Sustaining productivity gains in the face of climate change: A research agenda for US wheat.

Wheat is a globally important crop and one of the "big three" US field crops. But unlike the other two (maize and soybean), in the United States its development is commercially unattractive, and so its breeding takes place primarily in public universities. Troublingly, the incentive structures within these universities may be hindering genetic improvement just as climate change is complicating breeding efforts. "Business as usual" in the US public wheat-breeding infrastructure may not sustain productivity increases. To address this concern, we held a multidisciplinary conference in which researchers from 12 US (public) universities and one European university shared the current state of knowledge in their disciplines, aired concerns, and proposed initiatives that could facilitate maintaining genetic improvement of wheat in the face of climate change. We discovered that climate-change-oriented breeding efforts are currently considered too risky and/or costly for most university wheat breeders to undertake, leading to a relative lack of breeding efforts that focus on abiotic stressors such as drought and heat. We hypothesize that this risk/cost burden can be reduced through the development of appropriate germplasm, relevant screening mechanisms, consistent germplasm characterization, and innovative models predicting the performance of germplasm under projected future climate conditions. However, doing so will require coordinated, longer-term, inter-regional efforts to generate phenotype data, and the modification of incentive structures to consistently reward such efforts.

The association between intraoperative cardiopulmonary bypass power and complications after cardiac surgery.

BACKGROUND: Low cardiac power (product of flow and pressure) has been shown to be associated with mortality in patients with cardiogenic shock after acute myocardial infarction, but has not been studied in cardiac surgical patients. This study's hypothesis was that cardiac power during cardiopulmonary bypass for cardiac surgery would have a greater association with adverse events than either flow or MAP (mean arterial pressure) alone. METHODS: We undertook a retrospective observational study using patient data from February 2015 to March 2022 undergoing cardiac surgery at Fiona Stanley Hospital in Perth Australia. Excluded were patient age less than 18 years old, patients undergoing thoracic transplantation, ventricular assist devices, off pump cardiac surgery and aortic surgery. The primary outcome was a composite outcome of 30-days mortality, stroke or new-onset renal insufficiency. RESULTS: Overall, 1984 cardiac surgeries were included in the analysis. Neither duration nor area below thresholds tested for power, MAP or flow was associated with the primary composite outcome. However, we found that an area below MAP thresholds 35-50 mmHg was associated with new renal insufficiency (adjusted odds ratio 1.17 [95% CI 1.02 to 1.35] for patients spending 10 min at 10 mmHg below 50 mmHg MAP compared to those who did not). CONCLUSIONS: This study suggests that MAP during cardiopulmonary bypass, but not power or flow, was an independent risk factor for adverse renal outcomes for cardiac surgical patients.

Reshaping Insanity in Pakistani Law: The Case of Safia Bano.

This Article analyzes the 2021 judgment of the Supreme Court of Pakistan in the case of Mst. Safia Bano v. Home Department, Government of Punjab. The case has garnered significant local and international attention due to the Court's ruling that a death sentence may not be carried out on a defendant who has a mental illness. Setting the case against the backdrop of Pakistan's Islamic and colonial contexts, this article argues that the Supreme Court has reshaped the insanity defense in Pakistani law by placing the determination of a defendant's mental state mainly in the hands of medical professionals. However, the Court's reliance on medical professionals and the subsequent downplaying of the "moral capacity" element of the insanity defense-a determination of law made by courts-has created an obstacle for courts to punish offenders more stringently in future cases due to the popular belief that mental health professionals are ill-equipped to answer broader questions of justice for victims and society. The article recommends that this issue can be remedied by establishing an objective legal test for insanity that considers Islamic law, Pakistani precedent, and advances in medical science.

When I Think of Home: Black Families Supporting Their Children During the COVID-19 Pandemic.

Since the onset of the COVID-19 pandemic, economic crisis, and persistent systemic and structural racism have plagued Black communities. The continued physical and symbolic violence and murders of Black bodies are undeniable. As White institutions, schools are definite contributors to this brutality as they center the culture and realities of White children while ignoring or denigrating Black children. This is even evident in the undermining of Black families' efforts to prepare their children to face the inequities and injustices they experience in the U.S. In this article, we discuss Black families' engagement in their children's education amid threats through racial socialization research aimed at developing and validating Black children's perspectives, experiences, and realities in Black identity to promote their positive social-emotional and psychological development. Black families must know how to cultivate their child's healthy self-identity, voice, and agency, along with academic achievement. Schools should learn from these practices. Schools that choose to ignore these concepts will continue contributing to trauma and violence against Black children and maintain deficit-oriented views. The article includes examples and implications for teaching and supporting the well-being of Black children, and concludes with practical ideas that educators can learn from and integrate into their practices.

Anatomy of resuscitative care unit: expanding the borders of traditional intensive care units.

Resuscitation lacks a place in the hospital to call its own. Specialised intensive care units, though excellent at providing longitudinal critical care, often lack the flexibility to adapt to fluctuating critical care needs. We offer the resuscitative care unit as a potential solution to ensure that patients receive appropriate care during the most critical hours of their illnesses. These units offer an infrastructure for resuscitation and can meet the changing needs of their institutions.

Common weight loss procedures and their complications.

BACKGROUND: As the number of obese patients in the United States continues to grow, there is a parallel increase in the number of bariatric surgery patients. A quarter of these patients will return to the Emergency Department (ED) within the first two years of the index procedure. OBJECTIVE: An understanding of the most common bariatric procedures and their related complications will greatly aide the Emergency Medicine physician in the care of these patients. DISCUSSION: Abdominal pain is the most common reason for bariatric patients to present to the ED and can represent a diagnostic challenge to EM physicians. It is important that EM physicians have a good understanding of bariatric procedures. We describe the three most common bariatric procedures: 1) the Laparoscopic Adjustable Gastric Banding (LAGB); 2) the Laparoscopic Sleeve Gastrectomy (LSG); 3) and the Roux-en-Y Gastric Bypass (RYGB). Due to the unique altered anatomy following the procedures there are specific complications related to each individual procedure. We will describe the most common presentations of abdominal pain in the post bariatric surgery patient. Finally, we will review new endoscopic procedures and the associated complications that may cause patients to present to the ED. CONCLUSION: Certain complications in bariatric surgery patients can have a high rate of morbidity and mortality. An improved understanding of bariatric procedures and their complications will allow for improved vigilance and management.

Correction: Correction to 'Clinical Policy: Critical Issues in the Evaluation of Adult Patients With Suspected Transient Ischemic Attack in the Emergency Department' [Annals of Emergency Medicine 68 (2016) 354-370.e29].

Due to a miscommunication during the process of transferring this manuscript from our editorial team to Production, the Members of the American College of Emergency Physicians Clinical Policies Committee (Oversight Committee) were not properly indexed in PubMed. This has now been corrected online. The publisher would like to apologize for any inconvenience caused.

Doing well while fighting river blindness: the alignment of a corporate drug donation programme with responsibilities to shareholders.

OBJECTIVE: Using the example of Merck's donations of ivermectin, to show how tax incentives and non-profit collaborators can make corporate largesse consistent with obligations to maximise returns to shareholders. METHODS: We obtained information from publicly available data and estimated Merck's tax deductions according to the US Internal Revenue Code. Reviews of Merck-Kitasato contracts and personal interviews provided additional information regarding key lessons from this collaboration. RESULTS: Our best estimate of the direct cost to Merck of the ivermectin tablets donated during 2005-2011 is around US$ 600 million, well below the stated value of US$ 3.8 billion. Our calculation of tax write-offs reduces the net cost to around US$ 180 million in that period. Indirect market benefits and effects on goodwill further enhanced the compatibility of Merck's donation programme with the company's profit-maximising objective. The case offers lessons for effective management of collaborations with public and non-profit organisations. CONCLUSION: Merck's role in the donation of ivermectin for the treatment of onchocerciasis is widely and justly acknowledged as a prime example of corporate largesse in the public interest. It is nevertheless important to note that several public and non-profit collaborators, and United States taxpayers, played significant roles in increasing Merck's incentives, and indeed ability, to conduct the donation programme that changed so many lives in poor countries, while meeting its responsibilities to shareholders. Overall, the record indicates responsible corporate management of Merck's ivermectin programme and demonstrates the feasibility of socially responsible policies in a manner compatible with obligations to shareholders.

Group 13 Superacid Adducts of [PCl2N]3.

Irrespective of the order of the addition of reagents, the reactions of [PCl2N]3 with MX3 (MX3 = AlCl3, AlBr3, GaCl3) in the presence of water or gaseous HX give the air- and light-sensitive superacid adducts [PCl2N]3·HMX4. The reactions are quantitative when HX is used. These reactions illustrate a Lewis acid/Brønsted acid dichotomy in which Lewis acid chemistry can become Brønsted acid chemistry in the presence of adventitious water or HX. The crystal structures of all three [PCl2N]3·HMX4 adducts show that protonation weakens the two P-N bonds that flank the protonated nitrogen atom. Variable-temperature NMR studies indicate that exchange in solution occurs in [PCl2N]3·HMX4, even at lower temperatures than those for [PCl2N]3·MX3. The fragility of [PCl2N]3·HMX4 at or near room temperature and in the presence of light suggests that such adducts are not involved directly as intermediates in the high-temperature ring-opening polymerization (ROP) of [PCl2N]3 to give [PCl2N]n. Attempts to catalyze or initiate the ROP of [PCl2N]3 with the addition of [PCl2N]3·HMX4 at room temperature or at 70 °C were not successful.

Successful Heart Transplant after Ten Hours Out-of-body Time using the TransMedics Organ Care System.

OBJECTIVE: We report the successful transplantation of a heart following an out-of-body time of 611 minutes into a recipient with dilated cardiomyopathy and left ventricular assist device implant. PATIENTS: Our patient was urgently waiting for a cardiac transplant whilst receiving LVAD support. Recurrent VF and repeated AICD shocks necessitated this action. RESULTS: Although requiring ECMO and inotropic support in the first 17 hours post-transplant, the patient was discharged from hospital on day 15 post-transplant with normal cardiac function. CONCLUSION: We report some of the salient points of the process and discuss the utility of this technology to an Australian transplant unit.

Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines.

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.

Evaluation of (89)Zr-pertuzumab in Breast cancer xenografts.

Pertuzumab is a monoclonal antibody that binds to HER2 and is used in combination with another HER2-specific monoclonal antibody, trastuzumab, for the treatment of HER2+ metastatic breast cancer. Pertuzumab binds to an HER2 binding site distinct from that of trastuzumab, and its affinity is enhanced when trastuzumab is present. We aim to exploit this enhanced affinity of pertuzumab for its HER2 binding epitope and adapt this antibody as a PET imaging agent by radiolabeling with (89)Zr to increase the sensitivity of HER2 detection in vivo. Here, we investigate the biodistribution of (89)Zr-pertuzumab in HER2-expressing BT-474 and HER2-nonexpressing MDA-MB-231 xenografts to quantitatively assess HER2 expression in vivo. In vitro cell binding studies were performed resulting in retained immunoreactivity and specificity for HER2-expressing cells. In vivo evaluation of (89)Zr-pertuzumab was conducted in severely combined immunodeficient mice, subcutaneously inoculated with BT-474 and MDA-MB-231 cells. (89)Zr-pertuzumab was systemically administered and imaged at 7 days postinjection (p.i.) followed by terminal biodistribution studies. Higher tumor uptake was observed in BT-474 compared to MDA-MB-231 xenografts with 47.5 ± 32.9 and 9.5 ± 1.7% ID/g, respectively at 7 days p.i (P = 0.0009) and blocking studies with excess unlabeled pertuzumab showed a 5-fold decrease in BT-474 tumor uptake (P = 0.0006), confirming the in vivo specificity of this radiotracer. Importantly, we observed that the tumor accumulation of (89)Zr-pertuzumab was increased in the presence of unlabeled trastuzumab, at 173 ± 74.5% ID/g (P = 0.01). Biodistribution studies correlate with PET imaging quantification using max SUV (r = 0.98, P = 0.01). Collectively, these results illustrate that (89)Zr-pertuzumab as a PET imaging agent may be beneficial for the quantitative and noninvasive assessment of HER2 expression in vivo especially for patients undergoing trastuzumab therapy.

Structure and conformation of the medium-sized chlorophosphazene rings.

Medium-sized cyclic oligomeric phosphazenes [PCl2N]m (where m = 5-9) that were prepared from the reaction of PCl5 and NH4Cl in refluxing chlorobenzene have been isolated by a combination of sublimation/extraction and column chromatography from the predominant products [PCl2N]3 and [PCl2N]4. The medium-sized rings [PCl2N]m have been characterized by electrospray ionization-mass spectroscopy (ESI-MS), their (31)P chemical shifts have been reassigned, and their T1 relaxation times have been obtained. Crystallographic data has been recollected for [PCl2N]5, and the crystal structures of [PCl2N]6, and [PCl2N]8 are reported. Halogen-bonding interactions were observed in all the crystal structures of cyclic [PCl2N]m (m = 3-5, 6, 8). The crystal structures of [P(OPh)2N]7 and [P(OPh)2N]8, which are derivatives of the respective [PCl2N]m, are also reported. Comparisons of the intermolecular forces and torsion angles of [PCl2N]8 and [P(OPh)2N]8 with those of three other octameric rings are described. The comparisons show that chlorophosphazenes should not be considered prototypical, in terms of solid-state structure, because of the strong influence of halogen bonding.

Branching Path Simulation for Pediatric Nurse Practitioner Students to Promote Critical Thinking: A Quasi-Experimental Study.

INTRODUCTION: Branching path simulation (BPS) is an active learning pedagogy incorporating gaming principles in a low-stakes, safe environment. No study has explored the use of BPS in advanced practice nursing education. This study measured pediatric nurse practitioner students' perception of the integration of BPS in one graduate-level course. METHOD: This study used a one group, post-test only quasi-experimental design with a convenience sample of 22 pediatric nurse practitioner students over 2 years enrolled in a university in the Pacific Northwest United States. RESULTS: Responses to BPS were positive: design (M = 4.8; SD ± 0.4), usability (M = 4.3; SD ± 1.0), self-confidence (M = 4.2; SD ± 0.8) and satisfaction (M = 4.8; SD ± 0.4). DISCUSSION: BPS was well received by learners. It not only provides immediate feedback and encourages students to identify their clinical management weaknesses and strengths but it also can be customized to needs in a course at a significant cost saving.

Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC.

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([89Zr]-panitumumab and [89Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors. HNSCC cells were treated with trastuzumab, cetuximab, or combination followed by radiation to assess for viability and radiosensitivity (colony forming assay, immunofluorescence, and flow cytometry). In vivo, [18F]-FMISO-PET imaging was used to quantify changes in oxygenation during treatment. Bliss Test of Synergy was used to identify combination treatment synergy. Quantifying EGFR and HER2 receptor expression revealed a 50% increase in heterogeneity of HER2 relative to EGFR. In vitro, dual trastuzumab-cetuximab therapy shows significant decreases in DNA damage response and increased response to radiation therapy (p < 0.05). In vivo, tumors treated with dual anti-HER2/EGFR demonstrated decreased tumor hypoxia, when compared to single agent therapies. Dual trastuzumab-cetuximab demonstrates synergy and can affect tumor oxygenation in HNSCC. Combination trastuzumab-cetuximab modulates the tumor microenvironment through reductions in tumor hypoxia and induces sustained treatment synergy.