From aggressive to assertive

Aggressive behavior in men is seen as decisive, forceful, ambitious, and leader-like; it is often commended and even rewarded. Aggressive behavior in women is seen as hysterical, domineering, bitchy, and certainly not rewarded. Even assertive behavior in women is misunderstood to be aggressive. Both conscious and unconscious or implicit bias are at play. Although individual men are not responsible for these inequities, we all (men included) need to work to change our culture. Let’s agree that this double standard is unfair, and our workplaces need massive cultural change. This article is about how women can navigate through this double standard and still stand up for themselves. Published in an issue of International Journal of Women\u27s Dermatology on the topic of “The Gender Gap in Academic Dermatology and Dermatology Leadership: Problems and Solutions.

Building genomic infrastructure: Sequencing platinum-standard reference-quality genomes of all cetacean species.

International audienc

Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

Background: Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task. Methodology/Principal Findings: We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate. Conclusions/Significance: These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Population Ecology and Demography of an Endemic Subalpine Conifer (Pinus balfouriana) with a Disjunct Distribution in California

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Pathogens and insects in a pristine forest ecosystem: the Sierra San Pedro Martir, Baja, Mexico

We determined the incidence of pathogens and insects across mixed-conifer stands in the Sierra San Pedro Martir (SSPM) of northern Baja, Mexico, to assess the role of pests in a pristine forest ecosystem. We also determined the spatial distribution of the two most common pests, mistletoe, Phoradendron pauciflorum Torrey, and the fir engraver, Scolytus ventralis LeConte, of white fir (Abies concolor (Gord. & Glend.) Lindl.) across a 25-ha grid to assess spread and what host and pest variables were related. In these open parklike stands the mean tree density was 160 trees/ha, of which 58% were trees >20 cm diameter at breast height (DBH). In these low-density, mixed-aged stands we found that mixed-conifer species were well represented with no one species being completely dominant. Percent cumulative mortality for the SSPM was 12.7%, ranging from 2 to 24%, with the greatest amount of mortality occurring in the larger size classes, trees ³50 cm DBH. Multiple linear regression analysis showed that 78% of the mortality we observed was explained by pathogens and bark beetles (r2 = 0.78, P = 0.0001, F = 84). Mean pest incidence for Jeffrey pine (Pinus jeffreyi Grev. & Balf. in A. Murray), white fir, and sugar pine (Pinus lambertiana Dougl.) was 21, 88, and 2%, respectively. We found a number of relationships among host and pest variables, as well as a pathogen– insect interaction, and across the SSPM we found that nonhost species may be interfering in certain host–pest interactions. Spatial patterns from the 25-ha grid survey revealed that both P. pauciflorum and S. ventralis incidence were widespread. Phoradendron pauciflorum showed no spatial structure across the 25 ha but S. ventralis showed some degree of spatial structuring across the survey area. We also found that mistletoe severity was negatively correlated with regeneration of white fir. In pristine forests, pathogens and insects influence mortality and regeneration success, affecting stand structure and composition

Dwarf Mistletoe-host interactions in mixed-conifer forests in the Sierra Nevada

We determined the spatial pattern of dwarf mistletoe (Arceuthobium spp.) associated with two different conifer hosts, white fir (Abies concolor) and Jeffrey pine (Pinus jeffreyi), in forests around the Lake Tahoe Basin and at the Teakettle Experimental Forest, both located in the Sierra Nevada. We also examined a number of host variables and bark beetle incidence to determine how these factors might be involved in the Arceuthobium–conifer interaction. There was no significant relationship between dwarf mistletoe-infected trees and associated bark beetles. We found the highest incidence of dwarf mistletoe on Jeffrey pine in Lake Tahoe (87%), followed by dwarf mistletoe on white fir in Lake Tahoe (30%), with the lowest incidence on white fir at Teakettle (27%). Dwarf mistletoe incidence on white fir in our Lake Tahoe grid was not correlated to density but the dwarf mistletoe rating (DMR) was positively correlated to host size. At the Teakettle Forest, dwarf mistletoe incidence on white fir was not correlated with host density but the DMR was correlated with host size. Dwarf mistletoe incidence and DMR on Jeffrey pine were correlated with host density. Individuals, of both conifer species, in all diameter size classes were susceptible to dwarf mistletoe, with the lowest infection rate in the seedling-10-cm-diameter class. Arceuthobium on white fir in Lake Tahoe showed spatial dependence to a range of 20 m. However, Arceuthobium on Jeffrey pine in Lake Tahoe and on white fir at Teakettle showed no clear pattern of spatial structuring. The degree of infection and stand history appear to be important in the spatial dynamics of Arceuthobium spp.Keywords: Host-pathogen interactions, Disease dynamics, Spatial distributio