Investigating the impact of the COVID-19 pandemic on recovery colleges: multi-site qualitative study.

BACKGROUND: During the COVID-19 pandemic, mental health problems increased as access to mental health services reduced. Recovery colleges are recovery-focused adult education initiatives delivered by people with professional and lived mental health expertise. Designed to be collaborative and inclusive, they were uniquely positioned to support people experiencing mental health problems during the pandemic. There is limited research exploring the lasting impacts of the pandemic on recovery college operation and delivery to students. AIMS: To ascertain how the COVID-19 pandemic changed recovery college operation in England. METHOD: We coproduced a qualitative interview study of recovery college managers across the UK. Academics and co-researchers with lived mental health experience collaborated on conducting interviews and analysing data, using a collaborative thematic framework analysis. RESULTS: Thirty-one managers participated. Five themes were identified: complex organisational relationships, changed ways of working, navigating the rapid transition to digital delivery, responding to isolation and changes to accessibility. Two key pandemic-related changes to recovery college operation were highlighted: their use as accessible services that relieve pressure on mental health services through hybrid face-to-face and digital course delivery, and the development of digitally delivered courses for individuals with mental health needs. CONCLUSIONS: The pandemic either led to or accelerated developments in recovery college operation, leading to a positioning of recovery colleges as a preventative service with wider accessibility to people with mental health problems, people under the care of forensic mental health services and mental healthcare staff. These benefits are strengthened by relationships with partner organisations and autonomy from statutory healthcare infrastructures.

Orthopaedic Research Consortiums: A Review of Scope, Sex and Racial Representation.

Introduction The creation of research groups and consortiums has become more common in all medical and surgical specialities. The purpose of this investigation was to assess and describe collaborative research groups and consortiums within orthopaedic surgery. In addition, we aimed to define the demographics of the research consortium members with particular attention to female and minority members. Methods  Journals with a musculoskeletal/orthopaedic focus and a few medical journals were selected to identify articles published by research groups and consortiums. Articles published from 2020 to 2022 were manually reviewed. Bibliographic information, author information and level of evidence (LOE) were recorded. For identified consortium members, sex and race were defined in a binary manner. Results A total of 92 research consortiums were identified. A list of members was identified for 77 groups (83.7%), totalling 2,260 researchers. The remaining group members were not able to be identified due to the lack of information in the included publications, research group websites or after communicating with the corresponding author for respective articles. Most researchers were male (n=1,748, 77.3%) and white (n=1,694, 75%). Orthopaedic surgeons comprised 1,613 (71.4%) identified researchers. The most common fellowship training for orthopaedic surgeons was paediatrics (n=370, 16.4%), trauma (n=266, 11.8%) and sports medicine (n=229, 10.1%). The consortiums published 261 articles: women were lead (first) authors in 23% and senior (last) authors in 11.1%. Non-white researchers were lead authors in 24.5% (n=64) and senior authors in 17.2% (n=45). The most common level of evidence was level 3, accounting for 45.6% (n=119) of all publications. Level 1 evidence accounted for 12.6% (n=33) of published articles. Discussion Representation of women in orthopaedic research consortiums exceeds their representation in almost every orthopaedic professional society. There is less publicly available data to compare the involvement of under-represented minorities (URMs) in research consortiums to general practice. Further investigations should analyse possible avenues in which gender and racial disparity could be improved within orthopaedic surgery research.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

Fates of Terrigenous Dissolved Organic Carbon in the Gulf of Maine.

A significant amount of organic carbon is transported in dissolved form from soils to coastal oceans via inland water systems, bridging land and ocean carbon reservoirs. However, it has been discovered that the presence of terrigenous dissolved organic carbon (tDOC) in oceans is relatively limited. Therefore, understanding the fates of tDOC in coastal oceans is essential to account for carbon sequestration through land ecosystems and ensure accurate regional carbon budgeting. In this study, we developed a state-of-the-art modeling approach by coupling a land-to-ocean tDOC flux simulation model and a coastal tDOC tracking model to determine the potential fates of tDOC exported from three primary drainage basins in the Gulf of Maine (GoM). According to our findings, over half a year in the GoM, 56.4% of tDOC was mineralized. Biomineralization was responsible for 90% of that amount, with the remainder attributed to photomineralization. Additionally, 37% of the tDOC remained suspended in the GoM, and 6.6% was buried in the marine sediment.

Breast Cancer Circulating Tumor Cells: Current Clinical Applications and Future Prospects.

BACKGROUND: Identification and characterization of circulating tumor markers, designated as "liquid biopsies," have greatly impacted the care of cancer patients. Although more recently referring to circulating tumor DNA (ctDNA), the term liquid biopsy initially was coined to refer to any blood-borne biomarker related to malignancy, including circulating tumor cells (CTCs) in blood. In this manuscript, we review the specific state of the art of CTCs in breast cancer. CONTENT: Liquid biopsies might play a clinical role across the entire spectrum of breast cancer, from risk assessment, prevention, screening, and treatment. CTC counts have been shown to carry clear, independent prognostic information in the latter situation. However, the clinical utility of CTCs in breast cancer remains to be determined. Nonetheless, in addition to CTC enumeration, analyses of CTCs provide tumor molecular information representing the entire, often-heterogeneous disease, relatively noninvasively and longitudinally. Technological advances have allowed the interrogation of CTC-derived information, providing renewed hope for a clinical role in disease monitoring and precision oncology. SUMMARY: This narrative review examines CTCs, their clinical validity, and current prospects of clinical utility in breast cancer with the goal of improving patient outcomes.

Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer.

PURPOSE: Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. METHODS: This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. RESULTS: In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. CONCLUSION: Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Near-Infrared Induced miR-34a Delivery from Nanoparticles in Esophageal Cancer Treatment.

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics. The light-inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near-infrared (NIR) region of the light spectrum. Through this method, exogenous miR-34a-5p mimics are effectively delivered to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system is tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments reveal that this CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, 6 h post-injection, produce a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 h.

A Comparison of Early Complication Rates of Endoscopic Carpal Tunnel Release With and Without Resident Involvement.

PURPOSE: The purpose of this study was to compare the complication rates of endoscopic carpal tunnel release (ECTR) relative to orthopedic resident trainee involvement in the procedure. METHODS: All patients undergoing isolated, elective ECTR by two attending surgeons within a 59-month period were analyzed. Cases were categorized as the following according to the degree of resident involvement: ECTR performed by attending with either no resident or a resident as an assistant (group 1), resident performing a portion of the procedure (group 2), and resident performing the entire procedure (group 3). Early postoperative complications and/or intraoperative conversion to an open procedure were the outcomes of interest. We used a noninferiority design, hypothesizing that resident involvement would not be associated with inferior outcomes compared with cases without resident involvement. Multiple logistic regression models, adjusted for patient demographic and surgical characteristics, were fit to assess the relationship between resident involvement groups and complication/conversion outcomes. RESULTS: A total of 1,167 ECTR cases (895 patients) were performed and returned for postoperative follow-up for at least 2 weeks after surgery. Operative time was significantly shorter for group 1 cases versus group 2 and 3 cases. The early postoperative complication and conversion rates were 1.7% and 1.0%, respectively. Superficial infection (1.2%), deep infection (0.3%), and transient neuropraxia (0.3%) occurred infrequently and did not differ relative to resident involvement. No differences in the odds of complication and/or conversion relative to resident involvement were observed. CONCLUSIONS: The results of ECTR performed entirely or in part by attending-supervised resident trainees were not inferior to ECTR performed by an attending surgeon regarding the odds of experiencing complications or conversion to an open procedure. With appropriate supervision, ECTR can be performed safely by orthopedic and plastic surgery residents. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Adherence to Complication Reporting for Randomized Controlled Trials Contained in Clinical Practice Guidelines for the Management of Carpal Tunnel Syndrome.

Purpose: Randomized controlled trials (RCTs) are frequently used in creating recommendations contained within clinical practice guidelines (CPGs). However, investigations outside of hand surgery have reported that RCTs within CPGs infrequently report complications and harms-related data. Our purpose was to assess adherence to complication reporting and harms-related outcomes contained in the Consolidated Standards for Reporting (CONSORT) Extension of Harms and Standards for Reporting of Diagnostic Accuracy Studies (STARD) reporting checklists for RCTs within the American Academy of Orthopaedic Surgery (AAOS) CPGs for carpal tunnel syndrome (CTS). Methods: We identified all RCTs within the AAOS CTS CPGs. All therapeutic RCTs and diagnostic studies were included. We used the CONSORT Harms Checklist criteria to assess adherence to the reporting of adverse events for therapeutic RCTs and the STARD criteria to assess the diagnostic accuracy of the articles. We defined adequate compliance as adherence to ≥50% of the checklist items. Results: We identified 82 therapeutic RCTs and 90 diagnostic accuracy articles within the AAOS CTS CPG. For therapeutic RCTs, we found that the average compliance with the published checklists was 19%. For diagnostic studies, the average compliance with checklists was found to be 55%. Eleven therapeutic RCTs (13%) and 60 diagnostic studies (67%) were determined to have adequate compliance for the CONSORT and STARD checklists, respectively. Conclusions: Randomized controlled trials in the AAOS CPGs for CTS have low compliance with the CONSORT Extension for Harms Checklist. Although the overall adherence to the items published in the STARD statement for diagnostic accuracy evaluation remains higher, future efforts should be made to improve the adherence rates to both checklists. Clinical relevance: Improved standardization of complication reporting may aid in comparing outcomes across multiple clinical investigations of upper-extremity procedures.

Defining young people's mental health self-care: a systematic review and co-development approach.

Self-care is among the emerging types of mental health support which operate outside traditional services, although the meaning and practice of self-care for young people with mental health difficulties are currently unclear. This systematic review was pre-registered with PROSPERO (CRD42021282510) and investigated conceptualizations of self-care in academic publications which investigated or discussed self-care for young people's mental health or wellbeing. A Patient and Public Involvement (PPI) workshop facilitated young people with experience of mental health difficulties to respond to the identified concepts and co-develop a definition of self-care. Searches in PsycINFO, MEDLINE, Embase, CINAHL Plus, Scopus, Cochrane Library of Systematic Reviews, and gray literature sources resulted in 90 included publications. Content analysis indicated little conceptual consistency, with health and wellness promotion most commonly used to define self-care. The PPI workshop co-developed a definition of mental health self-care, which attendees felt should emphasize an individual process of self-awareness, self-compassion, and specific strategies to work toward emotional balance. This study highlights the gap between current academic understandings of young people's mental health self-care and young people's experience. The presented definition will enable future research to begin from an understanding of self-care which is relevant to young people with experience of mental health difficulties.

Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency.

PURPOSE: Triple-negative breast cancer (TNBC) is a heterogeneous disease. We previously showed that homologous recombination deficiency (HRD) and the DNA damage immune response (DDIR) signature are prognostic in TNBC. We hypothesized that these biomarkers reflect related but not completely interdependent biological processes, that their combined use would be prognostic, and that simultaneous assessment of the immunologic microenvironment and susceptibility to DNA damaging therapies might be able to identify subgroups with distinct therapeutic vulnerabilities. METHODS: We analyzed the dual DDIR/HRD classification in 341 patients with TNBC treated with adjuvant anthracycline-based chemotherapy on the SWOG S9313 trial and corroborated our findings in The Cancer Genome Atlas breast cancer data set. RESULTS: DDIR/HRD classification is highly prognostic in TNBC and identifies biologically and immunologically distinct subgroups. Immune-enriched DDIR+/HRD+ TNBCs have the most favorable prognosis, and DDIR+/HRD- and DDIR-/HRD+ TNBCs have favorable intermediate prognosis, despite the latter being immune-depleted. DDIR-/HRD- TNBCs have the worst prognosis and represent an internally heterogeneous group of immune-depleted chemoresistant tumors. CONCLUSION: Our findings propose DDIR/HRD classification as a potentially clinically relevant approach to categorize tumors on the basis of therapeutic vulnerabilities.

Defining Nonunion for Metacarpal Fractures: A Systematic Review.

Purpose: Our purpose was to assess how nonunion of the metacarpals has been defined in prior investigations with respect to both clinical and radiographic criteria. We hypothesized that the definitions of nonunion would be highly variable. Methods: A systematic review was conducted using MEDLINE and Embase databases for clinical articles related to the treatment of metacarpal fractures (surgical and nonsurgical) from 2010 to 2021. Included articles were searched to assess how nonunion was defined based on clinical and radiographic criteria. We assessed the treatment type, method of union assessment, time to union, and incidence of union as well as article factors such as the following: date of publication, level of evidence, and publishing journal. Results: A total of 641 articles were identified, of which 102 were included for a definition of nonunion and 97 were included for the assessment of clinical management and outcomes. Of the included articles, 62% contained level IV evidence. A definition of nonunion was provided in 47% of the articles. Radiographic criteria alone, clinical criteria alone, or a combination of the 2 was used in 22%, 6%, and 19% of the cases, respectively, to define nonunion. The most common definition of nonunion was presence of fracture-site tenderness (with no time defined) in 20 articles (20%), followed by lack of radiographic healing at 6 months (15%). In the 97 included articles, the total number of fracture cases was 4,435 and nonunion was reported in 0.45%. Cases with nonunion were reported in a total of six articles that used a variety of treatment modalities. Conclusions: The definition of metacarpal nonunion remains highly variable and lacks standardization with respect to clinical and radiographic criteria. Clinical relevance: Standardizing the definition of nonunion for metacarpal fractures would allow for more accurate assessments of the incidence of this complication and may aid in improving diagnostic and management strategies.

Organisational and student characteristics, fidelity, funding models, and unit costs of recovery colleges in 28 countries: a cross-sectional survey.

BACKGROUND: Recovery colleges were developed in England to support the recovery of individuals who have mental health symptoms or mental illness. They have been founded in many countries but there has been little international research on recovery colleges and no studies investigating their staffing, fidelity, or costs. We aimed to characterise recovery colleges internationally, to understand organisational and student characteristics, fidelity, and budget. METHODS: In this cross-sectional study, we identified all countries in which recovery colleges exist. We repeated a cross-sectional survey done in England for recovery colleges in 28 countries. In both surveys, recovery colleges were defined as services that supported personal recovery, that were coproduced with students and staff, and where students learned collaboratively with trainers. Recovery college managers completed the survey. The survey included questions about organisational and student characteristics, fidelity to the RECOLLECT Fidelity Measure, funding models, and unit costs. Recovery colleges were grouped by country and continent and presented descriptively. We used regression models to explore continental differences in fidelity, using England as the reference group. FINDINGS: We identified 221 recovery colleges operating across 28 countries, in five continents. Overall, 174 (79%) of 221 recovery colleges participated. Most recovery colleges scored highly on fidelity. Overall scores for fidelity (ß=-2·88, 95% CI 4·44 to -1·32; p=0·0001), coproduction (odds ratio [OR] 0·10, 95% CI 0·03 to 0·33; p<0·0001), and being tailored to the student (OR 0·10, 0·02 to 0·39; p=0·0010), were lower for recovery colleges in Asia than in England. No other significant differences were identified between recovery colleges in England, and those in other continents where recovery colleges were present. 133 recovery colleges provided data on annual budgets, which ranged from €0 to €2 550 000, varying extensively within and between continents. From included data, all annual budgets reported by the college added up to €30 million, providing 19 864 courses for 55 161 students. INTERPRETATION: Recovery colleges exist in many countries. There is an international consensus on key operating principles, especially equality and a commitment to recovery, and most recovery colleges achieve moderate to high fidelity to the original model, irrespective of the income band of their country. Cultural differences need to be considered in assessing coproduction and approaches to individualising support. FUNDING: National Institute for Health and Care Research.

Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226.

Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (ß-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.

Sensitivity and Specificity of Examination Maneuvers for Carpal Tunnel Syndrome: A Meta-Analysis.

Our purpose was to assess the diagnostic validity (sensitivity (Sn) and specificity (Sp)) of physical examination maneuvers for carpal tunnel syndrome (CTS). This meta-analysis utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Studies assessing exam maneuvers (including components of the CTS-6) for CTS were identified in MEDLINE (Medical Literature Analysis and Retrieval System Online) and Embase (Excerpta Medica Database) databases. Assessed maneuvers assessed included: Phalen's test, Tinel's sign, Durkan test, scratch-collapse test, Semmes-Weinstein monofilament (SWM), and static 2-point discrimination (2PD) test. Data extracted included: article name, total number of subjects/hands, type of exam, and exam Sn/Sp. Forest plots were presented to display the estimated Sn/Sp and boxplots were used to demonstrate the locality, spread, and skewness of the Sn/Sp through the quartiles. After screening 570 articles, 67 articles involving 8924 hands were included. Forty-eight articles assessed Phalen's test, 45 assessed Tinel's sign, 21 assessed the Durkan test, seven assessed the scratch-collapse test, 11 assessed SWM, and six assessed the static 2PD test. Phalen's test demonstrated the greatest median Sn (0.70, (Q1, Q3): (0.51, 0.85)), followed by the Durkan test (0.67, (Q1, Q3): (0.46, 0.82)). 2PD demonstrated the highest median Sp (0.90, (Q1, Q3): (0.88, 0.90)), followed by SWM (0.85, (Q1, Q3): (0.51, 0.89)). There is considerable variability with respect to the validity of physical exam tests used in the diagnosis of CTS. Upper-extremity surgeons should be aware of inherent limitations for individual exam maneuvers. In the absence of a uniformly accepted diagnostic gold standard, a combination of exams, along with pertinent patient history, should guide the diagnosis of CTS.

Photodynamic Therapy for Glioblastoma: Illuminating the Path toward Clinical Applicability.

Glioblastoma (GBM) is the most common adult brain cancer. Despite extensive treatment protocols comprised of maximal surgical resection and adjuvant chemo-radiation, all glioblastomas recur and are eventually fatal. Emerging as a novel investigation for GBM treatment, photodynamic therapy (PDT) is a light-based modality that offers spatially and temporally specific delivery of anti-cancer therapy with limited systemic toxicity, making it an attractive option to target GBM cells remaining beyond the margins of surgical resection. Prior PDT approaches in GBM have been predominantly based on 5-aminolevulinic acid (5-ALA), a systemically administered drug that is metabolized only in cancer cells, prompting the release of reactive oxygen species (ROS), inducing tumor cell death via apoptosis. Hence, this review sets out to provide an overview of current PDT strategies, specifically addressing both the potential and shortcomings of 5-ALA as the most implemented photosensitizer. Subsequently, the challenges that impede the clinical translation of PDT are thoroughly analyzed, considering relevant gaps in the current PDT literature, such as variable uptake of 5-ALA by tumor cells, insufficient tissue penetrance of visible light, and poor oxygen recovery in 5-ALA-based PDT. Finally, novel investigations with the potential to improve the clinical applicability of PDT are highlighted, including longitudinal PDT delivery, photoimmunotherapy, nanoparticle-linked photosensitizers, and near-infrared radiation. The review concludes with commentary on clinical trials currently furthering the field of PDT for GBM. Ultimately, through addressing barriers to clinical translation of PDT and proposing solutions, this review provides a path for optimizing PDT as a paradigm-shifting treatment for GBM.

Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation.

This study describes the development of an ultrasound-responsive polymer system that provides on-demand degradation when exposed to high-intensity focused ultrasound (HIFU). Diels-Alder cycloadducts were used to crosslink polycaprolactone (PCL) polymers and underwent a retro Diels-Alder reaction when stimulated with HIFU. Two Diels-Alder polymer compositions were explored to evaluate the link between reverse reaction energy barriers and polymer degradation rates. PCL crosslinked with isosorbide was also used as a non-Diels-Alder-based control polymer. An increase of HIFU exposure time and amplitude correlated with an increase of PCL degradation for Diels-Alder-based polymers. Ultrasound imaging during HIFU allowed for real-time visualization of the on-demand degradation through cavitation-based mechanisms. The temperature surrounding the sample was monitored with a thermocouple during HIFU stimulation; a minimal increase in temperature was observed. PCL polymers were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), optical profilometry, and mechanical testing. PCL degradation byproducts were identified by mass spectrometry, and their cytocompatibility was evaluated in vitro. Overall, this study demonstrated that HIFU is an effective image-guided, external stimulus to control the degradation of Diels-Alder-based PCL polymers on-demand.

A Foundational Population Genetics Investigation of the Sexual Systems of Solanum (Solanaceae) in the Australian Monsoon Tropics Suggests Dioecious Taxa May Benefit from Increased Genetic Admixture via Obligate Outcrossing.

Solanum section Leptostemonum is an ideal lineage to test the theoretical framework regarding proposed evolutionary benefits of outcrossing sexual systems in comparison to cosexuality. Theoretically, non-cosexual taxa should support more genetic diversity within populations, experience less inbreeding, and have less genetic structure due to a restricted ability to self-fertilize. However, many confounding factors present challenges for a confident inference that inherent differences in sexual systems influence observed genetic patterns among populations. This study provides a foundational baseline of the population genetics of several species of different sexual systems with the aim of generating hypotheses of any factor-including sexual system-that influences genetic patterns. Importantly, results indicate that dioecious S. asymmetriphyllum maintains less genetic structure and greater admixture among populations than cosexual S. raphiotes at the same three locations where they co-occur. This suggests that when certain conditions are met, the evolution of dioecy may have proceeded as a means to avoid genetic consequences of self-compatibility and may support hypotheses of benefits gained through differential resource allocation partitioned across sexes. Arguably, the most significant finding of this study is that all taxa are strongly inbred, possibly reflective of a shared response to recent climate shifts, such as the increased frequency and intensity of the region's fire regime.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update.

PURPOSE: To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. METHODS: An Update Panel conducted a systematic literature review to identify signals for updating recommendations. RESULTS: The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations. RECOMMENDATIONS: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. DISCUSSION: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.Additional information is available at www.asco.org/breast-cancer-guidelines.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer.

PURPOSE.­: To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. METHODS.­: The Update Panel conducted a systematic literature review to identify signals for updating recommendations. RESULTS.­: The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations. RECOMMENDATIONS.­: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. DISCUSSION.­: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.