Carbonic Anhydrase Inhibitors Suppress Platelet Procoagulant Responses and In Vivo Thrombosis

Carbonic anhydrase (CA) inhibitors have a long history of safe clinical use as mild diuretics, in the treatment of glaucoma and for altitude sickness prevention. In this study, we aimed to determine if CA inhibition may be an alternative approach to control thrombosis. We utilized a high-resolution dynamic imaging approach to provide mechanistic evidence that CA inhibitors may be potent anti-procoagulant agents in vitro and effective anti-thrombotics in vivo. Acetazolamide and methazolamide, while sparing platelet secretion, attenuated intracellular chloride ion entry and suppressed the procoagulant response of activated platelets in vitro and thrombosis in vivo. The chemically similar N-methyl acetazolamide, which lacks CA inhibitory activity, did not affect platelet procoagulant response in vitro. Outputs from rotational thromboelastometry did not reflect changes in procoagulant activity and reveal the need for a suitable clinical test for procoagulant activity. Drugs specifically targeting procoagulant remodeling of activated platelets, by blockade of carbonic anhydrases, may provide a new way to control platelet-driven thrombosis without blocking essential platelet secretion responses

Association of perceived partner non-monogamy with prevalent and incident sexual concurrency

Concurrency is suggested as an important factor in sexually transmitted infection transmission and acquisition, though little is known regarding factors that may predict concurrency initiation. We examined the association between perception of a partner’s non-monogamy (PPNM) and simultaneous or subsequent concurrency among at-risk heterosexual young adults in the Los Angeles area

Factors affecting consistency and accuracy in identifying modern macroperforate planktonic foraminifera

Planktonic foraminifera are widely used in biostratigraphic, palaeoceanographic and evolutionary studies, but the strength of many study conclusions could be weakened if taxonomic identifications are not reproducible by different workers. In this study, to assess the relative importance of a range of possible reasons for among-worker disagreement in identification, 100 specimens of 26 species of macroperforate planktonic foraminifera were selected from a core-top site in the subtropical Pacific Ocean. Twenty-three scientists at different career stages – including some with only a few days experience of planktonic foraminifera – were asked to identify each specimen to species level, and to indicate their confidence in each identification. The participants were provided with a species list and had access to additional reference materials. We use generalised linear mixed-effects models to test the relevance of three sets of factors in identification accuracy: participant-level characteristics (including experience), species-level characteristics (including a participant’s knowledge of the species) and specimen-level characteristics (size, confidence in identification). The 19 less experienced scientists achieve a median accuracy of 57 %, which rises to 75 % for specimens they are confident in. For the 4 most experienced participants, overall accuracy is 79 %, rising to 93 % when they are confident. To obtain maximum comparability and ease of analysis, everyone used a standard microscope with only 35× magnification, and each specimen was studied in isolation. Consequently, these data provide a lower limit for an estimate of consistency. Importantly, participants could largely predict whether their identifications were correct or incorrect: their own assessments of specimen-level confidence and of their previous knowledge of species concepts were the strongest predictors of accuracy

Integrating science and society through long-term socio-ecological research

La investigación ecológica a largo plazo (Long Term Ecological Research, LTER) maneja problemas que abarcan décadas o plazos más largos. El programa y su nombre formal comenzaron en Estados Unidos en 1980. Si bien los estudios y observaciones a largo plazo comenzaron tempranamente en 1400 y 1800 en Asia y Europa, respectivamente, el enfoque a largo plazo no se formalizó sino hasta el establecimiento de los programas de investigación ecológica de largo plazo en Estados Unidos. Estos programas han permitido experimentos a nivel de ecosistemas y comparaciones entre sitios que condujeron a una mejor comprensión de la estructura y funcionamiento de la biosfera. El enfoque ecosistémico holístico de esta iniciativa permite también la incorporación de la dimensión humana en la ecología, y recientemente ha dado lugar al nuevo concepto de investigación socio-ecológica de largo plazo (LTSER). Hoy los programas de investigación socio-ecológica a largo plazo existen en por lo menos 32 países (esto es, los miembros de la Red Internacional de Investigación Ecológica a Largo Plazo o ILTER (International Long Term Ecological Research). Sin embargo, la consolidación de la red internacional dentro del paradigma de investigación socio-ecológica a largo plazo todavía requiere: (1) inclusión de algunas regiones remotas del mundo que aún están poco representadas, como el suroeste de América del Sur; (2) modificaciones en el tipo de investigación realizado, tales como la integración de las ciencias sociales y naturales con las humanidades y la ética, y (3) la incorporación de las conclusiones y resultados dentro de los procesos sociales y políticos. En este contexto, la naciente red de investigación socio-ecológica a largo plazo en Chile, que se extiende en el rango latitudinal más largo de bosque templado en el Hemisferio Sur, agrega una nueva región remota a las investigaciones ecológicas de largo plazo que había sido pasada por alto anteriormente. Además, la colaboración con la Universidad de North Texas y otros asociados internacionales ayuda a desarrollar un enfoque interdisciplinario para integrar las ciencias ecológicas y la filosofía ambiental, junto con los conocimientos ecológicos tradicionales, la educación informal y formal, la política, las humanidades, los procesos socio-políticos y la conservación biocultural.</jats:p

Functional Movement Screen Detected Asymmetry & Normative Values Among College-Aged Students

# Background The Functional Movement Screen (FMS™) is a popular test used by sports medicine professionals to identify dysfunctional movement patterns by analyzing mobility and stability during prescribed movements. Although the FMS™ has been a popular topic of research in recent years, normative data and asymmetries in college-aged students have not been established through research. # Purpose The objective was to determine normative FMS™ scores, report frequency counts for FMS™ asymmetries, and determine if the number of sports seasons and number of different sports an individual participated in during high school varied between university students that showed FMS™ identified asymmetries. # Study Design Cross-sectional Study # Methods One hundred university students completed the FMS™ and an associated survey to determine which sport(s) and for how many seasons they participated in each sport(s) during high school. Total FMS™ scores were assessed as well as identifying the presence of an asymmetry during a FMS™ screen. An asymmetry within the FMS™ was defined as achieving an unequal score on any of the screens that assessed right versus left movements of the body. # Data Analysis Data analysis included descriptive statistics, Pearson correlation was utilized to investigate the relationship between number of sports played and number of sport seasons. Shapiro Wilk test for normality, and Mann Whitney U test was employed to investigate group differences in number of sports played. All analyses were conducted using SPSS software. # Results Statistically significant correlations (r = .286, r^2^ = .08, p < 0.01) were found for both number of sport seasons and number of sports with FMS™ total score. In addition, participants without FMS™-detected asymmetries played significantly more seasons and more sports than their peers that presented asymmetries (U = 946.5, z = -1.98, p = 0.047). Finish with the actual p-value in parenthesis. # Conclusion Participating in multiple sports and multiple sport seasons during high school was associated with higher FMS™ total scores. Results suggest that participating in multiple sports and multiple sport seasons was associated with fewer asymmetries, which may decrease subsequent injury risk. # Level of Evidence 3

The 6dF Galaxy Survey: bulk flows on 50-70 h

We measure the bulk flow of the local Universe using the 6dF Galaxy Survey peculiar velocity sample (6dFGSv), the largest and most homogeneous peculiar velocity sample to date. 6dFGSv is a Fundamental Plane sample of ∼104 peculiar velocities covering the whole Southern hemisphere for galactic latitude |b| > 10°, out to redshift z = 0.0537. We apply the ‘minimum variance’ bulk flow weighting method, which allows us to make a robust measurement of the bulk flow on scales of 50 and 70 h−1 Mpc. We investigate and correct for potential bias due to the lognormal velocity uncertainties, and verify our method by constructing Λ cold dark matter (ΛCDM) 6dFGSv mock catalogues incorporating the survey selection function. For a hemisphere of radius 50 h−1 Mpc we find a bulk flow amplitude of U = 248 ± 58 km s−1 in the direction (l, b) = (318° ± 20°, 40° ± 13°), and for 70 h−1 Mpc we find U = 243 ± 58 km s−1, in the same direction. Our measurement gives us a constraint on σ8 of 1.01+1.07−0.58. Our results are in agreement with other recent measurements of the direction of the bulk flow, and our measured amplitude is consistent with a ΛCDM prediction

Comparing Breast Cancer Multiparameter Tests in the OPTIMA Prelim Trial: No Test Is More Equal Than the Others

Background: Previous reports identifying discordance between multiparameter tests at the individual patient level have been largely attributed to methodological shortcomings of multiple in silico studies. Comparisons between tests, when performed using actual diagnostic assays, have been predicted to demonstrate high degrees of concordance. OPTIMA prelim compared predicted risk stratification and subtype classification of different multiparameter tests performed directly on the same population. Methods: Three hundred thirteen women with early breast cancer were randomized to standard (chemotherapy and endocrine therapy) or test-directed (chemotherapy if Oncotype DX recurrence score &gt;25) treatment. Risk stratification was also determined with Prosigna (PAM50), MammaPrint, MammaTyper, NexCourse Breast (IHC4-AQUA), and conventional IHC4 (IHC4). Subtype classification was provided by Blueprint, MammaTyper, and Prosigna. Results: Oncotype DX predicted a higher proportion of tumors as low risk (82.1%, 95% confidence interval [CI] = 77.8% to 86.4%) than were predicted low/intermediate risk using Prosigna (65.5%, 95% CI = 60.1% to 70.9%), IHC4 (72.0%, 95% CI = 66.5% to 77.5%), MammaPrint (61.4%, 95% CI = 55.9% to 66.9%), or NexCourse Breast (61.6%, 95% CI = 55.8% to 67.4%). Strikingly, the five tests showed only modest agreement when dichotomizing results between high vs low/intermediate risk. Only 119 (39.4%) tumors were classified uniformly as either low/intermediate risk or high risk, and 183 (60.6%) were assigned to different risk categories by different tests, although 94 (31.1%) showed agreement between four of five tests. All three subtype tests assigned 59.5% to 62.4% of tumors to luminal A subtype, but only 121 (40.1%) were classified as luminal A by all three tests and only 58 (19.2%) were uniformly assigned as nonluminal A. Discordant subtyping was observed in 123 (40.7%) tumors. Conclusions: Existing evidence on the comparative prognostic information provided by different tests suggests that current multiparameter tests provide broadly equivalent risk information for the population of women with estrogen receptor (ER)–positive breast cancers. However, for the individual patient, tests may provide differing risk categorization and subtype information