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BackgroundGangstalking is a novel persecutory belief system whereby those affected believe they are being followed, stalked, and harassed by a large number of people, often numbering in the thousands. The harassment is experienced as an accretion of innumerable individually benign acts such as people clearing their throat, muttering under their breath, or giving dirty looks as they pass on the street. Individuals affected by this belief system congregate in online fora to seek support, share experiences, and interact with other like-minded individuals. Such people identify themselves as targeted individuals. ObjectiveThe objective of the study was to characterize the linguistic and rhetorical practices used by contributors to the gangstalking forum to construct, develop, and contest the gangstalking belief system. MethodsThis mixed methods study employed corpus linguistics, which involves using computational techniques to examine recurring linguistic patterns in large, digitized bodies of authentic language data. Discourse analysis is an approach to text analysis which focuses on the ways in which linguistic choices made by text creators contribute to particular functions and representations. We assembled a 225,000-word corpus of postings on a gangstalking support forum. We analyzed these data using keyword analysis, collocation analysis, and manual examination of concordances to identify discursive and rhetorical practices among self-identified targeted individuals. ResultsThe gangstalking forum served as a site of discursive contest between 2 opposing worldviews. One is that gangstalking is a widespread, insidious, and centrally coordinated system of persecution employing community members, figures of authority, and state actors. This was the dominant discourse in the study corpus. The opposing view is a medicalized discourse supporting gangstalking as a form of mental disorder. Contributors used linguistic practices such as presupposition, nominalization, and the use of specialized jargon to construct gangstalking as real and external to the individual affected. Although contributors generally rejected the notion that they were affected by mental disorder, in some instances, they did label others in the forum as impacted/affected by mental illness if their accounts if their accounts were deemed to be too extreme or bizarre. Those affected demonstrated a concern with accumulating evidence to prove their position to incredulous others. ConclusionsThe study found that contributors to the study corpus accomplished a number of tasks. They used linguistic practices to co-construct an internally coherent and systematized persecutory belief system. They advanced a position that gangstalking is real and contested the medicalizing discourse that gangstalking is a form of mental disorder. They supported one another by sharing similar experiences and providing encouragement and advice. Finally, they commiserated over the challenges of proving the existence of gangstalking.

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (inside-out (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.

Once upon a time, there was a girl named Purita and a boy named Nepo, and according to legend, they would be married three times: --once, in stuffy administrative offices [...]

As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines.

Author(s): Daniel Hunt [sup.1] , Maria Ioannou [sup.1] , John Synnott [sup.1] Author Affiliations: (1) grid.15751.37, 0000 0001 0719 6059, Department of Psychology, University of Huddersfield, , Queensgate, HD1 3DH, [...], When a child goes missing it is common practice to release an appeal of the child in the hope that a member of the public could help to identify and locate them. Despite being an everyday occurrence, there remains a significant gap in our understanding of how effective these appeals are. The present study sought to explore the effectiveness of missing children appeals through the recall accuracy of the general public immediately after observing the appeals and again after a three-day delay. One hundred and eighty-two participants observed either a mock Child Rescue Alert or a mock Twitter appeal. The results found no significant difference in recall accuracy between the design of the appeals although there was a significant difference in recall error. Confidence in own recall accuracy and the length of time spent observing the appeals were also found to be significantly associated with recall accuracy. Initial recall accuracy scores were significantly higher than recall accuracy scores following a three-day break. This exploratory study demonstrates the requirement to improve missing children appeals and lays the foundation for future studies to build on these findings further.

Background and objective Despite increasing urbanisation, little is known about skin health for urban-living Aboriginal children and young people (CYP, aged <18 years). This study aimed to investigate the primary care burden and clinical characteristics of skin conditions in this cohort. Methods A one-year retrospective cohort study of urban-living Aboriginal CYP presenting for general practitioner (GP) consultation at an Aboriginal Community Controlled Health Organisation (ACCHO) was conducted. Results At least one dermatological diagnosis was made in 27% (253/939) of GP face-to-face consultations for the 585 urban-living Aboriginal CYP included. Infections and dermatitis accounted for 54% (152/284) and 18% (50/284) of all dermatological diagnoses, respectively. Bacterial skin infection (BSI) cumulative incidence was 13% (74/585; 95% CI 10--16%), with recurrent BSI affecting <1% (5/585; 95% CI 0.3--2%) and hospitalisation required in 1% (1/82; 95% CI 0.06--7%) of incident BSI cases. Discussion We present a culturally secure, multidisciplinary skin health assessment model within an urban ACCHO, where dermatological conditions account for a significant proportion of GP workload. [ABSTRACT FROM AUTHOR]

BackgroundOveruse of clinical laboratory testing in the inpatient setting is a common problem. The objective of this project was to develop an inexpensive and easily implemented intervention to promote rational laboratory use without compromising resident education or patient care.MethodsThe study comprised of a cluster-randomized, controlled trial to assess the impact of a multifaceted intervention of education, guideline development, elimination of recurring laboratory orders, unbundling of laboratory panels, and redesign of the daily progress note on laboratory test ordering. The population included all patients hospitalized "general medicine" was duplicated during 2 consecutive months on a general medicine teaching service within a 999-bed tertiary care hospital in Boston, Massachusetts. The primary outcome was the total number of commonly used laboratory tests per patient day during 2 months in 2008. Secondary outcomes included a subgroup analysis of each individual test per patient day, adverse events, and resident and nursing satisfaction.ResultsA total of 5392 patient days were captured. The intervention produced a 9% decrease in aggregate laboratory use (rate ratio, 0.91; P = .021; 95% confidence interval, 0.84-0.98). Six instances of delayed diagnosis of acute kidney injury and 11 near misses were reported in the intervention arm.ConclusionsA bundled educational and administrative intervention promoting rational ordering of laboratory tests on a single academic general medicine service led to a modest but significant decrease in laboratory use. To our knowledge, this was the first study to examine the daily progress note as a tool to limit excessive test ordering. Unadjudicated near misses and possible harm were reported with this intervention. This finding warrants further study.

Have you ever seen a walrus fall from the sky? Forced to find space on a crowded melting glacier, the walrus scales steep ice cliffs. Unfortunately, they have poor depth [...]

PurposeRadiation Therapy Oncology Group 0321 is the first multi-institutional cooperative group high-dose-rate (HDR) prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity.Methods and materialsPatients are treated with external beam radiation therapy at 45 Gy and 1 HDR implant with 19 Gy in 2 fractions. Implants are done with transrectal ultrasound guidance, and computed tomography (CT)-compatible nonmetallic catheters. HDR planning is done on ≤3-mm-thick CT slices. The "mean DVH" (dose-volume histogram) of the planning target volume (PTV), implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation (SD) of the volume at 10-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters per implant, and patients per institution are calculated. Multivariate analysis and hazard ratios calculation of all the variables against reported grade ≥2 (G2+) genitourinary (GU) adverse events (Common Terminology Criteria for Adverse Events, version 3) are performed.ResultsDosimetry data are based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters per implant, and patients per institution are 54 cc, 63 cc, 19 and 9, respectively. The mean of %V100PTV, V80Bladder, V80Rectum, and V120Urethra were 94%, 0.40 cc, 0.15 cc, and 0.25 cc, respectively. There are too few G2+ gastrointestinal adverse event (GI AE) for correlative analysis; thus, the analysis has been performed on the more common G2+ GU AE. There are positive correlations noted between both acute and late G2+ GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2+ acute and late AE.ConclusionsHigher urethral dose, larger high-dose volumes, and lower dose homogeneity are associated with greater toxicities. A mean dose-volume histogram comparison at all dose levels should be used for quality control and future research comparison.

This article addresses the general ethical issues of accessing online personal data for research purposes. The authors discuss the practical aspects of online research with a specific case study that illustrates the ethical challenges encountered when accessing data from Kooth, an online youth web-counselling service. This paper firstly highlights the relevance of a process-based approach to ethics (Markham and Buchanan 2012 (See CR46)) when accessing highly sensitive data and then discusses the ethical considerations and potential challenges regarding the accessing of public data from Digital Mental Health (DMH) services. It presents solutions that aim to protect young DMH service users as well as the DMH providers and researchers mining such data. Special consideration is given to service users' expectations of what their data might be used for, as well as their perceptions of whether the data they post is public, private or open. We provide recommendations for planning and designing online research that includes vulnerable young people as research participants in an ethical manner. We emphasise the distinction between public, private and open data, which is crucial to comprehend the ethical challenges in accessing DMH data. Among our key recommendations, we foreground the need to consider a collaborative approach with the DMH providers while respecting service users' control over personal data, and we propose the implementation of digital solutions embedded within the platform for explicit opt-out/opt-in recruitment strategies and 'read more' options (Bergin and Harding 2016 (See CR9))., Author(s): Elvira Perez Vallejos [sup.1] , Ansgar Koene [sup.2] , Christopher James Carter [sup.3] , Daniel Hunt [sup.4] , Christopher Woodard [sup.5] , Lachlan Urquhart [sup.6] , Aislinn Bergin [sup.7] [...]

BackgroundThe objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes.MethodsThe phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA ≤0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure.ResultsFor 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30).ConclusionsThe current results indicated that failure to obtain a PSA-CR (PSA ≤0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation.

The solar thermochemical process of splitting CO2, known as CDS, is studied here using a redox cycle involving GeO2/GeO. The required thermodynamic data for a second-law-efficiency analysis is obtained from the HSC Chemistry software. The goal of this study is to investigate how different parameters, such as the operating temperatures and molar flow rate of the inert sweep gas, as well as the inclusion of separation units, heat exchangers, heaters, and coolers, can affect the solar-to-fuel energy conversion efficiency of the GeO2/GeO cycle. All calculations assume a constant gas-to-gas heat recovery effectiveness of 0.5. The analysis shows that the solar-to-fuel energy conversion efficiency is lower at a thermal reduction temperature of 1600 K (11.9%) compared to 2000 K. This is because high energy duties are required for heater-2, heater-3, and separator-1 due to the need for a higher inert gas flow rate. After conducting a comparative analysis of the three CDS cycles, it can be inferred that the GeO2/GeO cycle exhibits a significantly higher solar-to-fuel energy conversion efficiency in comparison to the ZnO/Zn and SnO2/SnO cycles across all thermal reduction temperatures. According to the comparison, it is confirmed that the GeO2/GeO CDS cycle can achieve a reasonably high solar-to-fuel energy conversion efficiency of 10% at less than 1600 K. On the other hand, ZnO/Zn and SnO2/SnO CDS cycles require a thermal reduction temperature of more than 1850 K to achieve a solar-to-fuel energy conversion efficiency of 10%. [ABSTRACT FROM AUTHOR]

Introduction Graft-versus-host disease (GVHD) represents a major cause of mortality after hematopoietic stem cell transplant (HCT) (1-4), and despite substantial effort, the control of GVHD remains one of the key [...], Controlling graft-versus-host disease (GVHD) remains a major unmet need in stem cell transplantation, and new, targeted therapies are being actively developed. CD28-CD80/86 costimulation blockade represents a promising strategy, but targeting CD80/CD86 with CTLA4-Ig may be associated with undesired blockade of coinhibitory pathways. In contrast, targeted blockade of CD28 exclusively inhibits T cell costimulation and may more potently prevent GVHD. Here, we investigated FR104, an antagonistic CD28-specific pegylated-Fab&apos;, in the nonhuman primate (NHP) GVHD model and completed a multiparameter interrogation comparing it with CTLA4-Ig, with and without sirolimus, including clinical, histopathologic, flow cytometric, and transcriptomic analyses. We document that FR104 monoprophylaxis and combined prophylaxis with FR104/sirolimus led to enhanced control of effector T cell proliferation and activation compared with the use of CTLA4-Ig or CTLA4- Ig/sirolimus. Importantly, FR104/sirolimus did not lead to a beneficial impact on Treg reconstitution or homeostasis, consistent with control of conventional T cell activation and IL-2 production needed to support Tregs. While FR104/sirolimus had a salutary effect on GVHD-free survival, overall survival was not improved, due to death in the absence of GVHD in several FR104/ sirolimus recipients in the setting of sepsis and a paralyzed INF-[gamma] response. These results therefore suggest that effectively deploying CD28 in the clinic will require close scrutiny of both the benefits and risks of extensively abrogating conventional T cell activation after transplant.