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Myotonic dystrophy type 1 (DM1) involves misregulated alternative splicing for specific genes. We used exon or nucleotide deletion to mimic altered splicing of genes central to muscle excitation- contraction coupling in mice. Mice with forced skipping of exon 29 in the [Ca.sub.V]1.1 calcium channel combined with loss of ClC-1 chloride channel function displayed markedly reduced lifespan, whereas other combinations of splicing mimics did not affect survival. The [Ca.sup.2+]/[Cl.sup.- ] bi- channelopathy mice exhibited myotonia, weakness, and impairment of mobility and respiration. Chronic administration of the calcium channel blocker verapamil rescued survival and improved force generation, myotonia, and respiratory function. These results suggest that [Ca.sup.2+]/[Cl.sup.-] bi-channelopathy contributes to muscle impairment in DM1 and is potentially mitigated by common clinically available calcium channel blockers., Introduction Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder characterized by myotonia, progressive weakness, heart block, gastrointestinal dysmotility, predisposition to malignancy, and other symptoms (1). Survival is limited [...]

Purpose: Alongside the inequities surfaced by COVID-19, a confluence of demographic and policy-related shifts over the last few decades has elevated the education of multilingual learners (MLs) in state education agency (SEA) leaders' work. This study employs an ecological perspective to examine how SEA leaders promote social justice policy implementation in their efforts to uphold MLs' civil rights under the Every Student Succeeds Act (ESSA). Research Methods: Given its embeddedness in a research-practice partnership (RPP) that emphasizes integration of researchers' expertise with SEA leaders' real-world knowledge, the study employs a participatory research approach. Drawing on 23 semistructured interviews with SEA leaders and 20 hours of observations during RPP meetings, the authors engaged in an iterative analysis process involving coding, memoing, and extensive member checking. Findings: Findings show the dual roles that leaders played to uphold the spirit of civil rights law across local education agencies (LEAs) and within SEAs, and they highlight the structural, cultural, and political dynamics that operated to enable or constrain this work. The study also reveals that cross-state collaboration may be a powerful mechanism for upholding ML civil rights in ways that go beyond compliance toward transformation and social justice. Implications: Although ESSA expanded the role of the SEA in policy implementation, little attention has been given to supporting state-level organizational development. Our findings suggest the need to allocate resources to support SEA capacity development. Such support is ever more critical as state systems work to develop coherent and aligned supports in response to COVID-19-related disparities.

For the past forty years, United States school districts have increasingly hired mathematics specialists to support the teaching and learning of mathematics. Despite the prevalence of this professional development structure, this is a relatively new research topic for the mathematics education field. In this paper, we report findings from an exploration of literature between 1981 and 2018 to examine the role of mathematics specialists (MSs). In particular, we examine: (1) MS positioning across research; (2) historical trends of school-based MS research; and (3) orientations of school-based MSs within research. Using the McGatha and Rigelman framework as an analytic lens, we found that beyond the positions identified in their framework (coach, intervention specialist, teacher), there were four additional MS positionings within the research (learner, other p-12 stakeholder, university stakeholder, unknown). Ultimately, we forward an expansion to the McGatha and Rigelman framework to include these new categories, as well as contextual descriptions and working definitions to support future research in more accurately and robustly capturing the ways in which MSs are investigated and reported on in research.

Following professional development (PD), implementation of contemporary topics into high school biology requires teachers to make critical decisions regarding integration of novel content into existing course scope and sequence. Often exciting topics, such as neuroscience, do not perfectly align with standards. Despite commitment to enacting what was learned in the PD, teachers must adapt novel content to their perceptions of good teaching, local context, prior knowledge of their students, and state and district expectations. How teachers decide to integrate curricula encountered from PD programs may affect student outcomes. This mixed-methods study examined the relationship between curricular application strategies following an inquiry-based neuroscience PD and student learning. Post-PD curricular implementation was measured qualitatively through analysis of teacher action plans and classroom observations and quantitatively using hierarchical linear modeling to determine the impact of implementation on student performance. Participation in neuroscience PD predicted improved student learning compared with control teachers. Of the two distinct curricular implementation strategies, enacting a full unit produced significantly greater student learning than integrating neuroscience activities into existing biology units. Insights from this analysis should inform teacher implementation of new curricula after PD on other contemporary biology topics.

Background Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease. Objectives The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing. Data sources The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment. Methods A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results. Results The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters. Limitations Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited. Conclusions Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only. Study registration This study is registered as PROSPERO CRD42021286891. Funding Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 10. See the NIHR Journals Library website for further project information. Plain language summary Non-alcoholic fatty liver disease includes a range of conditions that are caused by a build-up of fat in the liver, and not by alcohol consumption. This build-up of fat can cause inflammation. Persistent inflammation can cause scar tissue (fibrosis) to develop. It is important to identify patients with fibrosis because severe fibrosis can cause permanent liver damage (cirrhosis), which can lead to liver failure and liver cancer. In the National Health Service, patients with non-alcoholic fatty liver disease undergo tests to determine whether they have fibrosis. The test results are not always accurate and multiple tests can give conflicting results. Some of the tests may not be suitable for patients who have a very high body mass index. In the National Health Service, a liver biopsy may be offered to patients with inconclusive or conflicting test results or to those patients for whom other tests are unsuitable. However, liver biopsy is expensive, and is associated with side-effects such as pain and bleeding. Magnetic resonance imaging-based testing could be used as an extra test to help clinicians assess non-alcoholic fatty liver disease and identify patients who may need a liver biopsy. We assessed two magnetic resonance imaging-based diagnostic tests, LiverMultiScan and magnetic resonance elastography. LiverMultiScan is imaging software that is used alongside magnetic resonance imaging to measure markers of liver disease. Magnetic resonance elastography is used in some National Health Service centres to assess liver fibrosis; however, magnetic resonance elastography requires more equipment than just an magnetic resonance imaging scanner. We reviewed all studies examining how well LiverMultiScan and magnetic resonance elastography assess patients with non-alcoholic fatty liver disease. We also built an economic model to estimate the costs and benefits of using LiverMultiScan to identify patients who should be sent for a biopsy. Results from the model showed that LiverMultiScan may not provide good value for money to the National Health Service. Scientific summary Background Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a range of conditions caused by a build-up of fat in the liver that has not been caused by alcohol consumption. NAFLD covers a spectrum of histological lesions ranging from steatosis (simple fatty liver) to complex patterns of hepatocyte injury, inflammation and fibrosis. In the current National Health Service diagnostic pathway for staging fibrosis (based on guidelines and expert advice to NICE), patients with NAFLD (confirmed by ultrasound and liver aetiology screen) are referred for the fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS) or enhanced liver fibrosis (ELF) test as first-line testing. Patients with an indeterminate result from first-line testing are referred for second-line testing using transient elastography (TE), acoustic radiation force impulse (ARFI) or the ELF test, if it had not already been used as a first-line test. Patients with indeterminate or discordant results from fibrosis testing and patients with high risk of advanced fibrosis are considered for liver biopsy. Magnetic resonance imaging (MRI)-based testing could be used as an additional, non-invasive, diagnostic test to help clinicians stage NAFLD and potentially identify which patients should be referred for liver biopsy. Liver biopsy is expensive and is an invasive procedure that is associated with complications. Objectives The objectives of this study were to assess the diagnostic test accuracy (DTA), the clinical impact and the cost-effectiveness of two non-invasive MRI-based technologies, namely LiverMultiScan and magnetic resonance elastography (MRE), for patients with NAFLD for whom advanced fibrosis or cirrhosis had not yet been diagnosed and who had indeterminate results from fibrosis testing, for whom TE or ARFI was unsuitable, or who had discordant results from fibrosis testing. To achieve the study objectives, the External Assessment Group (EAG): conducted a systematic literature review to evaluate the (1) DTA of MRI-based technologies for the assessment of fibrosis, inflammation, and steatosis for a patients with NAFLD for whom advanced fibrosis or cirrhosis had not yet been diagnosed, using liver biopsy as the reference standard, and (2) the clinical impact of MRI-based technologies conducted a systematic literature review to explore the cost-effectiveness of MRI-based technologies as diagnostic tools and built a de novo economic model to assess the cost-effectiveness of two diagnostic pathways, namely MRI-based technologies plus biopsy and liver biopsy. Methods: assessment of diagnostic test accuracy and clinical impact Electronic databases (MEDLINE, MEDLINE Epub Ahead of Print In-Process & Other Non-Indexed Citations, Embase, Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database) were searched from inception to 4 October 2021. Eligible studies assessed the DTA or clinical impact of LiverMultiScan or MRE for patients with NAFLD for whom advanced fibrosis or cirrhosis had not yet been diagnosed (who have indeterminate results from fibrosis testing, for whom TE or ARFI is unsuitable, or who have discordant results from fibrosis testing). Two reviewers independently screened the titles and abstracts of all reports identified through electronic database searches and of all full-text articles subsequently obtained for assessment. Data extraction and quality assessment were conducted by one reviewer and checked for agreement by a second reviewer. The methodological quality of the included DTA studies was assessed using the QUality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The methodological quality of randomised controlled trials (RCTs) evaluating the clinical impact of MRI-based technologies was assessed using the Cochrane Risk of Bias 2.0 tool. The National Institute of Health study quality-assessment tools for cohort studies, case-control studies and before–after (pre-post) studies with no control group were used to assess risk of bias of included non-randomised studies. Qualitative studies were assessed using the Critical Appraisal Skills Programme (CASP) qualitative studies checklist. The sensitivity and specificity of each index test were summarised in forest plots. Where at least three studies provided both sensitivity and specificity data for a specific combination of index test, diagnosis of interest, and cut-off value, a bivariate random-effects meta-analysis to provide pooled estimates of sensitivity and specificity was considered. We did not perform bivariate meta-analyses where statistical heterogeneity between the studies (assessed by visually examining forest plots) was so great that pooled estimates of sensitivity and specificity would have been meaningless. Where at least three studies provided both sensitivity and specificity data for a specific combination of index test and diagnosis of interest, but used different cut-off values for the index test, we used a hierarchical model to estimate a summary receiver operating characteristic (ROC) curve. Methods: assessment of cost-effectiveness The EAG appended an economic evaluation-specific search filter to the clinical search strategies to identify published cost-effectiveness studies. In addition, two databases of economic publications [EconLit (EBSCO) and the cost-effectiveness analysis (CEA) registry] were searched from inception until 4 October 2021. The EAG developed a simple, flexible de novo model to estimate the cost-effectiveness of an MRI-based technologies plus biopsy pathway versus liver biopsy only pathway. Results The EAG searches of the electronic databases and reference lists of relevant studies and systematic reviews identified 4489 records (3331 unique records). Although all the identified studies for inclusion in the DTA, clinical impact and cost-effectiveness reviews included patients with NAFLD for whom advanced fibrosis or cirrhosis had not yet been diagnosed, only one study provided results for patients with NAFLD who had indeterminate or discordant results from fibrosis testing. No studies were identified that considered patients for whom TE or ARFI was unsuitable. Diagnostic test accuracy The EAG identified 13 studies (15 publications). Two studies (four publications) were evaluations of LiverMultiScan, 10 studies (10 publications) were evaluations of MRE, and one study (one publication) was an evaluation of LiverMultiScan and MRE. MRI-based technology: LiverMultiScan For the LiverMultiScan proton density fat fraction (PDFF) and LiverMultiScan iron-corrected T1 (cT1) outputs, 2 × 2 data were available from three studies. The EAG considers that the Eddowes 2018 study is the most relevant study to this assessment. Eddowes 2018 recruited patients who were scheduled for non-targeted liver biopsy to stage fibrosis after inconclusive non-invasive assessment of fibrosis or to make a diagnosis after a range of non-invasive tests had not confirmed a diagnosis. For diagnosis of fibrosis, estimates from Eddowes 2018 ranged from 50% to 88% for sensitivity and from 42% to 75% for specificity. Sensitivity and specificity values for fibrosis testing in Eddowes 2018 were consistently higher for LiverMultiScan cT1 than for LiverMultiScan PDFF. Data from three studies were included in the meta-analyses for LiverMultiScan. For advanced fibrosis (≥F3), the pooled sensitivity and specificity values were higher for LiverMultiScan cT1 [sensitivity = 60.2%, 95% confidence interval (CI): 50.9% to 68.8%; specificity = 65.4%, 95% CI 55.8% to 73.9%] than for LiverMultiScan PDFF (sensitivity = 38.6%, 95% CI 23.8% to 56.0%; specificity = 43.6%, 95% CI 30.7% to 57.5%). MRI-based technology: magnetic resonance elastography For the MRE test, 2 × 2 data were available from four studies. Estimates of sensitivity and specificity for advanced fibrosis (≥F3) were high and ranged from 71% to 100% and 79% to 93%, respectively. However, the cut-off values used to indicate a positive result from the index test varied between studies, therefore a summary ROC curve was estimated. The summary ROC curve indicates high DTA. However, observed study results do not all lie close to the summary ROC curve, which could be due to small sample sizes and/or clinical and methodological heterogeneity between the included studies. Clinical impact Eleven studies (14 publications) were included in the clinical impact review. Five studies (eight publications) were evaluations of LiverMultiScan and six studies (six publications) were evaluations of MRE. MRI-based technology: LiverMultiScan Two studies reported on the prognostic ability of LiverMultiScan cT1. However, neither study reported results specifically for the subpopulation of patients with NAFLD for whom advanced fibrosis or cirrhosis had not yet been diagnosed. One study reported that LiverMultiScan cT1 and LiverMultiScan PDFF could reduce the number of unnecessary biopsies for patients with non-NAFLD and NAFLD to diagnose non-alcoholic steatohepatitis (NASH) and fibrosis unrelated to NAFLD [EAG calculated odds ratio (OR) = 0.65, 95% CI 0.22 to 1.96] and for patients with no to mild fibrosis (F0 to F1) to diagnose significant fibrosis to cirrhosis (F2 to F4; EAG calculated OR = 0.59, 95% CI 0.18 to 1.89) when compared to standard of care. Three studies reported the test failure rate of LiverMultiScan for patients with all liver aetiologies. The test failure rate ranged from 5.3% to 7.6%. One study reported the test failure rate for LiverMultiScan for patients with NAFLD (5.6%). Acceptability of LiverMultiScan was reported in a qualitative study and was generally positive. MRI-based technology: magnetic resonance elastography Six studies reported the test failure rate of MRE for patients with all liver aetiologies. The test failure rate ranged from 0.0% to 7.6%. Three studies reported the test failure rate for MRE specifically for patients with NAFLD. The EAG performed a fixed-effects meta-analysis to obtain a pooled estimate of 4.2% (95% CI 2.5% to 6.2%) test failure rate for patients with NAFLD. Despite conducting additional targeted searches, the EAG did not identify any relevant studies that provided evidence of the clinical impact of MRI-based technologies for patients with NAFLD for whom advanced fibrosis or cirrhosis has not been diagnosed, for the remaining clinical impact outcomes listed in the final scope issued by NICE. Cost-effectiveness The EAG base-case incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained results for seven of the eight diagnostic test strategies considered, and showed that the LiverMultiScan plus biopsy pathway was dominated by the biopsy only pathway. For Brunt grade ≥2, the ICER per QALY gained was £1,266,511. Results from the EAG threshold and scenario analyses demonstrated that these results were robust to plausible variations in the magnitude of key parameters. Conclusions The DTA, clinical impact and cost-effectiveness data for MRI-based technologies are limited for patients who have indeterminate results from fibrosis testing, for whom TE or ARFI is unsuitable or patients who have discordant results from fibrosis testing. Only one small LiverMultiScan study provided DTA and population prevalence data for patients described in the final scope issued by NICE. It is unclear whether sensitivity and specificity estimates reported by this small study will give clinicians sufficient confidence to use LiverMultiScan test results to triage patients with inconclusive results from previous fibrosis testing to biopsy. Cost-effectiveness results from the EAG model are only informative if clinicians have confidence in LiverMultiScan DTA data. Using the available DTA and population prevalence data, EAG cost-effectiveness results showed that LiverMultiScan is unlikely to be cost-effective at current prices when used to triage patients with inconclusive results from previous fibrosis testing to biopsy. LiverMultiScan data are not available for patients for whom TE or ARFI was unsuitable. Further, no MRE DTA data were available for the population described in the final scope issued by NICE. The EAG was unable to generate cost-effectiveness results for this technology; however, even if MRE was 100% accurate, due to high population prevalence estimates it is unlikely that MRE would be cost-effective at current prices. Study registration This study is registered as PROSPERO CRD42021286891. Funding Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.

Objectives There are approximately 5.3 million informal carers in the United Kingdom, many of whom support family in their health despite being unpaid and often unsupported. Many visit pharmacies to collect medicines and look for advice. This work explores informal carer support within community pharmacies (CP). Methods Semi-structured video interviews exploring perspectives on the role of CP in supporting carers were conducted in autumn 2022. The study received institutional ethical approval. Interviews were audio-recorded, transcribed verbatim, and analysed using a reflexive thematic approach. Key findings In total 25 interviews were conducted with 13 carers and 12 pharmacy staff. Three themes were identified: -What support do carers need through CP?—medicines management, navigating services, and carers health and wellbeing. -Barriers to CP better supporting carers—relationships with CP, carer needs, identification as a 'carer'. -Enablers to CP better supporting carers—support is a team effort, and CP as a community 'hub'. Conclusions There is a trusted relationships between carers and pharmacy staff which can contribute to establishing pharmacies as a safe space of support, this includes medicines-specific support and navigating services, but also carer health and wellbeing support. Pharmacy staff may need to reconsider approaches to identifying and supporting carers and not just treating them as an extension of supporting a patient. In making this support accessible, relationships with pharmacy staff are important, as well as embracing CP as a 'community hub', although pharmacy staff may need training and information to facilitate them in this role. [ABSTRACT FROM AUTHOR]

Feathers incorporate circulating steroids during development. It is therefore assumed that the corticosterone (CORT) content of feathers ([CORT.sub.f]) represents an integrated measure of plasma CORT over the moult period. We tested this assumption by quantifying [CORT.sub.f] in feathers of House Sparrows (Passer domesticus (Linnaeus, 1758)) that were plucked before and after experimental manipulation of circulating CORT. Two of the seven flight feathers collected from each bird were fully grown throughout the CORT-manipulation period. We found that [CORT.sub.f] of all seven feathers corresponded with plasma CORT levels of non-moulting reference House Sparrows given the same implants. Surprisingly, the [CORT.sub.f] of the two mature feathers was 4- to 10-fold higher than values measured in the new replacement feathers. Our results show that [CORT.sub.f] of mature feathers may be affected by circulating CORT outside the moulting period. The most plausible explanation for our results is that CORT was transferred onto feather surfaces externally, but the mechanisms involved remain to be identified. Researchers are encouraged to establish effective procedures, in terms of both solvent and duration, for removing surface residues without extracting CORT from within the feather. This will increase confidence when inferring moult-related stress status from feather analyses in future ecological studies. Key words: feather, corticosterone, moult, glucocorticoid manipulation, mass spectrometry, House Sparrow, Passer domesticus. Les plumes incorporent des stéroïdes en circulation durant le développement. Il est donc présumé que la teneur en corticostérone (CORT) des plumes ([CORT.sub.f]) représente une mesure intégrée de la CORT plasmatique sur la durée de la période de mue. Nous avons vérifié cette hypothèse en quantifiant la [CORT.sub.f] dans des plumes de moineaux domestiques (Passer domesticus (Linnaeus, 1758)) prélevées avant et après une manipulation expérimentale de la CORT en circulation. La croissance de deux des sept pennes prélevées de chaque oiseau était terminée durant toute la période de manipulation de la CORT. Nous avons constaté que les [CORT.sub.f] des sept plumes correspondaient aux teneurs en CORT du plasma de moineaux domestiques témoins non en mue qui avaient reçu les mêmes implants. Etonnamment, les [CORT.sub.f] des deux pennes matures étaient de 4 à 10 fois plus grandes que les valeurs mesurées dans les nouvelles pennes. Nos résultats démontrent que la [CORT.sub.f] de plumes matures peut être influencée par la CORT en circulation en dehors dans la période de mue. L'explication la plus plausible de ces résultats est que de la CORT est transférée aux surfaces des plumes de manière externe, mais les mécanismes qui interviennent demeurent inconnus. Les chercheurs sont encouragés à établir des procédures concernant tant les solvants que la durée des manipulations visant à retirer les résidus superficiels sans extraire la CORT de l'intérieur des plumes. De telles procédures rehausseront le niveau de confiance d'estimations du stress associé à la mue basées sur l'analyse de plumes dans le cadre d'études écologiques futures. [Traduit par la Rédaction] Mots-clés : plume, corticostérone, mue, manipulation de glucocorticoïdes, spectrométrie de masse, moineau domestique, Passer domesticus., Introduction Corticosterone (CORT) is the main glucocorticoid hormone in birds and studies have shown that circulating CORT is incorporated into developing feathers via diffusion from the blood during cell differentiation [...]

Di-n-Butyl (DBP) and Di-(2-EthylHexyl) (DEHP) phthalates can leach from daily-use products resulting in environmental exposure. In male rodents, phthalate exposure results in reproductive effects. To evaluate effects on the immature primate testis, testis fragments from 6-month-old rhesus macaques were grafted subcutaneously to immune-deficient mice, which were exposed to 0, 10, or 500 mg/kg of DBP or DEHP for 14 weeks or 28 weeks (DBP only). DBP exposure reduced the expression of key steroidogenic genes, indicating that Leydig cell function was compromised. Exposure to 500 mg/kg impaired tubule formation and germ cell differentiation and reduced numbers of spermatogonia. Exposure to 10 mg/kg did not affect development, but reduced Sertoli cell number and resulted in increased expression of inhibin B. Exposure to DEHP for 14 week also affected steroidogenic genes expression. Therefore, long-term exposure to phthalate esters affected development and function of the primate testis in a time and dosage dependent manner.

Purpose: The purpose of this study is to explore patterns of importance ratings of managerial competencies in 22 countries in different regions around the globe, to guide specificity in assessing and developing managers in multiple geographies. Additionally, this study examined the utility of clustering countries based on shared culture, as defined by House "et al." (2004), to determine whether such clustering aids in interpreting and acting on any differences identified. Design/methodology/approach: The PROFILOR® for Managers contains 135 behavioral items, grouped into 24 competency scales. The instrument was developed from a review of the management and psychology literatures, exhaustive analysis of a large database (Sevy "et al.," 1985), job analysis questionnaires and interviews of hundreds of managers representing many functional areas and most major industries. Findings: Results suggest that clustering countries together for the purpose of providing prescriptive guidance for the development of individuals planning expatriate assignments does not clarify such guidance; in fact, it masks unique differences in competency priorities as measured on a country-by-country basis. Research limitations/implications: The participants for this study come from mid- to large-size organizations in 22 countries around the world. The organizations represented sought out management consulting services from a large, highly respected private-sector consultancy. As such, these findings are likely to be generalizable to managers from similar organizations. No attempt has been made to generalize these findings to entrepreneurial start-ups, small local organizations or organizations not inclined to seek Western-style management consulting services. Originality/value: This study is one of the first to examine the effectiveness of the GLOBE clusters as they relate to managerial competencies in multicultural workforces.