Puerto Rico v. Franklin California Tax-Free Trust: Congressional Intent Interpreted Through a Plain Reading of the Federal Bankruptcy Code

In Puerto Rico v. Franklin California Tax-Free Trust, the Supreme Court held that Puerto Rico’s Recovery Act was pre-empted by federal law. While the Majority’s method of interpreting the plain language of the Bankruptcy Code was the correct course of action, additional notable interpretations and policy arguments were raised in regards to the Bankruptcy Code itself as well as this holding’s implications on the citizens of Puerto Rico. However, while Puerto Rico and the Dissent may not have found solace through the judiciary’s resolution in this matter, Congress’ swift passing of PROMESA has provided Puerto Rico with an initial opportunity to address its current financial situation

MICROCOMPUTER BUDGET MANAGEMENT SYSTEM

The enterprise budget, whole farm cash flow, and income statement are fundamental tools of farm and ranch management. The "Microcomputer Budget Management System" (MBMS) is a microcomputer software package that facilitates the storage and use of information for crop and livestock budgeting. It performs the calculations for several enterprise budgeting formats and for preparation of whole farm resource use reports and financial statements. The MBMS also includes internal machinery and irrigation cost calculation routines. MBMS was developed for use by extension staff, researchers, lenders, consultants, and operators of diversified farms and ranches with many enterprises that use enterprise and whole farm budgeting for analysis and planning activities. The flexibility and detailed nature of the program requires the user to have knowledge of enterprise budgeting and operation of complex computer programs. This paper presents a discussion of the features and capabilities of the software and the computational procedures used in the cost calculations.Research and Development/Tech Change/Emerging Technologies,

A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab

How are pay-for-performance schemes in healthcare designed in low- and middle-income countries? Typology and systematic literature review.

BACKGROUND: Pay for performance (P4P) schemes provide financial incentives to health workers or facilities based on the achievement of pre-specified performance targets and have been widely implemented in health systems across low and middle-income countries (LMICs). The growing evidence base on P4P highlights that (i) there is substantial variation in the effect of P4P schemes on outcomes and (ii) there appears to be heterogeneity in incentive design. Even though scheme design is likely a key determinant of scheme effectiveness, we currently lack systematic evidence on how P4P schemes are designed in LMICs. METHODS: We develop a typology to classify the design of P4P schemes in LMICs, which highlights different design features that are a priori likely to affect the behaviour of incentivised actors. We then use results from a systematic literature review to classify and describe the design of P4P schemes that have been evaluated in LMICs. To capture academic publications, Medline, Embase, and EconLit databases were searched. To include relevant grey literature, Google Scholar, Emerald Insight, and websites of the World Bank, WHO, Cordaid, Norad, DfID, USAID and PEPFAR were searched. RESULTS: We identify 41 different P4P schemes implemented in 29 LMICs. We find that there is substantial heterogeneity in the design of P4P schemes in LMICs and pinpoint precisely how scheme design varies across settings. Our results also highlight that incentive design is not adequately being reported on in the literature - with many studies failing to report key design features. CONCLUSIONS: We encourage authors to make a greater effort to report information on P4P scheme design in the future and suggest using the typology laid out in this paper as a starting point

Trials and tribulations: cross-learning from the practices of epidemiologists and economists in the evaluation of public health interventions.

The randomized controlled trial is commonly used by both epidemiologists and economists to test the effectiveness of public health interventions. Yet we have noticed differences in practice between the two disciplines. In this article, we propose that there are some underlying differences between the disciplines in the way trials are used, how they are conducted and how results from trials are reported and disseminated. We hypothesize that evidence-based public health could be strengthened by understanding these differences, harvesting best-practice across the disciplines and breaking down communication barriers between economists and epidemiologists who conduct trials of public health interventions

Assessing the contributions of childhood maltreatment subtypes and depression case-control status on telomere length reveals a specific role of physical neglect

Background: Studies have provided evidence that both childhood maltreatment and depressive disorders are associated with shortened telomere lengths. However, as childhood maltreatment is a risk factor for depression, it remains unclear whether this may be driving shortened telomere lengths observed amongst depressed patients. Furthermore, it's unclear if the effects of maltreatment on telomere length shortening are more pervasive amongst depressed patients relative to controls, and consequently whether biological ageing may contribute to depression's pathophysiology. The current study assesses the effects of childhood maltreatment, depression case/control status, and the interactive effect of both childhood maltreatment and depression case/control status on relative telomere length (RTL). Method: DNA samples from 80 depressed subjects and 100 control subjects were utilized from a U.K. sample (ages 20-84), with childhood trauma questionnaire data available for all participants. RTL was quantified using quantitative polymerase chain reactions. Univariate linear regression analyses were used to assess the effects of depression status, childhood maltreatment and depression by childhood maltreatment interactions on RTL. The false discovery rate (q 50 years old). There were no significant depression case/control status by childhood maltreatment interactions. Limitations: A relatively small sample limited our power to detect interaction effects, and we were unable to consider depression chronicity or recurrence. Conclusion: Shortened RTL was specifically associated with childhood physical neglect, but not the other subtypes of maltreatment or depression case/control status. Our results suggest that the telomere-eroding effects of physical neglect may represent a biological mechanism important in increasing risk for ageing-related disorders. As physical neglect is more frequent amongst depressed cases generally, it may also represent a confounding factor driving previous associations between shorter RTL and depression case status.Peer reviewe

Quantifying the effects of antibiotic treatment on the extracellular polymer network of antimicrobial resistant and sensitive biofilms using multiple particle tracking

Novel therapeutics designed to target the polymeric matrix of biofilms requires innovative techniques to accurately assess their efficacy. Here, multiple particle tracking (MPT) was developed to characterize the physical and mechanical properties of antimicrobial resistant (AMR) bacterial biofilms and to quantify the effects of antibiotic treatment. Studies employed nanoparticles (NPs) of varying charge and size (40–500 nm) in Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus (MRSA) biofilms and also in polymyxin B (PMB) treated Escherichia coli biofilms of PMB-sensitive (PMBSens) IR57 and PMB-resistant (PMBR) PN47 strains. NP size-dependent and strain-related differences in the diffusion coefficient values of biofilms were evident between PAO1 and MRSA. Dose-dependent treatment effects induced by PMB in PMBSens E. coli biofilms included increases in diffusion and creep compliance (P < 0.05), not evident in PMB treatment of PMBR E. coli biofilms. Our results highlight the ability of MPT to quantify the diffusion and mechanical effects of antibiotic therapies within the AMR biofilm matrix, offering a valuable tool for the pre-clinical screening of anti-biofilm therapies

Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones

The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics

Refining Expert Recommendations for Implementing Change (ERIC) strategy surveys using cognitive interviews with frontline providers

BACKGROUND: The Expert Recommendations for Implementing Change (ERIC) compilation includes 73 defined implementation strategies clustered into nine content areas. This taxonomy has been used to track implementation strategies over time using surveys. This study aimed to improve the ERIC survey using cognitive interviews with non-implementation scientist clinicians. METHODS: Starting in 2015, we developed and fielded annual ERIC surveys to evaluate liver care in the Veterans Health Administration (VA). We invited providers who had completed at least three surveys to participate in cognitive interviews (October 2020 to October 2021). Before the interviews, participants reviewed the complete 73-item ERIC survey and marked which strategies were unclear due to wording, conceptual confusion, or overlap with other strategies. They then engaged in semi-structured cognitive interviews to describe the experience of completing the survey and elaborate on which strategies required further clarification. RESULTS: Twelve VA providers completed surveys followed by cognitive interviews. The Engage Consumer and Support Clinicians clusters were rated most highly in terms of conceptual and wording clarity. In contrast, the Financial cluster had the most wording and conceptual confusion. The Adapt and Tailor to Context cluster strategies were considered to have the most redundancy. Providers outlined ways in which the strategies could be clearer in terms of wording (32%), conceptual clarity (51%), and clarifying the distinction between strategies (51%). CONCLUSIONS: Cognitive interviews with ERIC survey participants allowed us to identify and address issues with strategy wording, combine conceptually indistinct strategies, and disaggregate multi-barreled strategies. Improvements made to the ERIC survey based on these findings will ultimately assist VA and other institutions in designing, evaluating, and replicating quality improvement efforts

The ATG5-binding and coiled coil domains of ATG16L1 maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3 associated phagocytosis

Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells. We have investigated the roles played by autophagy and LAP in vivo by exploiting the observation that the WD domain of ATG16L1 is required for LAP, but not autophagy. Mice lacking the linker and WD domains, activate autophagy, but are deficient in LAP. The LAP −/- mice survive postnatal starvation, grow at the same rate as littermate controls, and are fertile. The liver, kidney, brain and muscle of these mice maintain levels of autophagy cargoes such as LC3 and SQSTM1/p62 similar to littermate controls, and prevent accumulation of SQSTM1 inclusions and tissue damage associated with loss of autophagy. The results suggest that autophagy maintains tissue homeostasis in mice independently of LC3-associated phagocytosis. Further deletion of glutamate E230 in the coiled-coil domain required for WIPI2 binding produced mice with defective autophagy that survived neonatal starvation. Analysis of brain lysates suggested that interactions between WIPI2 and ATG16L1 were less critical for autophagy in the brain, which may allow a low level of autophagy to overcome neonatal lethality. Abbreviations: CCD: coiled-coil domain; CYBB/NOX2: cytochrome b-245: beta polypeptide; GPT/ALT: glutamic pyruvic transaminase: soluble; LAP: LC3-associated phagocytosis; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; NOD: nucleotide-binding oligomerization domain; NADPH: nicotinamide adenine dinucleotide phosphate; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing Beclin 1-interacting protein; SLE: systemic lupus erythematosus; SQSTM1/p62: sequestosome 1; TLR: toll-like receptor; TMEM: transmembrane protein; TRIM: tripartite motif-containing protein; UVRAG: UV radiation resistance associated gene; WD: tryptophan-aspartic acid; WIPI: WD 40 repeat domain: phosphoinositide interacting