Search

Large public accounting firms are currently prioritizing diversity and inclusion and making commitments to increased transparency by publishing diversity, equity, and inclusion reports. This case explores PwC’s self-described diversity and inclusion journey by juxtaposing the firm’s first publicly released diversity and inclusion report with the decades-earlier experience of Ann Hopkins, who became a partner as the result of a landmark Supreme Court case. This approach provides a longitudinal perspective on diversity and inclusion and facilitates analysis of the roles of organizational policies/procedures, organizational culture, and leadership in creating a more inclusive organization. The case presents an opportunity to analyze PwC’s published diversity data and explore the challenges firms face when trying to increase diversity and develop an inclusive culture.

Over the past few decades, there have been significant advances in male infertility, particularly in the development of novel diagnostic tools. Unfortunately, there remains a substantial number of patients that remain infertile despite these improvements. In this review, we take heed of the emerging technologies that will shape the future of male infertility diagnosis, evaluation, and treatment. Improvement in computer-assisted semen analyses and portability allow males to obtain basic semen parameters from the comfort of their home. Additionally, breakthrough ultrasound technology allows for preoperative prediction of potential areas of spermatogenesis within the testes, high-resolution optics permits better visualization during microdissection testicular sperm extraction (mTESE), and artificial intelligence improves sperm selection and identification.

PDF file - 1066KB, MEK inhibition alone and combination PI3K + MEK inhibition decreases serotonin secretion, while BEZ235 decreases CgA expression. (A) BON and (B) QGP-1 cells were plated in 24 well plates at a density of 1x105 cells/cm2. After 24h, cells were washed and maintained with serum-free medium. Cells were subsequently treated with either (upper panels) control, BKM120 (5 �M), PD0325901 (100 nM), or combination BKM120 + PD0325901 (5 �M/100 nM), or (lower panels) control, BEZ235 (1000 nM), PD0325901 (100 nM), or combination BEZ235 + PD0325901 (1000 nM/100 nM) for 1h. Media was collected and serotonin measured by serotonin ELISA (* p < 0.05 vs. control). (C) Whole cell lysates were collected following 24h of drug treatment with either control, BKM120 (5 �M), PD0325901 (100 nM), or combination BKM120 + PD0325901 (5 �M/100 nM), or control, BEZ235 (1000 nM), PD0325901 (100 nM), or combination BEZ235 + PD0325901 (1000 nM/100 nM) and analyzed for CgA expression. β-actin was used as a loading control.

PDF file - 649KB, Combination PI3K and MEK inhibitor treatment results in a more pronounced decrease in NCI-H727 and QGP-1 cell proliferation. (A) NCI-H727 and (B) QGP-1 cells were plated in 24 well plates at a density of 3x104 cells/well. Treatments were initiated the following morning with either control, BKM120 (5 μM), PD0325901 (100 nM), or combination BKM120 + PD0325901 (5 μM/100 nM) (upper panels), or control, BEZ235 (1000 nM), PD0325901 (100 nM), or combination BEZ235 + PD0325901 (1000 nM/100 nM) (lower panels). Media was exchanged for fresh drug media at 36h. Proliferation was assessed directly by cell counting at 72h (* p < 0.05 vs. control; � p < 0.05 vs. monotherapy).

PDF file - 812 KB, PI3K inhibition decreases cell proliferation in NCI-H727 and QGP-1 cell lines. (A) NCI-H727 and (B) QGP-1 cells were plated in 24 well plates at a density of 3x104 cells/well. Treatments were initiated the following morning with increasing doses of either BKM120 (0-5 μM) (upper panels) or BEZ235 (0-1000 nM) (lower panels). Media was exchanged for fresh drug media again at 36h. Proliferation was assessed directly by cell counting at 72h (* p < 0.05 vs. control). (C) BON cells transfected with shRNA directed against the alpha subunit of PI3K were plated in 24 well plates at a density of 3x104 cells/well and proliferation assessed at 24h intervals up to 96h.

PDF file - 741KB, PI3K inhibition enhances apoptosis in NCI-H727 and QGP-1 cell lines. (A) NCI-H727 and (B) QGP-1 cells were plated in 24 well plates at a density of 5x104 cells/cm2. Treatments were initiated the following morning with increasing doses of either BKM120 (0-5 μM) (upper panels) or BEZ235 (0-1000 nM) (lower panels) and continued for 24h. Apoptosis was measured by DNA fragmentation using the Cell Death Detection ELISAplus (* p < 0.05 vs. control).

Background: The precise involvement of the PI3K/mTOR and RAS/MEK pathways in carcinoid tumors is not well defined. Therefore, the purpose of our study was to evaluate the role these pathways play in carcinoid cell proliferation, apoptosis, and secretion and to determine the effects of combined treatment on carcinoid tumor inhibition.Methods: The human neuroendocrine cell lines BON (pancreatic carcinoid), NCI-H727 (lung carcinoid), and QGP-1 (somatostatinoma) were treated with either the pan-PI3K inhibitor, BKM120, or the dual PI3K–mTOR inhibitor, BEZ235, alone or in combination with the MEK inhibitor, PD0325901; proliferation, apoptosis, and protein expression were assessed. Peptide secretion was evaluated in BON and QGP-1 cells. The antiproliferative effect of BEZ235, alone or combined with PD0325901, was then tested in vivo.Results: Both BKM120 and BEZ235 decreased proliferation and increased apoptosis; combination with PD0325901 significantly enhanced the antineoplastic effects of either treatment alone. In contrast, neurotensin peptide secretion was markedly stimulated with BKM120 treatment, but not BEZ235. The combination of BEZ235 + PD0325901 significantly inhibited the growth of BON xenografts without systemic toxicity.Conclusions: Both BKM120 and BEZ235 effectively inhibited neuroendocrine tumor (NET) cell proliferation and stimulated apoptosis. However, inhibition of the PI3K pathway alone with BKM120 significantly stimulated neurotensin peptide secretion; this did not occur with the dual inhibition of both PI3K and mTOR using BEZ235 suggesting that this would be a more effective treatment regimen for NETs. Moreover, the combination of BEZ235 and the MEK inhibitor PD0325901 was a safe and more effective therapy in vivo compared with single agents alone. Clin Cancer Res; 20(5); 1212–22. ©2014 AACR.

PDF file - 1080KB, Combination PI3K + MEK inhibition enhances apoptosis compared to monotherapy. (A) NCI-H727 and (B) QGP-1 cells were plated in 24 well plates at a density of 5x104 cells/cm2. Treatments were initiated the following morning with either control, BKM120 (5 μM), PD0325901 (100 nM), or combination BKM120 + PD0325901 (5 μM/100 nM) (upper panels), or control, BEZ235 (1000 nM), PD0325901 (100 nM), or combination BEZ235 + PD0325901 (1000 nM/100 nM) (lower panels) and continued for 24 hours. Apoptosis was measured by DNA fragmentation using the Cell Death Detection ELISAplus (* p < 0.05 vs. control; � p < 0.05 vs. monotherapy). (C) BON cells were plated in 6 well plates at 9 x 105 cells/well. After 24h of treatment, cells were collected, stained with annexin V Alexa Fluor 488, and analyzed by flow cytometry (* p < 0.05 vs. control; � p < 0.05 vs. monotherapy).

PDF file - 1864KB, mTOR inhibition decreases proliferation but does not increase apoptosis or enhance effect in combination with a MEK inhibitor. (A) BON, (B) NCI-H727 and (C) QGP-1 cells were plated in 24 well plates at a density of 3x104 cells/well. Treatments were initiated the following morning with either control, rapamycin (20 nM), PIK-75 (1 μM), PD98059 (10 μM), rapaymycin + PD98059 (20 nM/10 μM), or PIK-75 + PD98059 (1 μM /10 μM). Proliferation (upper panels) was assessed directly by cell counting at 72h (* p < 0.05 vs. control; � p < 0.05 vs. monotherapy). Apoptosis (middle panels) was measured by DNA fragmentation using the Cell Death Detection ELISAplus (* p < 0.05 vs. control; � p < 0.05 vs. monotherapy). For Western blot analysis (lower panels), cells were plated in 6 well plates at a density of 5 x104 cells/cm2. Whole cell lysates were collected following 24h of drug treatment. β-actin was used as a loading control.

Background: Hypertensive disorders of pregnancy (HDPs) are a group of conditions that contribute to maternal morbidity and mortality, disproportionately affecting minority and low-income individuals. Complications from these HDPs may result in poor outcomes for mother and child during pregnancy or post-pregnancy. Disparities in HDPs may be associated with concentrated racial and income inequality in an individual’s activity space, such that the social exposure of places is not only formed by residence but also by daily mobility of the population at large. A novel aspect of women’s residential neighborhood environment can be explored by measuring daytime population mixing. Mobile phone data can be used to estimate social mixing during the daytime for income and racial/ethnic groups by describing the undercurrents of population mobility in neighborhoods. Objective: To estimate the association of daytime racial and income segregation with HDPs among women who gave birth from 2018 to 2019 in metro Atlanta. Methods: Data for women who gave birth in Metro Atlanta in 2018 and 2019 were abstracted from vital statistics records to determine HDP diagnosis and maternal residence by census tract. HDPs were grouped into pre-pregnancy hypertension, gestational hypertension, and eclampsia. Mobile phone location data from CUEBIQ were used to estimate median household income density in each census tract and racial/ethnic density, as a function of where devices moved between the hours of 7am and 10pm. Racial and economic composition of the device was assigned by the user’s estimated home census tract. The Index of Concentration at Extremes (ICE) was calculated as the mixing of mobile devices in each census tract, by race and income. Tracts were categorized as concentrated disadvantage for an ICE score less than -0.3 and concentrated privileged for an ICE score greater than 0.3. Logistic regression models were used to estimate odds of HDPs in census tracts with micro-segregation and income inequality during the daytime, compared to not at extremes. Results: There were 122,482 births included in the maternal cohort, and 8.1% of births occurred among women with a diagnosed HDP. Black women had a higher rate of HDPs compared to White women (9.7% versus 6.9%). Census tracts with higher daytime micro-segregation were associated with higher odds of HDPs compared to tracts not in the extremes (OR = 1.42; 95% CI= 1.35, 1.49). Census tracts with higher daytime income inequality were also associated with higher odds of HDPs (1.26;1.20, 1.33). Conclusions: The odds of maternal HDPs were higher among women in census tracts with greater racial daytime segregation and more income disparity, compared to tracts that were not identified as extremes. Describing and distinguishing social epidemiologic patterns for HDPs by population mobility may provide a better understanding of the social context of who is most at risk.

Management quality is known to influence depository institution performance, but less understood are the characteristics of managers that influence performance. We empirically examine how the political ideology of a credit union’s CEO influenced decision making and performance during the financial crisis. Our results indicate that the return on assets of credit unions run by conservative CEOs are 22 basis points lower during the crisis relative to liberal CEOs. Returns are shown to be lower as a direct result of credit unions with conservative CEOs applying more conservative accounting practices for loan losses than their counterparts during the crisis, despite similar loan quality.

Cellphones emit radiofrequency electromagnetic radiation (RF-EMR) for transmission of data for social media communication, web browsing, and music/podcast streaming. Use of Bluetooth ear buds has probably prolonged the time during which cellphones reside in the trouser pockets of men. It has been postulated that RF-EMR increases oxidative stress and induces free radical formation.To investigate the effect of wireless-spectrum (4G, 5G, and WiFi) RF-EMR emitted by modern smartphones on sperm motility and viability and explore whether these effects can be mitigated using a physical barrier or distance.Semen samples were obtained from fertile normozoospermic men aged 25-35 yr. A current-generation smartphone in talk mode was used as the RF-EMR source. A WhatsApp voice call was made using either 4G, 5G, or WiFi wireless connectivity. We determined if exposure effects were mitigated by either a cellphone case or greater distance from the semen sample.The semen samples were analyzed according to 2010 World Health Organization laboratory guidelines. Statistical analysis was performed using SPSS v.28.We observed decreases in sperm motility and viability with WiFi exposure but not with exposure to 4G or 5G RF-EMR. With large variability among smartphones, continued research on exposure effects is needed.Our exploratory study revealed that sperm motility and viability are negatively impacted by smartphones that use the WiFi spectrum for data transmission.We looked at the effect of cellphone use on sperm motility and viability. We found that cellphones using WiFi connectivity for data usage have harmful effects on semen quality in men.

Testosterone (T) plays an important role in male reproductive function and tissue development. Normal serum T levels vary between 300 and 1000 ng/dl. It is not known, however, if varying serum T levels alter androgen receptor (AR) signaling in tissue.To measure AR signaling levels in human corpus cavernosal tissue in males with different serum T levels.Participants were selected from a group of males undergoing surgical management for erectile dysfunction (ED; penile prosthesis placement). T levels were measured 1 week before surgery and a sample of corpus cavernosal tissue was procured during surgery. The tissue was homogenized, measured for protein concentration, and used for western blot analysis. VEGF was selected as an AR marker and actin was used for protein normalization.VEGF and actin expression levels were analyzed using western blot analysis and ImageJ was used for quantification of antibody expression.AR signaling was measured in terms of VEGF expression. Above a T level of 200 ng/dl, there was no significant difference found in VEGF expression. Only one patient had a T level less than 200 ng/dl, limiting the generalizability of these results. In addition, all patients had a history of ED, and controls (patients without ED) were not included in the study.Above a serum T level of 200 ng/dl, there was no significant difference in AR signaling. This finding suggests that there could be a saturation level present in corpus cavernosal tissue that is approximately 200 ng/dl.Serum testosterone levels above a certain threshold may not be necessary for biological functions. Instead, it is most likely that there is an approximate serum testosterone level that fully saturates tissue androgen receptors and results in peak function in men.

Purpose:The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome.Design and methods:Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings.Results:Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team’s open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team’s anticipation of parental emotional needs and provision of coping resources (p = 0.003).Conclusions:Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience.Practice implications:Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.

BACKGROUND Concerns have been raised about the consequences of the COVID‐19 pandemic on the mental health of adolescents during an important developmental and social period in their lives. This study examines the mental health impact of the pandemic on high school students shortly after closure of public schools in spring 2020, and whether this impact varies by sex, race/ethnicity, socioeconomic status (SES), and grade level. METHODS A cross‐sectional, one‐time online survey was completed by racial/ethnically and socioeconomically diverse students in 9th through 12th grade at 2 semi‐rural Georgia public high schools (N = 761). RESULTS Overall, almost one‐fourth of high school students were extremely or very worried about the pandemic, with higher rates of worry among students who are racial/ethnic minorities, lower SES, female and in older grades. Results indicated a concerning impact on the stress, anxiety, depression, and loneliness that students are feeling, particularly among girls and those in older grades. Students of color and low SES, who are already disproportionately impacted by COVID‐19, are also more likely to experience mental health challenges. CONCLUSIONS Findings highlight important demographic differences of the impact of COVID‐19 on the mental health of high school students and have implications for schools with addressing these needs.

Context: In long-term care (LTC), disturbed or inadequate sleep among older adult residents can exacerbate physical and cognitive conditions and decrease quality of life.Objectives: The quality improvement project sought to determine the feasibility and effectiveness of a multi-component environmental sleep toolkit designed to meet the needs of a LTC setting.Methods: The interdisciplinary project team conducted a needs assessment to determine the evidence-based interventions that were feasible for the setting. The team developed and implemented an environmental toolkit intervention, which sought to minimize sleep disruption from sound, light, routines, and diet. The team also provided staff education about sleep in older adults and the sleep environment.Findings: Post-intervention results showed improvement in overall sleep quality. Staff knowledge about sleep and the sleep environment was increased.Limitations: The toolkit interventions were relevant to a specific LTC residential setting, which may have implications for generalizability to other settings and facilities.Implications: Population-based environmental interventions are effective in improving sleep quality and life quality for older adults and are feasible for staff to implement and sustain.

Gpr126/Adgrg6 is an adhesion G protein-coupled receptor essential for Schwann cell (SC) myelination with important contributions to repair after nerve crush injury. Despite critical functions in myelinating SCs, the role of Gpr126 within nonmyelinating terminal Schwann cells (tSCs) at the neuromuscular junction (NMJ), is not known. tSCs have important functions in synaptic maintenance and reinnervation, and after injury tSCs extend cytoplasmic processes to guide regenerating axons to the denervated NMJ. In this study, we show that Gpr126 is expressed in tSCs, and that absence of Gpr126 in SCs (SC-specific Gpr126 knockout, cGpr126) results in a NMJ maintenance defect in the hindlimbs of aged mice, but not in young adult mice. After nerve transection and repair, cGpr126 mice display delayed NMJ reinnervation, altered tSC morphology with decreased S100β expression, and reduced tSC cytoplasmic process extensions. The immune response promoting reinnervation at the NMJ following nerve injury is also altered with decreased macrophage infiltration, Tnfα, and anomalous cytokine expression compared to NMJs of control mice. In addition, Vegfa expression is decreased in muscle, suggesting that cGpr126 non-cell autonomously modulates angiogenesis after nerve injury. In sum, cGpr126 mice demonstrated delayed NMJ reinnervation and decreased muscle mass following nerve transection and repair compared to control littermates. The integral function of Gpr126 in tSCs at the NMJ provides the framework for new therapeutic targets for neuromuscular disease.

Introduction Comprehensive, objective assessment of schools’ eating and physical activity environments is critical to developing and evaluating policies and interventions to reduce pediatric obesity inequities; however, few tools exist that describe the entire school comprehensively and are feasible with restricted resources. This study describes development and reliability of the observational school environment checklist (OSEC), a comprehensive observational audit tool. Method We developed the OSEC through iterative adaptations of existing instruments and pilot testing. The tool assesses four focus areas: cafeteria, lobby/hallway, gym, and outdoor areas. For reliability testing, two trained auditors independently completed the OSEC and met to resolve disagreements. For items with poor agreement, a third independent coder coded photographs taken during auditing. Percent agreement and Cohen’s kappa were calculated for all items and across four evidence-based constructs: atmosphere, accessibility, attractiveness, and advertising. Results After iterative development, the 88-item OSEC was tested for reliability in 18 schools. Items with poor (Implications The OSEC reliably and comprehensively captures the school environment. It requires few resources or expertise to administer, has acceptable reliability, and can assess atmosphere, accessibility, attractiveness, and advertising in school areas where students engage in eating and physical activity.

Background Mothers of young children from low-income communities may be vulnerable to barriers associated with low physical activity. The purpose of this study was to examine associations between home environment factors and maternal physical activity among mothers of toddlers. Methods Mothers of toddlers (n = 200) recruited from low-income communities simultaneously wore an ankle-placed accelerometer and were given a personal digital assistant for ecological momentary assessment. Mothers received randomly prompted questions about their current environment, activity, and social setting several times a day over eight consecutive days. Data were analyzed using linear mixed-effects regression models with random intercepts; within-group and between-group relations between physical activity and environment factors were disaggregated. Results Within-group relations included higher physical activity counts for specific mothers with television off versus on (95% CI = 130.45, 199.17), children absent versus present (95% CI = 82.00, 3.43), engaging with a child versus not (95% CI = 52.66, 127.63), and outside versus inside location (95% CI = 277.74, 392.67). Between-group relations included higher physical activity on average when other adults were absent versus present (95% CI = − 282.63, − 46.95). Recruitment site (urban vs. semi-urban) significantly moderated the within-group relation between being outside versus inside and activity count (β = − 243.12, 95% CI = − 358.74, − 127.47), and showed stronger relations among urban mothers (β = 440.33, 95% CI = 358.41, 522.25), than semi-urban (β = 190.37, 95% CI = 109.64, 271.11). Maternal body weight significantly moderated the within-group relation between being located outside versus inside the home and activity count (β for interaction = − 188.67, 95% CI = − 308.95, − 68.39), with a stronger relation among mothers with normal weight (β = 451.62, 95% CI = 345.51, 557.73), than mothers with overweight/obesity (β = 271.95, 95% CI = 204.26, 339.64). Conclusions This study highlights home environmental factors, including screen time, the presence of others (adults and children), and location (i.e., outside versus inside) that may relate to maternal physical activity behaviors. Understanding factors associated with physical activity could reduce physical activity disparities. Trial registry ClinicalTrials. NCT02615158, April 2006

The chapter examines the performance of Burns's songs in folk tradition drawing on two major sources of evidence: 'The Greig-Duncan Folk Song Collection' from Northeast Scotland and the Tobar an Dualchais/Kist o Riches website of archival audio recordings. It finds that Burns's songs could vary substantially from their original form as a result of the reworkings of folk tradition. In particular, the tune Burns desired was quite often not used once the song entered the tradition, with singers instead sometimes turning to something with which they were already familiar.

Objective To evaluate relationships between cycle threshold values and COVID-19 presentations and clinical courses in women presenting for childbirth. Cycle threshold values from polymerase chain reaction (PCR) testing are inversely proportional to viral burden and may be important predictors of disease state and infectivity risk. Design Retrospective cohort study Setting Three Yale-New Haven Health Hospitals between 4/2/2020-5/14/2020 Population Women presenting for childbirth who underwent SARS-CoV-2 PCR testing Methods Electronic health records were reviewed for socio-demographics, medical comorbidities, pregnancy and postpartum course, and COVID-19 symptoms and exposures. Records of SARS-CoV-2 positive women were reviewed for symptom onset, duration, and relation to test timing, disease course, and neonatal SARS-CoV-2 results. Main Outcome Measures SARS-CoV-2 real-time PCR cycle threshold values from positive tests were compared between asymptomatic and symptomatic women and in relation to disease severity. In women with symptomatic COVID-19, cycle threshold values were evaluated as a function of time since symptom onset. Results 1,210 women gave birth during the study period with 84 (6.9%) positive for SARS-CoV-2. Higher cycle threshold values were seen in asymptomatic SARS-CoV-2 positive patients (8/38 (21.1%) of asymptomatic women had cycle threshold

Aim This study explores the faculty perspective of an interprofessional clinical scholars program to identify recommendations for strengthening team collaboration between academia and clinical practice. Background Interprofessional evidence-based practice, pairing higher education and clinical practice, is a critical part of nursing education. Design This qualitative study consisted of two phases of participant engagement, in both data collection and data analysis. Methods Specifically, faculty participated in a focus group discussion followed by a card sort of initial codes. Results The major themes identified are Unifying the Team and Navigating Layers of Challenge, encompassing concepts of teamwork and programmatic context that supported or disrupted interprofessional collaboration. This study affirms the importance of role clarity, connectedness, intentionality and continuity within clinical teams. Moreover, faculty identified barriers to teamwork based on workload, leadership turnover and constraining environmental forces. Conclusions Recommendations for effective teamwork in an interprofessional setting will strengthen future collaboration between higher education and clinical settings.

Hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide, constituting one of the most significant causes of maternal morbidity and mortality. Hypertensive disorders, specifically gestational hypertension, chronic hypertension, and preeclampsia, throughout pregnancy are contributors to the top causes of maternal mortality in the United States. Diagnosis of hypertensive disorders throughout pregnancy is challenging, with many disorders often remaining unrecognized or poorly managed during and after pregnancy. Moreover, the research has identified a strong link between the prevalence of maternal hypertensive disorders and racial and ethnic disparities. Factors that influence the prevalence of maternal hypertensive disorders among racially and ethnically diverse women include maternal age, level of education, United States-born status, nonmetropolitan residence, prepregnancy obesity, excess weight gain during pregnancy, and gestational diabetes. Examination of the factors that increase the risk for maternal hypertensive disorders along with the current interventions utilized to manage hypertensive disorders will assist in the identification of gaps in prevention and treatment strategies and implications for future practice. Specific focus will be placed on disparities among racially and ethnically diverse women that increase the risk for maternal hypertensive disorders. This review will serve to promote the development of interventions and strategies that better address and prevent hypertensive disorders throughout a pregnant woman’s continuum of care.

Though we often “fear the worst”, worrying that unexpectedly bad things will happen, there are times when we “hope for the best”, imagining that unexpectedly good things will happen, too. The paper explores how the valence of the current situation influences people's imagining of unexpected future events when participants were instructed to think of “something unexpected”. In Experiment 1, participants (N = 127) were asked to report unexpected events to everyday scenarios under different instructional conditions (e.g., asked for “good” or “bad” unexpected events), and manifested a strong negativity bias in response to non-valenced instructions (i.e., being asked to “think of the unexpected” with no valence given). They mainly reported quite “predictable” unexpected outcomes that were negative; however, a post-test (N = 31) showed that the scenarios used were predominantly positive. In Experiment 2 (N = 257), when participants were instructed to think of “something unexpected and bizarre”, under the same instructional manipulations as Experiment 1, this negativity bias was replicated. In Experiment 3, using a design in which positive/negative materials were matched (verified by a pre-test, N = 60), it was found that when participants (N = 102) were given negative scenarios, they reported more positive events than they do when they are given positive scenarios. Though responding still retained an overwhelming negative bias, this result provided some evidence for a weaker valence-countering strategy; that is, where a negative scenario can lead to positive unexpected events being mentioned, and a positive scenario leads to negative unexpected events being reported. The implications of these results for people's projections of unexpected futures in their everyday lives is discussed.

Rationale: In cardiomyocytes, Na V 1.5 and Kir2.1 channels interact dynamically as part of membrane bound macromolecular complexes. Objective: The objective of this study was to test whether Na V 1.5 and Kir2.1 preassemble during early forward trafficking and travel together to common membrane microdomains. Methods and Results: In patch-clamp experiments, coexpression of trafficking-deficient mutants Kir2.1 Δ314-315 or Kir2.1 R44A/R46A with wild-type (WT) Na V 1.5 WT in heterologous cells reduced inward sodium current compared with Na V 1.5 WT alone or coexpressed with Kir2.1 WT . In cell surface biotinylation experiments, expression of Kir2.1 Δ314-315 reduced Na V 1.5 channel surface expression. Glycosylation analysis suggested that Na V 1.5 WT and Kir2.1 WT channels associate early in their biosynthetic pathway, and fluorescence recovery after photobleaching experiments demonstrated that coexpression with Kir2.1 increased cytoplasmic mobility of Na V 1.5 WT , and vice versa, whereas coexpression with Kir2.1 Δ314-315 reduced mobility of both channels. Viral gene transfer of Kir2.1 Δ314-315 in adult rat ventricular myocytes and human induced pluripotent stem cell–derived cardiomyocytes reduced inward rectifier potassium current and inward sodium current, maximum diastolic potential and action potential depolarization rate, and increased action potential duration. On immunostaining, the AP1 (adaptor protein complex 1) colocalized with Na V 1.5 WT and Kir2.1 WT within areas corresponding to t-tubules and intercalated discs. Like Kir2.1 WT , Na V 1.5 WT coimmunoprecipitated with AP1. Site-directed mutagenesis revealed that Na V 1.5 WT channels interact with AP1 through the Na V 1.5 Y1810 residue, suggesting that, like for Kir2.1 WT , AP1 can mark Na V 1.5 channels for incorporation into clathrin-coated vesicles at the trans -Golgi. Silencing the AP1 ϒ-adaptin subunit in human induced pluripotent stem cell–derived cardiomyocytes reduced inward rectifier potassium current, inward sodium current, and maximum diastolic potential and impaired rate-dependent action potential duration adaptation. Conclusions: The Na V 1.5-Kir2.1 macromolecular complex pre-assembles early in the forward trafficking pathway. Therefore, disruption of Kir2.1 trafficking in cardiomyocytes affects trafficking of Na V 1.5, which may have important implications in the mechanisms of arrhythmias in inheritable cardiac diseases.

We investigate the relation between managers’ personal ideologies and financial reporting quality. We use Federal Elections Commission data to develop three proxies for managers’ personal ideologies and test their relations with two financial reporting quality metrics: discretionary accruals and financial statement restatements. We find that both the absolute value of discretionary accruals and the probability of restatement decrease in the degree to which firms’ managers have conservative ideologies. These results are robust in the post-SOX period, to controls for potential self-selection bias, to alternative measures of both ideology and financial reporting quality, and to controls for firm political sensitivity, lobbying activity, governance, operational complexity and auditor strength. Our findings contribute to a growing literature demonstrating that business outcomes are partially explained by manager-specific factors including managers’ personal views and priorities.