Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV

We present a search for ZZ and ZW vector boson pair production in ppbar collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an integrated luminosity of 194 pb-1 collected with the Collider Detector at Fermilab, 3 candidate events are found with an expected background of 1.0 +/- 0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross section for ZZ plus ZW production, compared to the standard model prediction of 5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys. Rev. D Rapid Communication

Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.</p

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

Weed Management in 2050: Perspectives on the Future of Weed Science

The discipline of weed science is at a critical juncture. Decades of efficient chemical weed control have led to a rise in the number of herbicide-resistant weed populations, with few new herbicides with unique modes of action to counter this trend and often no economical alternatives to herbicides in large-acreage crops. At the same time, the world population is swelling, necessitating increased food production to feed an anticipated 9 billion people by the year 2050. Here, we consider these challenges along with emerging trends in technology and innovation that offer hope of providing sustainable weed management into the future. The emergence of natural product leads in discovery of new herbicides and biopesticides suggests that new modes of action can be discovered, while genetic engineering provides additional options for manipulating herbicide selectivity and creating entirely novel approaches to weed management. Advances in understanding plant pathogen interactions will contribute to developing new biological control agents, and insights into plant–plant interactions suggest that crops can be improved by manipulating their response to competition. Revolutions in computing power and automation have led to a nascent industry built on using machine vision and global positioning system information to distinguish weeds from crops and deliver precision weed control. These technologies open multiple possibilities for efficient weed management, whether through chemical or mechanical mechanisms. Information is also needed by growers to make good decisions, and will be delivered with unprecedented efficiency and specificity, potentially revolutionizing aspects of extension work. We consider that meeting the weed management needs of agriculture by 2050 and beyond is a challenge that requires commitment by funding agencies, researchers, and students to translate new technologies into durable weed management solutions. Integrating old and new weed management technologies into more diverse weed management systems based on a better understanding of weed biology and ecology can provide integrated weed management and resistance management strategies that will be more sustainable than the technologies that are now failing.WSSANational Institute of Food and AgricultureNIFA: 13599

Doctoral Supervision with Colleagues

The doctoral supervision of an academic colleague when both are employed in the same university has attracted limited research. In contrast, there is a plethora of research on a range of aspects related to doctoral supervision including processes associated with doctoral supervision, guidance for the doctoral supervisor, and the relationship between the doctoral supervisor and candidate. The completion of a doctorate is a substantial investment by both the candidate and the university and is brought into even sharper focus if the candidate is also an employee at the same university. Though each of the parties is driven by different agendas, they share a common interest in the successful completion of the doctorate. This may place additional pressure on the candidate and supervisor, particularly in relation to their professional credibility and career trajectory. This chapter draws from previous research conducted by the authors’ into this complex relationship and presents a number of recommendations to inform best practice. These recommendations have been drawn from the research participants, literature, and the authors’ experiences as doctoral candidates and doctoral supervisors for colleagues. The first section discusses important issues related to the area of colleague doctoral supervision. The following section identifies a series of recommendations concerning colleague doctoral supervision for the various stakeholders. The final section offers a blueprint for those tasked with formalizing this potential complex relationship