An adjudicated hermeneutic single-case efficacy design study of experiential therapy for panic/phobia

This paper illustrates the application of an adjudicated form of Hermeneutic Single Case Efficacy Design (HSCED), a critical-reflective method for inferring change and therapeutic influence in single therapy cases. The client was a 61 year-old European-American male diagnosed with panic and bridge phobia. He was seen for 23 sessions of individual Process-Experiential/Emotion-Focused Therapy. In this study, affirmative and skeptic teams of researchers developed opposing arguments regarding whether the client changed over therapy and whether therapy was responsible for these changes. Three judges representing different theoretical orientations then assessed data and arguments, rendering judgments in favor of the affirmative side. We discuss clinical implications and recommendations for the future interpretive case study research

張州雑志の世界

Cities are increasingly exposed to extreme climate events such as floods and droughts. Land use change is also expected to reduce the availability of green spaces and intensify extreme heat events. Given these pressures on the quality of life of urban dwellers, there is a great need to improve the integrated management of water to enable sustainable development of rapidly growing cities and improve human well-being. A promising way to make urban communities more liveable is to invest in green water technologies, that is, decentralised and low-energy water supply, wastewater and stormwater solutions, to foster the transition to more sustainable and resilient cities. However, the adoption of multifunctional water technologies is a complex issue that requires cross-disciplinary approaches, demanding innovative thinking and practice. Despite the increasing body of literature on the benefits of decentralised water technologies, several barriers to their adoption remain. This paper uses an agent-based model that integrates social and environmental factors, as well as economic evaluation of water services provided by water technologies to assess the decision-making of two types of agents. The model is applied to evaluate incentive-based strategies to increase the adoption of rainwater tanks in Melbourne, a city that has suffered from severe droughts over the last decades. The model shows that using economic evaluation may not be adequate to understand the dynamics of rainwater tank uptake. Social factors such as public education might have played a role on decisions of households. This tool will be further tested and validated to explore policies and robust strategies to enable sustainable water management in rapidly developing cities.</p

The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes

Two-pore channels (TPCs) are localized in endo-lysosomal compartments and assumed to play an important role for vesicular fusion and endosomal trafficking. Recently, it has been shown that both TPC1 and 2 were required for host cell entry and pathogenicity of Ebola viruses. Here, we investigate the cellular function of TPC1 using protein toxins as model substrates for distinct endosomal processing routes. Toxin uptake and activation through early endosomes but not processing through other compartments were reduced in TPC1 knockout cells. Detailed co-localization studies with subcellular markers confirmed predominant localization of TPC1 to early and recycling endosomes. Proteomic analysis of native TPC1 channels finally identified direct interaction with a distinct set of syntaxins involved in fusion of intracellular vesicles. Together, our results demonstrate a general role of TPC1 for uptake and processing of proteins in early and recycling endosomes, likely by providing high local Ca2+ concentrations required for SNARE-mediated vesicle fusion

Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization

Inhibition in spinal nociceptive pathways is weaker and more labile in lamina I —where thermal input is primarily processed— than in lamina II that encodes predominantly high threshold mechanical input. This explains why noxious thermal input makes spinal circuits prone to catastrophic sensitization

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

Rationale and design of the Novel Uses of adaptive Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) pragmatic adaptive randomized trial: a trial protocol

Background: The prescribing of high-risk medications to older adults remains extremely common and results in potentially avoidable health consequences. Efforts to reduce prescribing have had limited success, in part because they have been sub-optimally timed, poorly designed, or not provided actionable information. Electronic health record (EHR)-based tools are commonly used but have had limited application in facilitating deprescribing in older adults. The objective is to determine whether designing EHR tools using behavioral science principles reduces inappropriate prescribing and clinical outcomes in older adults. Methods: The Novel Uses of Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) project uses a two-stage, 16-arm adaptive randomized pragmatic trial with a “pick-the-winner” design to identify the most effective of many potential EHR tools among primary care providers and their patients ≥ 65 years chronically using benzodiazepines, sedative hypnotic (“Z-drugs”), or anticholinergics in a large integrated delivery system. In stage 1, we randomized providers and their patients to usual care (n = 81 providers) or one of 15 EHR tools (n = 8 providers per arm) designed using behavioral principles including salience, choice architecture, or defaulting. After 6 months of follow-up, we will rank order the arms based upon their impact on the trial’s primary outcome (for both stages): reduction in inappropriate prescribing (via discontinuation or tapering). In stage 2, we will randomize (a) stage 1 usual care providers in a 1:1 ratio to one of the up to 5 most promising stage 1 interventions or continue usual care and (b) stage 1 providers in the unselected arms in a 1:1 ratio to one of the 5 most promising interventions or usual care. Secondary and tertiary outcomes include quantities of medication prescribed and utilized and clinically significant adverse outcomes. Discussion: Stage 1 launched in October 2020. We plan to complete stage 2 follow-up in December 2021. These results will advance understanding about how behavioral science can optimize EHR decision support to improve prescribing and health outcomes. Adaptive trials have rarely been used in implementation science, so these findings also provide insight into how trials in this field could be more efficiently conducted. Trial registration: Clinicaltrials.gov (NCT04284553, registered: February 26, 2020

Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer

Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions after a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes

Retention strategies among those on community supervision in the South: Lessons learned during the COVID-19 pandemic

OBJECTIVES: Cohort studies must implement effective retention strategies to produce internally valid and generalizable results. Ensuring all study participants are retained, particularly those involved in the criminal legal system, ensures study findings and future interventions will be relevant to this group, who are often lost to follow-up: critical to achieving health equity. Our objective was to characterize retention strategies and describe overall retention among an 18-month longitudinal cohort study of persons on community supervision prior to and during the COVID-19 pandemic. METHODS: We implemented various retention strategy best-practices (e.g., multiple forms of locator information, training study staff on rapport building, study-branded items). During the COVID-19 pandemic, we developed and describe new retention strategies. We calculated overall retention and analyzed differences between those retained and lost to follow-up by demographic characteristics. RESULTS: Prior to the start of the COVID-19 pandemic, 227 participants enrolled across three sites (N = 46 North Carolina; N = 99 Kentucky; N = 82 Florida). Of these, 180 completed the final 18-month visit, 15 were lost to follow-up, and 32 were ineligible. This resulted in an overall retention of 92.3% (180/195). While most participant characteristics did not differ by retention status, a greater proportion of those experiencing unstable housing were lost to follow-up. CONCLUSION: Our findings highlight that when retention strategies are flexible, particularly during a pandemic, high retention is still achievable. In addition to retention best-practices (e.g., frequent requests for updated locator information) we suggest other studies consider retention strategies beyond the study participant (e.g., paying participant contacts) and incentivize on-time study visit completion (e.g., providing a bonus when completed the study visit on time)

Knowledge, interest, and anticipated barriers of pre-exposure prophylaxis uptake and adherence among gay, bisexual, and men who have sex with men who are incarcerated

Criminal justice (CJ) settings disproportionately include populations at high risk for acquiring HIV, and CJ-involved individuals are often at the intersection of multiple overlapping risk factors. However, few studies have examined attitudes about pre-exposure prophylaxis (PrEP) among incarcerated men who have sex with men (MSM). This study explored interest in, knowledge of, and barriers to PrEP uptake among gay, bisexual, and other men who have sex with men at the Rhode Island Department of Corrections. Using semi-structured interviews, 26 MSM were interviewed about PrEP knowledge, interest, timing preferences for provision (e.g. before or after release), and barriers to uptake and adherence during community re-entry. Interviews were coded and analyzed using a general inductive approach. Participants demonstrated low initial knowledge of PrEP but high interest after being told more about it. Participants self-identified risk factors for HIV acquisition, including condom-less sex and substance use. In addition, participants preferred provision of PrEP prior to release. Post-release barriers to PrEP uptake and adherence included 1) concerns about costs of PrEP medications; 2) anticipated partner or family disapproval; 3) lack of access to transportation; 4) unstable housing; 5) compounding impacts of multiple hardships leading to a de-prioritization of PrEP and 6) fears of future re-incarceration. These results point to the need for future PrEP interventions among incarcerated populations that address incarceration and PrEP related barriers during community re-entry via wraparound services that address PrEP and incarceration-related barriers