also by structural and socio-cultural factors in which a person is socially embedded. In two case studies, multilevel data was gathered analysing possible influences of structural factors on sports behaviour. Using an online survey, 15 to 25 year old inhabitants (N = 205) living in a German and French speaking commune were questioned about their sports participation in and outside of their commune, as well as their perception of sport-related structural characteristics in their commune. To collect information about communes’ sport facilities, the sport providers (N = 23) were interviewed. Sport-related characteristics of the communes were also collected through two interviews with representatives of the municipal administration. As expected, sport participation is significantly lower in the French speaking commune (Chi2 (1, N = 205) = 3.84, p < .05). Adolescents and young adults living in the French speaking commune are less satisfied with the sport infrastructure (F(1,135) = 9.65, p < .01) and evaluate the opportunities to be physically active in their commune significantly worse (F(1,144) = 15.33, p < .01) than their German-speaking counterparts. These first findings show the impact of structural conditions in communes on sport participation of adolescents and young people. However, it must be noted that this study is explorative and further communes would need to be examined in order to generalize the results. References Coleman, J. S. (1990). Foundations of social theory. Cambridge, MA: Belknap. Lamprecht, M., Fischer, A. & Stamm, H. (2008). Sport Schweiz 2008. Das Sportverhalten der Schweizer Bevölkerung. Magglingen: BASPO.

Impact of development of job control and task-related stressors on resigned job attitude.

With more experience in the labor market, some job characteristics increase, some decrease. For example, among young employees who just entered the labor market, job control may initially be low but increase with more routine and experience. Job control is a job resource that is valued in itself and is positively associated with job satisfaction; but job control also helps dealing with stressors at work. There is little research on correlated changes, but the existing evidence suggests a joint development over time. However, even less is known about the relevance of such changes for employees. Usually, research tends to use mean levels to predict mean levels in outcomes but development in job control and stressors may be as relevant for job satisfaction as having a certain level in those job characteristics. Job satisfaction typically is regarded as a positive attitude towards one’s work. What has received less attention is that some employees may lower their expectations if their job situation does not reflect their needs, resulting in a resigned attitude towards one’s job. The present study investigates the development of job control and task-related stressors over ten years and tests the predictive value of changes in job control and task-related stressors for resigned attitude towards one’s job. We used data from a Swiss panel study (N=356) ranging over ten years. Job control, task-related stressors (an index consisting of time pressure, concentration demands, performance constraints, interruptions, and uncertainty about tasks), and resigned attitude towards one’s job were assessed in 1998, 1999, 2001, and 2008. Latent growth modeling revealed that growth rates of job control and task-related stressors were not correlated with one another. We predicted resigned attitude towards one’s job in 2008 a) by initial levels, and b) by changes in job control and stressors, controlling for resigned attitude in 1998. There was some prediction by initial levels (job control: β = -.15, p < .05; task-related stressors: β = .12, p = .06). However, as expected, changes in control and stressors predicted resigned attitude much better, with β = -.37, p < .001, for changes in job control, and β = .31, p < .001, for changes in task-related stressors. Our data confirm the importance of having low levels of task-related stressors and higher levels of job control for job attitudes. However, development in these job characteristics seems even more important than initial levels.

Cortical reorganisation of cerebral networks after childhood stroke: impact on outcome.

BACKGROUND Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.

Placental plasticity in monochorionic twins: Impact on birth weight and placental weight

INTRODUCTION The knowledge about adaptive mechanisms of monochorionic placentas to fulfill the demands of two instead of one fetus is largely speculative. The aim of our study was to investigate the impact of chorionicity on birth weight and placental weight in twin pregnancies. METHODS Forty Monochorionic (MC) and 43 dichorionic (DC) twin pregnancies were included in this retrospective study. Individual and total (sum of both twins) birth weights, placental weights ratios between placental and birth weights and observed-to-expected (O/E)-ratios were calculated and analyzed. Additionally, we investigated whether in twin pregnancies placental and birth weights follow the law of allometric metabolic scaling. RESULTS MC pregnancies showed higher placental O/E-ratios than DC ones (2.25 ± 0.85 versus 1.66 ± 0.61; p < 0.05), whereas the total neonatal birth weight O/E-ratios were not different. In DC twins total placental weights correlated significantly with gestational age (r = 0.74, p < 0.001), but not in MC twins. Analysis of deliveries ≤32 weeks revealed that the placenta to birth weight ratio in MC twins was higher than in matched DC twins (0.49 ± 0.3 versus 0.24 ± 0.03; p = 0.03). Allometric metabolic scaling revealed that dichorionic twin placentas scale with birth weight, while the monochorionic ones do not. DISCUSSION The weight of MC placentas compared to that of DC is not gestational age dependent in the third trimester. Therefore an early accelerated placental growth pattern has to be postulated which leads to an excess placental mass particularly below 32 weeks of gestation. The monochorionic twins do not follow allometric metabolic scaling principle making them more vulnerable to placental compromise.

Potential Impact of Sexual Transmission on Ebola Virus Epidemiology: Sierra Leone as a Case Study.

BACKGROUND Sexual transmission of Ebola virus disease (EVD) 6 months after onset of symptoms has been recently documented, and Ebola virus RNA has been detected in semen of survivors up to 9 months after onset of symptoms. As countries affected by the 2013-2015 epidemic in West Africa, by far the largest to date, are declared free of Ebola virus disease (EVD), it remains unclear what threat is posed by rare sexual transmission events that could arise from survivors. METHODOLOGY/PRINCIPAL FINDINGS We devised a compartmental mathematical model that includes sexual transmission from convalescent survivors: a SEICR (susceptible-exposed-infectious-convalescent-recovered) transmission model. We fitted the model to weekly incidence of EVD cases from the 2014-2015 epidemic in Sierra Leone. Sensitivity analyses and Monte Carlo simulations showed that a 0.1% per sex act transmission probability and a 3-month convalescent period (the two key unknown parameters of sexual transmission) create very few additional cases, but would extend the epidemic by 83 days [95% CI: 68-98 days] (p < 0.0001) on average. Strikingly, a 6-month convalescent period extended the average epidemic by 540 days (95% CI: 508-572 days), doubling the current length, despite an insignificant rise in the number of new cases generated. CONCLUSIONS/SIGNIFICANCE Our results show that reductions in the per sex act transmission probability via abstinence and condom use should reduce the number of sporadic sexual transmission events, but will not significantly reduce the epidemic size and may only minimally shorten the length of time the public health community must maintain response preparedness. While the number of infectious survivors is expected to greatly decline over the coming months, our results show that transmission events may still be expected for quite some time as each event results in a new potential cluster of non-sexual transmission. Precise measurement of the convalescent period is thus important for planning ongoing surveillance efforts.

Evaluating the impact of vertical integration on health system peformance

Vertical integration is grounded in economic theory as a corporate strategy for reducing cost and enhancing efficiency. There were three purposes for this dissertation. The first was to describe and understand vertical integration theory. The review of the economic theory established vertical integration as a corporate cost reduction strategy in response to environmental, structural and performance dimensions of the market. The second purpose was to examine vertical integration in the context of the health care industry, which has greater complexity, higher instability, and more unstable demand than other industries, although many of the same dimensions of the market supported a vertical integration strategy. Evidence on the performance of health systems after integration revealed mixed results. Because the market continues to be turbulent, hybrid non-owned integration in the form of alliances have increased to over 40% of urban hospitals. The third purpose of the study was to examine the application of vertical integration in health care and evaluate the effects. The case studied was an alliance formed between a community hospital and a tertiary medical center to facilitate vertical integration of oncology services while maintaining effectiveness and preserving access. The economic benefits for 1934 patients were evaluated in the delivery system before and after integration with a more detailed economic analysis of breast, lung, colon/rectal, and non-malignant cases. A regression analysis confirmed the relationship between the independent variables of age, sex, location of services, race, stage of disease, and diagnosis, and the dependent variable, cost. The results of the basic regression model, as well as the regression with first-order interaction terms, were statistically significant. The study shows that vertical integration at an intermediate health care system level has economic benefits. If the pre-integration oncology group had been treated in the post-integration model, the expected cost savings from integration would be 31.5%. Quality indicators used were access to health care services and research treatment protocols, and access was preserved in the integrated model. Using survival as a direct quality outcome measure, the survival of lung cancer patients was statistically the same before and after integration. ^

An evaluation of the impact of Inner City Development's Cooperative Home School: An educational alternative program to increase the quality and level of education in San Antonio's West Side community

The research study was intended to evaluate the effectiveness of Inner City Development's (I.C.D.) Cooperative Home School, an educational alternative program to the Title I public schools of San Antonio's West Side community. The study investigated students', parents' and tutors' perception of parental involvement and educational resources. The study also investigated each student's academic achievement. ^ The study found that students progressed toward expected math proficiency at a faster rate than they did in reading proficiency. However, because the target population size was small and a comparison group was not used, the results of this study are only suggestive. This research also indicated that study subjects believed students' quality and level of education increased substantially since program exposure. Study subjects mainly attributed the students' strides in academic performance to the increased amount of individualized attention students received in the small twelve-student class size. Study subjects were more satisfied with the home school's educational resources than those of the Title I public schools. Study subjects also perceived that parental involvement both at home and at school increased since enrollment in the home school program because: (1) there were more opportunities for involvement in the home school; and (2) parents felt closer to the tutors than the teachers in public school. ^ This evaluation also suggested improvements to program operations. With the help of additional volunteers, I.C.D. program operators could improve collection and organization of academic records. Furthermore, as suggested by program participants, science could be added to the curriculum. Lastly, a formal tutor orientation could be implemented to familiarize and train tutors on classroom management procedures. ^