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The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy.In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index.In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men.In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

During the COVID-19 pandemic, the Emory Ophthalmic Genetics Service (EOGS) adopted a hybrid telehealth-based care model, with patients undergoing a tailored panel of ancillary tests in addition to a video telehealth encounter with the EOGS physician. This study evaluates patient satisfaction with this model and effectiveness of these encounters in producing a clinical and genetic diagnosis.A trained interviewer administered a 14-question validated patient satisfaction survey to eligible subjects between October 2020 and April 2021. A mean "favorability index" for patient satisfaction was calculated (maximum score = 5). Rates of ancillary testing, completion of genetic testing, and diagnostic accuracy were also assessed, and compared to results from a control group of EOGS patients that underwent in-person visits.Twenty-one of 33 eligible patients completed the survey. Nine (42.9%) were female, with mean (± SD) age 51.3 ± 13.6 years. The control group was comprised of 49 subjects, predominantly female (71.4%), with mean age 51.5 ± 15.2 years. The mean (range) favorability index was 4.3 (3.1-5.0). Rates of ancillary testing were lower for the telemedicine group vs. the control group: 38.1% vs. 85.7% (Our results suggest high patient satisfaction and diagnostic accuracy with a hybrid telemedicine-based approach for IRD care, despite lower rates of ancillary testing and no in-person examination.

OBJECTIVE Children with complex chronic conditions (CCCs) and their parents benefit from supportive serious illness care when their conditions are severe and impact their quality of life and stress. This includes not only expert medical care but also effective relationships with the clinical team. Existing data suggest that there are opportunities for improvement. This study’s aim was to explore important aspects of the relationships and resources that facilitate supportive serious illness care among children with CCCs and their parents. METHODS We conducted semistructured interviews with adolescents and young adults (AYAs) with CCCs (aged 13–35 years), and parents of children with CCCs across 2 academic pediatric centers in the United States from December 2018 to April 2019. Transcripts were iteratively coded and analyzed by a team that included a sociologist, pediatric intensivist, and palliative care researcher by using inductive and deductive thematic analysis. RESULTS Seven AYAs with CCCs and 9 parents participated (16 total; 1 AYA–parent dyad). Two key categories were identified around relationships with the clinical team: trust and fostering collaboration. Three key categories related to resources are information needs, making sense of life with illness, and supportive community. Many of the key categories and themes identified by participants had both tangible and intangible components and revealed the distinct yet interconnected nature of these aspects of care. CONCLUSIONS Awareness and cultivation of relationship and resource support through innovative interventions and attention to those with increased needs in these areas may improve the serious illness care provided to children with CCCs and their parents.

OBJECTIVE Direct-to-consumer marketing has the potential to increase demand for specific treatments, but little is known about how to best market evidence-based psychotherapies to veterans with posttraumatic stress disorder (PTSD). The objective of this study was to gain an understanding of marketing messages that may impact veteran demand for prolonged exposure (PE) and cognitive processing therapy (CPT). METHOD Veterans (n = 31) with full or subthreshold PTSD participated in semistructured interviews that queried attitudes about PTSD and recovery, current knowledge of PE and CPT, and reactions to existing educational materials. A 2-stage qualitative coding and analytic strategy was used to identify primary themes related to the marketing of PE and CPT. RESULTS Veterans viewed the treatments' effectiveness as their primary selling point but questioned the credibility of improvement descriptions that didn't fit with their experiences or beliefs about PTSD. Participants had difficulties distinguishing CPT from non-trauma-focused approaches in which they had previously participated, leading to skepticism about promised treatment effects and decreased interest. Without targeting, women veterans assumed information regarding PTSD treatment options applied only to men. CONCLUSIONS Examination of the impact of a direct-to-consumer marketing campaign including these messages on PE and CPT demand is needed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The review examines the organization of specialized medical care for victims having burn injury in Primorsky Region. Thermal injury continues to occupy a significant place in the structure of domestic and industrial injuries in the Russian Federation. Every year, more than 300 calls about patients having thermal damage are received in Primorsky Region TCDM. For five years (from 2017 to 2021), specialists of the Primorsky TCDM made 178 visits to regional medical institutions, 160 seriously burned people were delivered to the specialized department by ground and air transport. There is still a need for round-the-clock collection of medical and sanitary information about the severely burned patients in medical institutions of Primorsky Territory and the organization of interaction with a specialized department. The Regional TCDM organized timely evacuation of patients having deep thermal traumas to the burn unit of FEDMC. It allowed performing surgical treatment tactics, including effective early removal of necrotic tissues. An analysis of appeals to the dispatcher's office of the Territorial Center for Disaster Medicine regarding severe thermal injury, as well as a statistical analysis of victims from remote areas of the Primorsky Territory delivered to the burn department in Vladivostok were conducted. It is emphasized that timely transportation of patients having severe burn injuries is the first step in the system of active treatment of victims which allows conducting early surgical treatment and reducing the number of complications, and improving treatment results.

PURPOSE Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality. METHODS CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and members of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. CIRS-G metrics were analyzed using Cox proportional hazards regression to determine subsequent mortality risk. RESULTS In total, 14,355 survivors with a median age of 24 (IQR, 18-30) years and 4,022 siblings with a median age of 26 (IQR, 19-33) years provided baseline data; 6,138 survivors and 1,801 siblings provided follow-up data. Cancer survivors had higher median baseline TS than siblings at baseline (5.75 v 3.44) and follow-up (7.76 v 4.79), all P < .01. The mean increase in TS from baseline to follow-up was significantly steeper in cancer survivors (2.89 males and 3.18 females) vs. siblings (1.79 males and 1.69 females) and NHANES population (2.0 males and 1.94 females), all P < .01. Every point increase in baseline TS increased hazard for death by 9% (95% CI, 8 to 10) among survivors. CONCLUSION Application of a geriatric rating scale to characterize disease supports the hypothesis that morbidity accumulation is accelerated in young adult survivors of childhood cancer when compared with siblings and the general population.

A machine learning (ML) design framework is proposed for adaptively adjusting clock frequency based on propagation delay of individual instructions. A random forest model is trained to classify propagation delays in real time, utilizing current operation type, current operands, and computation history as ML features. The trained model is implemented in Verilog as an additional pipeline stage within a baseline processor. The modified system is experimentally tested at the gate level in 45 nm CMOS technology, exhibiting a speedup of 70% and energy reduction of 30% with coarse-grained ML classification. A speedup of 89% is demonstrated with finer granularities with 15.5% reduction in energy consumption., 12 pages, 8 figures, 5 tables, IEEE transaction on computers. arXiv admin note: substantial text overlap with arXiv:2006.07450

Dermoscopy is a noninvasive technique that allows in vivo magnification of the skin structures and helps in visualizing microscopic features that are imperceptible to the naked eye. Dermoscopy is not a substitute for biopsy and histopathologic evaluation, but is an important tool that can help increase diagnostic sensitivity and specificity of cutaneous lesions. Dermoscopy increases the diagnostic sensitivity compared with naked eye examination. A significant improvement in diagnostic accuracy for benign and malignant lesions has been reported among family medicine physicians after an introductory training course on dermoscopy.

Supplementary Material 3. Codes used to identify colonoscopy procedures

Purpose: We assessed the association of quantitative clinical and pathologic information, including serum and tissue pro–prostate-specific antigen (proPSA) measurements, with outcomes among men with prostate cancer in an expectant management (active surveillance) program.Experimental Design: We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis: 39 subsequently developed unfavorable biopsies (Gleason score ≥7, ≥3 cores positive for cancer, >50% of any core involved with cancer), whereas 32 maintained favorable biopsies (median follow-up, 3.93 years). Serum total PSA, free PSA (fPSA), and [−2]proPSA were measured by the Beckman Coulter immunoassay. [−5/−7]proPSA was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion.Results: The ratio [−2]proPSA/% fPSA in serum was significantly higher at diagnosis (0.87 ± 0.44 versus 0.65 ± 0.36 pg/mL; P = 0.02) in men developing unfavorable biopsies. [−5/−7]proPSA tissue staining was more intense (4104.09 ± 3033.50 versus 2418.06 ± 1606.04; P = 0.03) and comprised a greater fractional area (11.58 ± 7.08% versus 6.88 ± 5.20%; P = 0.01) in BAA of these men. Serum [−2]proPSA/% fPSA [hazard ratio, 2.53 (1.18-5.41); P = 0.02], BAA [−5/−7]proPSA % area [hazard ratio, 1.06 (1.01-1.12); P = 0.02] and BAA [−5/−7]proPSA stain intensity [hazard ratio, 1.000213 (1.000071-1.000354); P = 0.003] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses. Serum [−2]proPSA/% fPSA significantly correlated with BAA [−5/−7]proPSA % area (ρ = 0.40; P = 0.002) and BAA [−5/−7]proPSA stain intensity (ρ = 0.33; P = 0.016).Conclusions: In a prospective cohort of men enrolled into expectant management for prostate cancer, serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment. The increase in serum proPSA/% fPSA might be driven by increased proPSA production from “premalignant” cells in the prostate BAA. (Clin Cancer Res 2009;15(23):7316–21)

Supplementary Material 4. Methods used to identify and adjust for reasons for not completing a colonoscopy.

Purpose: Analytically validated assays to interrogate biomarker status in clinical samples are crucial for personalized medicine. PTEN is a tumor suppressor commonly inactivated in prostate cancer that has been mechanistically linked to disease aggressiveness. Though deletion of PTEN, as detected by cumbersome FISH spot counting assays, is associated with poor prognosis, few studies have validated immunohistochemistry (IHC) assays to determine whether loss of PTEN protein is associated with unfavorable disease.Experimental Design: PTEN IHC was validated by employing formalin fixed and paraffin-embedded isogenic human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100% sensitive and 97.8% specific for detecting genomic alterations in 58 additional cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples, and PTEN FISH or high resolution single nucleotide polymorphism microarray analysis was done on a subset of these cases.Results: PTEN protein loss, as assessed as a dichotomous IHC variable, was highly reproducible, correlated strongly with adverse pathologic features (e.g., Gleason score and pathologic stage), detected between 75% and 86% of cases with PTEN genomic loss, and was found at times in the absence of apparent genomic loss. In a cohort of 217 high risk surgically treated patients, PTEN protein loss was associated with decreased time to metastasis.Conclusion: These studies validate a simple method to interrogate PTEN status in clinical specimens and support the utility of this test in future multicenter studies, clinical trials, and ultimately perhaps for routine clinical care. Clin Cancer Res; 17(20); 6563–73. ©2011 AACR.

Supplementary Table 2. Odds ratios and 95% confidence intervals for individual-level factors controlled for in the original and sensitivity-adjusted multivariate regression models for the 60-day and 6-month follow-up outcomes.

Supplementary Material 2. Organizational structure and process survey details

Purpose: Given discrepancies between preclinical and clinical observations of mammalian target of rapamycin (mTOR) inhibition in prostate cancer, we sought to determine the pharmacodynamic effects of the mTOR/TORC1 inhibitor rapamycin in men with intermediate- to high-risk prostate cancer undergoing radical prostatectomy.Experimental Design: Rapamycin was given at 3 or 6 mg orally for 14 days before radical prostatectomy in men with multifocal Gleason sum ≥7 prostate cancer; 10 untreated control subjects were included. The primary outcome was inhibition of phosphorylation of ribosomal S6 in posttreatment radical prostatectomy versus pretreatment biopsy tumor tissue, evaluated using a Simon two-stage design for pharmacodynamic efficacy.Results: Thirty-two subjects were accrued: 20 at 3 mg, 2 at 6 mg, and 10 controls. No dose-limiting toxicities were observed at 3 mg; however, two of two men enrolled at 6 mg experienced dose-limiting toxicities including thrombocytopenia and fever with grade 3 stomatitis. Adverse events observed at 3 mg included stomatitis, rash, ileus, and neutropenia. Pharmacodynamic studies showed tumor S6 phosphorylation inhibition in 50% of 10 evaluable rapamycin-treated men with sufficient paired tissue [median 58% inhibition (P = 0.049) versus 2% inhibition in controls (P = 0.75)] with no significant effect on AKT activity. We observed no change in Ki-67 or caspase-3 cleavage but noted a reduction in cytoplasmic p27 staining with increased nuclear localization with rapamycin treatment. Prostate tissue rapamycin concentrations were 3- to 4-fold higher than blood.Conclusions: At 3 mg daily, rapamycin successfully and safely inhibited prostate cancer S6 phosphorylation and achieved relatively high prostate tissue concentrations. No effect on AKT phosphorylation, tumor proliferation, or apoptosis was observed. Clin Cancer Res; 16(11); 3057–66. ©2010 AACR.

Purpose:Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown.Patients and Methods:We conducted a neoadjuvant, randomized study to quantify the immunologic effects of a GM-CSF–secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy.Results:Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T-cell infiltration and PD-L1 expression as compared with a cohort of untreated, matched controls. However, the CD8+ T-cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment, as well as an increase in PD-L1, there was no difference in the CD8+ T-cell infiltrate as compared with degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared with degarelix alone.Conclusions:Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer.

PDF file - 69KB, Correlation of PTEN protein status by immunohistochemistry (IHC) with PTEN genomic status by sequencing in NCI-60 cell line panel.

Figure S2

Supplementary Data from A Pharmacodynamic Study of Rapamycin in Men with Intermediate- to High-Risk Localized Prostate Cancer

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Figure S3

Supplementary Figure Captions

Background: This study assessed the contribution of organizational structures and processes identified from facility surveys to follow-up for positive fecal occult blood tests [FOBT-positive (FOBT+)].Methods: We identified 74,104 patients with FOBT+ results from 98 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011, and followed them until September 30, 2011, for completion of colonoscopy. We identified patient characteristics from VHA administrative records, and organizational factors from facility surveys completed by primary care and gastroenterology chiefs. We estimated predictors of colonoscopy completion within 60 days and six months using hierarchical logistic regression models.Results: Thirty percent of patients with FOBT+ results received colonoscopy within 60 days and 49% within six months. Having gastroenterology or laboratory staff notify gastroenterology providers directly about FOBT+ cases was a significant predictor of 60-day [odds ratio (OR), 1.85; P = 0.01] and six-month follow-up (OR, 1.25; P = 0.008). Additional predictors of 60-day follow-up included adequacy of colonoscopy appointment availability (OR, 1.43; P = 0.01) and frequent individual feedback to primary care providers about FOBT+ referral timeliness (OR, 1.79; P = 0.04). Additional predictors of six-month follow-up included using guideline-concordant surveillance intervals for low-risk adenomas (OR, 1.57; P = 0.01) and using group appointments and combined verbal–written methods for colonoscopy preparation instruction (OR, 1.48; P = 0.0001).Conclusion: Directly notifying gastroenterology providers about FOBT+ results, using guideline-concordant adenoma surveillance intervals, and using colonoscopy preparations instruction methods that provide both verbal and written information may increase overall follow-up rates. Enhancing follow-up within 60 days may require increased colonoscopy capacity and feedback to primary care providers.Impact: These findings may inform organizational-level interventions to improve FOBT+ follow-up. Cancer Epidemiol Biomarkers Prev; 24(2); 422–34. ©2014 AACR.

Supplementary Material 1. Codes used to identify FOBT procedures

Supplementary Table 1. Bivariate odds ratios and follow-up percentage estimates used for model building

Figure S1

Supplementary Tables 1-3, Figures 1-7 from Ligand-Independent Androgen Receptor Variants Derived from Splicing of Cryptic Exons Signify Hormone-Refractory Prostate Cancer

Protein-ligand docking is a computational method for identifying drug leads. The method is capable of narrowing a vast library of compounds down to a tractable size for downstream simulation or experimental testing and is widely used in drug discovery. While there has been progress in accelerating scoring of compounds with artificial intelligence, few works have bridged these successes back to the virtual screening community in terms of utility and forward-looking development. We demonstrate the power of high-speed ML models by scoring 1 billion molecules in under a day (50 k predictions per GPU seconds). We showcase a workflow for docking utilizing surrogate AI-based models as a pre-filter to a standard docking workflow. Our workflow is ten times faster at screening a library of compounds than the standard technique, with an error rate less than 0.01% of detecting the underlying best scoring 0.1% of compounds. Our analysis of the speedup explains that another order of magnitude speedup must come from model accuracy rather than computing speed. In order to drive another order of magnitude of acceleration, we share a benchmark dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million “in-stock” molecules over 15 receptors, or binding sites, across the SARS-CoV-2 proteome. We believe this is strong evidence for the community to begin focusing on improving the accuracy of surrogate models to improve the ability to screen massive compound libraries 100 × or even 1000 × faster than current techniques and reduce missing top hits. The technique outlined aims to be a fast drop-in replacement for docking for screening billion-scale molecular libraries.

Nearly all models of Earth’s oxygenation converge on the premise that the first notable rise of atmospheric oxygen occurred slightly above the Archean-Proterozoic boundary, with the second notable rise occurring just below the Proterozoic-Phanerozoic boundary. Plate tectonic–driven secular changes found above the Archean-Proterozoic boundary are thought to have been partly or wholly responsible for the initial rise in atmospheric O2 in the Great Oxidation Event; however, the role of plate tectonics in oxygen levels thereafter is not well defined. Modern plate tectonics undoubtedly play a role in regulating atmospheric O2 levels. Mountain building, for example, promotes high erosion rates, nutrient delivery to oceans, and efficient biogeochemical cycling of carbon, resulting in the net burial of organic carbon—thought to be the primary regulator of atmospheric O2 levels on geological time scales. The trajectory of atmospheric O2 and oceanic redox conditions in the Proterozoic Eon, representing almost 2 b.y. of geological history, shows a dynamic history with global trends that indicate overall high-low-high O2 levels throughout the Proterozoic Eon, with low-oxygen conditions established by ca. 2.0–1.8 Ga. This contravenes the tenet that major orogenic events (e.g., the Himalaya-scale Trans-Hudson orogen and other coeval orogens that formed the supercontinent Nuna) should yield higher O2 levels, not lower. The contrast of higher O2 early in the Paleoproterozoic with lower O2 later in the Paleoproterozoic is particularly striking, and mechanisms that might have caused this secular change remain unclear. This contribution explores feedbacks related to the tectonic evolution associated with the building of proto-Laurentia and Earth’s first supercontinent, Nuna, and how this impacted the trajectory of atmospheric O2 in the latest Paleoproterozoic Era.

Ambipolar carbon nanotube based field-effect transistors (AP-CNFETs) exhibit unique electrical characteristics, such as tri-state operation and bi-directionality, enabling systems with complex and reconfigurable computing. In this paper, AP-CNFETs are used to design a mixed-signal machine learning logistic regression classifier. The classifier is designed in SPICE with feature size of 15 nm and operates at 250 MHz. The system is demonstrated in SPICE based on MNIST digit dataset, yielding 90% accuracy and no accuracy degradation as compared with the classification of this dataset in Python. The system also exhibits lower power consumption and smaller physical size as compared with the state-of-the-art CMOS and memristor based mixed-signal classifiers.

A machine learning (ML) design framework is proposed for dynamically adjusting clock frequency based on propagation delay of individual instructions. A Random Forest model is trained to classify propagation delays in real-time, utilizing current operation type, current operands, and computation history as ML features. The trained model is implemented in Verilog as an additional pipeline stage within a baseline processor. The modified system is simulated at the gate-level in 45 nm CMOS technology, exhibiting a speed-up of 68% and energy reduction of 37% with coarse-grained ML classification. A speed-up of 95% is demonstrated with finer granularities at additional energy costs.

Research has established that individuals lower in self-control are at increased risk of offline criminal victimization due to their proclivity to engage in risky routine activities. While some studies have investigated whether a similar pattern is observed in the online context, additional inquiry into whether the link between low self-control and cybercrime victimization operates indirectly through risky online behavior is warranted given certain measurement and methodological limitations of prior research. Using original data collected on a sample of young adults, we find that the association between low self-control and a variety measure of cybercrime victimization operates entirely and indirectly through a variety measure of risky online behaviors. The implications of this finding for policy and programing are discussed.

Kidney transplant is superior to dialysis for the treatment of end-stage kidney disease, but accessing transplant requires high patient engagement to overcome barriers. We sought to develop an educational counselling intervention for patients along with their social support networks to help patients access the waiting list.Utilizing an Intervention Mapping approach, we established a conceptual framework to develop a behavioural intervention that can be reproduced across kidney transplant centres. The approach includes needs assessment, identifying behavioural determinants and process objectives and integrating targeted behavioural change theory.The Intervention Mapping process resulted in the development of a group counselling session, titled Journey to Transplant (JtT). This intervention was designed for kidney transplant candidates along with members of their social support networks and guided by a transplant healthcare professional. The session begins with standardized educational information to improve knowledge and normalize emotional barriers to transplant. This education is followed by a tailored counselling intervention, including the presentation of the individual patient's calculated likely outcomes on the kidney transplant waiting list. Finally, JtT incorporates patient and support network goal setting to address the specific barriers for that patient in accessing kidney transplantation.A systematic Intervention Mapping approach to develop the JtT intervention helps ensure the intervention is efficacious, acceptable and feasible for transplant centres to implement. JtT engages the patient's social support network, targeting known barriers to transplant and utilizing established behaviour change theory to motivate concrete actions to improve the likelihood of kidney transplantation.This study includes a patient and family advisory committee comprised of kidney transplant candidates and their family members to guide the final language and content of the intervention guide, and the conduct of the implementation and pilot testing of the intervention. However, patients and family members were not involved in the intervention mapping development process itself described in this manuscript, which was informed by focus group data from patient and family study participants.

Mixed-signal machine-learning classification has recently been demonstrated as an efficient alternative for classification with power expensive digital circuits. In this paper, a single-MOSFET analog multiplier is proposed for classifying high-dimensional input data into multi-class output space with less power and higher accuracy than state-of-the-art mixed-signal linear classifiers. A high-resolution (i.e., multi-bit) multiplication is facilitated within a single-MOSFET by feeding the features and feature weights into, respectively, the body and gate inputs. High-resolution classifier that considers the decisions of the individual predictors is designed at 180nm technology node and operates at 100MHz in near/subthreshold region. To evaluate the performance of the classifier, a reduced MNIST dataset is generated by downsampling the MNIST digit images from 784 features to 48 features. The system is simulated across a wide range of PVT variations, exhibiting average accuracy of 92% (2% improvement over state-of-the-art), energy consumption of 67.3 pJ per classification (over 8 times lower than state-of-the-art classifiers), area of 27,570 μm2 per binary classifier, and a stable response under PVT variations. Finally, to provide ground for future work on ultra-low-power deep and convolutional networks, scalability and robustness of the proposed multiplier is evaluated with a convolutional neural network on CIFAR-10. Similar classification accuracy with digital and SMART hardware has been observed. All the code and simulation files are available at an online public GitHub repository, https://github.com/faridken/SMART-Multiplier-for-ML.

PURPOSE Eight percent of young-adult childhood cancer survivors meet criteria for frailty, an aging phenotype associated with poor health. In the elderly general population, frailty is associated with neurocognitive decline; this association has not been examined in adult survivors of childhood cancer. METHODS Childhood cancer survivors 18-45 years old (≥ 10 years from diagnosis) were clinically evaluated for prefrailty or frailty (respectively defined as ≥ 2 or ≥ 3 of: muscle wasting, muscle weakness, low energy expenditure, slow walking speed, and exhaustion [Fried criteria]) and completed neuropsychologic assessments at enrollment (January 2008-June 2013) and 5 years later. Weighted linear regression using inverse of sampling probability estimates as weights compared differences in neurocognitive decline in prefrail and frail survivors versus nonfrail survivors, adjusting for diagnosis age, sex, race, CNS–directed therapy (cranial radiation, intrathecal chemotherapy, and neurosurgery), and baseline neurocognitive performance. RESULTS Survivors were on average 30 years old and 22 years from diagnosis; 18% were prefrail and 6% frail at enrollment. Frail survivors declined an average of 0.54 standard deviation (95% CI, −0.93 to −0.15) in short-term verbal recall, whereas nonfrail survivors did not decline (β = .22; difference of βs = −.76; 95% CI, −1.19 to −0.33). Frail survivors declined more than nonfrail survivors on visual-motor processing speed (β = −.40; 95% CI, −0.67 to −0.12), cognitive flexibility (β = −.62; 95% CI, −1.02 to −0.22), and verbal fluency (β = −.23; 95% CI, −0.41 to −0.05). Prefrail and frail survivors experienced greater declines in focused attention (prefrail β = −.35; 95% CI, −0.53 to −0.17; frail β = −.48; 95% CI, −0.83 to −0.12) compared with nonfrail survivors. CONCLUSION Over approximately 5 years, prefrail and frail young-adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.

New therapies for retinitis pigmentosa (RP) have led to patients desiring more information about their disease. We assessed the readability, content, and accountability of online health information for RP and its treatments.Two internet queries were performed: one pertaining to the condition RP, and another pertaining to treatments of RP. Three analyses were performed on the top search results that met eligibility criteria: (1) A readability analysis produced an average reading level; (2) A content analysis was conducted to score each source on the accuracy, completeness, clarity, and organization of the content; and (3) An accountability analysis was performed to evaluate adherence to accountability benchmarks, including authorship, attribution, disclosure, and currency.The mean reading level was 12.0 (SD = 3.2, 95% CI = 11.0-13.0) for the 8 RP webpages and 12.5 (SD = 3.1, 95% CI = 11.7-13.4) for the 10 RP treatment webpages. The mean content score for RP sites was 21.3 of 32 points (SD = 4.1, 95% CI = 19.5-23.0). The mean content score for RP treatment sites was 5.5 out of 16 points (SD = 3.7, 95% CI = 4.1-6.9). The inter-rater reliability was 0.973 (Cronbach's alpha). For RP sites, the mean accountability score was 2.6 out of 4 points (SD = 0.9, 95% CI = 1.9-3.4). For RP treatment sites, the mean accountability score was 2 out of 4 points (SD = 0.9, 95% CI = 1.4-2.6).Our data suggest that the online information available to patients regarding RP and RP treatment options exceeds the AMA-recommended sixth-grade reading level and contains gaps in content relevant to patients.

Background The ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision. Methods Pooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology. Results The combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values Conclusions EPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.