Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

The effect of clinical decision making for initiation of systemic anticancer treatments in response to the COVID-19 pandemic in England: a retrospective analysis.

BACKGROUND: Cancer services worldwide had to adapt in response to the COVID-19 pandemic to minimise risk to patients and staff. We aimed to assess the national impact of COVID-19 on the prescribing of systemic anticancer treatment in England, immediately after lockdown and after the introduction of new treatments to reduce patient risk. METHODS: We did a retrospective analysis using data from a central National Health Service England web database mandated for clinicians to register intention to start all new systemic anticancer treatments approved for use in England since 2016. We analysed the monthly number of treatment registrations in April, 2020, after the implementation of societal lockdown on March 23, 2020, and after implementation of treatment options to reduce patient risk such as oral or less immunosuppressive drugs, in May and June, 2020. We compared the number of registrations in April-June, 2020, with the mean number of registrations and SD during the previous 6 months of unaffected cancer care (September, 2019, to February, 2020). We calculated the percentage change and absolute difference in SD units for the number of registrations overall, by tumour type, and by type and line of therapy. FINDINGS: In April, 2020, 2969 registrations were recorded, representing 1417 fewer registrations than in the control period (monthly mean 4386; 32% reduction, absolute difference 4·2 SDs, p<0·0001). In May, 2020, total registrations increased to 3950, representing a 10% reduction compared with the control period (absolute difference 1·3 SDs, p<0·0001). In June, 2020, 5022 registrations were recorded, representing a 15% increase compared with the control period (absolute difference 1·9 SDs; p<0·0001]). INTERPRETATION: After the onset of the COVID-19 pandemic, there was a reduction in systemic anticancer treatment initiation in England. However, following introduction of treatment options to reduce patient risk, registrations began to increase in May, 2020, and reached higher numbers than the pre-pandemic mean in June, 2020, when other clinical and societal risk mitigation factors (such as telephone consultations, facemasks and physical distancing) are likely to have contributed. However, outcomes of providing less treatment or delaying treatment initiation, particularly for advanced cancers and neoadjuvant therapies, require continued assessment. FUNDING: None.

Treatment of gestational trophoblastic disease in the 2020s.

PURPOSE OF REVIEW: This review demonstrates the evidence for new systemic anticancer treatments and how they integrate within conventional management for gestational trophoblastic neoplasia (GTN). We present the evidence on atypical placental site nodules, and how they incorporate within the GTN spectrum, as well as updates regarding GTN staging and follow-up. RECENT FINDINGS: First-line treatment for GTN still lies in conventional chemotherapy, although the introduction of anti-PD1/PD-L1 immune checkpoint inhibitors has shown significant promise in management of relapsed disease, with responses reported in multiple relapsed choriocarcinomas as well as epithelioid trophoblastic tumours and placental site trophoblastic tumours (ETT/PSTT). Following completion of treatment, ETT/PSTT still require life-long surveillance but for other GTN, no recurrences have been detected after 7 years. SUMMARY: Checkpoint inhibitors are likely to play an increasing role in the future management of GTN management. Further refinement of prognostic factors to identify those most at risk of GTN recurrence is warranted so that surveillance can be focussed on those most at risk, whilst minimizing unnecessary intervention for those at lower risk.

Developmental impairments in moral competence as mitigation in capital cases.

In this article we propose a mitigation approach in those capital murder cases where traditional mitigation themes such as mental illness or low IQ are not present. To avoid prosecution characterization of these defendants as simply evil or antisocial personalities, we suggest reframing the issue as one of moral incompetence, based not on character defect but rather stemming from profoundly neglectful or abusive parenting. Under this reframing, defense teams would present evidence about the many antecedents of poor moral competence, its origins in neglect or abuse, its neurophysiological basis, and, most importantly, its potential for change. Evaluation in such cases would pay close attention to early childhood and family characteristics. We also recommend presentation of research findings showing how moral competence can be improved in adulthood, given appropriate guidance and support. This approach to mitigation is consistent with much of the developmental literature. But juror responses to these mitigation themes are as yet unknown.

Health Behavior Decision-making in African-American Adults Diagnosed with Schizophrenia.

Little is known about the factors that influence health behavior decision-making among people with schizophrenia. The purpose of this qualitative study was to describe the processes used by 10 African-American adults with schizophrenia when making health behavior decisions and identification of perceived barriers and facilitators to health. Three phases of health behavior decision-making were identified: Recognizing Complex Components of Health, Personalizing Components of Health, and Tracking Health Status. Findings may guide clinicians' efforts to improve the health status of patients, as well as influence future research in understanding health behavior decision-making among vulnerable populations.

A computational model for task inference in visual search.

We develop a probabilistic framework to infer the ongoing task in visual search by revealing what the subject is looking for during a search process. Based on the level of difficulty, two types of tasks, easy and difficult, are investigated in this work, and individual models are customized for them according to their specific dynamics. We use Hidden Markov Models (HMMs) to serve as a model for the human cognitive process that is responsible for directing the center of gaze (COG) according to the task at hand during visual search and generating task-dependent eye trajectories. This generative model, then, is used to estimate the likelihood term in a Bayesian inference formulation to infer the task given the eye trajectory. In the easy task, focus of attention (FOA) often lands on targets, whereas in the difficult one, in addition to the on-target foci of attention, deployment of attention on nontarget objects happens very often. Therefore, we suggest a single-state and a multi-state HMM to serve as the cognitive process model of attention for the easy and difficult tasks, respectively.

Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes.

Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumor evolution, clinical outcomes, and surgical operability. We perform systematic multi-site tumor mapping at presentation and matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing tumor clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler sympodial evolution. Three distinct tumor evolutionary patterns from primary to relapse are identified, demonstrating recurrent disease may emerge from pre-existing or newly detected clones. Crucially, we identify spatial heterogeneity for clinically actionable homologous recombination deficiency scores and for poor prognosis biomarkers CCNE1 and MYC. Copy-number signature, phenotypic, proteomic, and proliferative-index heterogeneity further highlight HGSOC complexity. This study explores HGSOC evolution and dissemination across space and time, its impact on optimal surgical cytoreductive effort and clinical outcomes, and its consequences for clinical decision-making.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

A brief personal meditation about failure and defeat.

Failure and defeat create despair, but can also create new ways to imagine our therapeutic work with people. This essay explores one approach to understanding this idea.

Implementation issues in an innovative rural substance misuser treatment program.

This article is essentially the story of the development, implementation, and testing of a treatment protocol designed specifically for rural individuals who are substance misusers. Although the treatment protocol that emerged from this process seemed to be valuable for clients, the researchers were not able to establish with statistical significance that it was better than conventional treatment. In some ways, this was a failure. This article explores some of the possible reasons why new treatment approaches, tested in real clinical situations, may have difficulty establishing their effectiveness. The factors involved are many and complex.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Spectral color constancy using a maximum entropy approach.

This paper proposes a solution to the spectral color constancy problem. The method is based on a statistical model for the surface reflectance spectrum and applies a maximum entropy constraint. Unlike prior methods based on linear models, the solution process does not require a set of basis functions to be defined, nor does it require a database of spectra to be specified in advance. Experiments on simulated and real data show that spectral estimation using the maximum entropy approach is feasible and performs similarly to existing spectral methods in spite of the lower level of a priori information required.

Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma.

Introduction: Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin-dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered: This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen.

Evaluation of a novel communication and consultation skills model (WISE COACH) on dog owner perceptions of veterinarians and projected spending on veterinary care.

OBJECTIVE: To assess the impact of a novel communication and consultation skills model (WISE COACH [WC]) on dog owner perceptions of veterinarians and projected spending on veterinary care. SAMPLE: 1,200 US dog owners who had visited a veterinarian within the prior 18 months. PROCEDURES: Video recordings of 2 staged client consultations were made, with the veterinarian following the WC recommendations in one video and not following them in the other (control). Participants were randomly assigned to view one of the videos and completed an online survey to assess their perceptions and projected spending. Qualitative responses were coded to identify themes. RESULTS: The veterinarian was rated significantly higher in the WC video than in the control video for the characteristics first impression, skilled and knowledgeable, cares about me, cares about my pet, and communicates clearly, and was rated significantly lower for the characteristic rushed or abrupt. Participants who viewed the WC video were significantly more likely to follow the veterinarian's recommendations, return to see the veterinarian, and recommend the veterinarian. They were also approximately 1.4 times as likely to approve the full recommended treatment plan, and their projected total spending was approximately 15% higher than projected spending for participants who viewed the control video. CLINICAL RELEVANCE: Results showed improved client perceptions, client retention, quality of patient care, and financial metrics when the veterinarian followed the WC recommendations. Further study is needed to determine whether this model may also improve veterinarian well-being by improving client relationships and decreasing resistance to recommendations.

Towards a Machine Vision-Based Yield Monitor for the Counting and Quality Mapping of Shallots.

In comparison to field crops such as cereals, cotton, hay and grain, specialty crops often require more resources, are usually more sensitive to sudden changes in growth conditions and are known to produce higher value products. Providing quality and quantity assessment of specialty crops during harvesting is crucial for securing higher returns and improving management practices. Technical advancements in computer and machine vision have improved the detection, quality assessment and yield estimation processes for various fruit crops, but similar methods capable of exporting a detailed yield map for vegetable crops have yet to be fully developed. A machine vision-based yield monitor was designed to perform size categorization and continuous counting of shallots in-situ during the harvesting process. Coupled with a software developed in Python, the system is composed of a video logger and a global navigation satellite system. Computer vision analysis is performed within the tractor while an RGB camera collects real-time video data of the crops under natural sunlight conditions. Vegetables are first segmented using Watershed segmentation, detected on the conveyor, and then classified by size. The system detected shallots in a subsample of the dataset with a precision of 76%. The software was also evaluated on its ability to classify the shallots into three size categories. The best performance was achieved in the large class (73%), followed by the small class (59%) and medium class (44%). Based on these results, the occasional occlusion of vegetables and inconsistent lighting conditions were the main factors that hindered performance. Although further enhancements are envisioned for the prototype system, its modular and novel design permits the mapping of a selection of other horticultural crops. Moreover, it has the potential to benefit many producers of small vegetable crops by providing them with useful harvest information in real-time.

A spectral theory of color perception.

The paper adopts the philosophical stance that colors are real and can be identified with spectral models based on the photoreceptor signals. A statistical setting represents spectral profiles as probability density functions. This permits the use of analytic tools from the field of information geometry to determine a new kind of color space and structure deriving therefrom. In particular, the metric of the color space is shown to be the Fisher information matrix. A maximum entropy technique for spectral modeling is proposed that takes into account measurement noise. Theoretical predictions provided by our approach are compared with empirical colorfulness and color similarity data.

Contemporary psychotherapy research: implications for substance misuse treatment and research.

This article provides an overview of the major findings of psychotherapy research and discusses the possible implications of these findings for substance user treatment researchers and practitioners. While the centrality of relationship for human change processes was historically understood, twentieth century research tended to see relationship and person variables as secondary to operationalized "mechanisms of action" unique to particular psychotherapies. Interestingly, recent meta-analytic investigations have uncovered the weakness of randomized controlled trials (RCT) comparison investigations that have, until recently, represented the "gold standard" for the field. There has been a resurgent interest in the "common factors" that appear to be important across many effective psychotherapies. In addition, psychiatric anthropologists have contributed important information about the problems of client noncompliance with mental health treatment that parallel quantitative investigations. Substance misuse researchers have also found that client characteristics, especially clients' readiness to engage treatment, are important to investigate. The importance of the "therapeutic alliance" and the characteristics of clients and clinicians have become central areas for study, rather than variables to be controlled or excluded. Emphasis on these factors may represent the future for research in psychotherapy and substance user treatment, especially if researchers and community practitioners can join together to overcome methodological feasibility and dissemination problems that plague effectiveness research. However, the continued attractiveness of comparative studies and treatment efficacy studies may represent longstanding epistemological assumptions and responses to economic incentives that will be difficult to challenge.

Relationship between caregiver hopefulness and satisfaction with their children's mental health services.

Relationships among the Youth Services Survey for Families (YSSF) Indicators, selected demographic and clinical variables, and caregiver-rated hopefulness and children's problem severity were examined in a random sample of 1,500 caregivers of Medicaid-enrolled youth in a satisfaction study with Kentucky's 14 community mental health centers. Multiple linear regressions revealed that caregiver services and caregiver hopefulness were excellent predictors of two and three YSSF Indicators, respectively. Providers need to respond to caregiver concerns when developing support services and understand the mechanisms associated with these services' effectiveness. Tracking changes in caregiver and youth hopefulness during treatment may improve services and retention and bridge the gap between research and the important construct of hope.

Convergent flash localization near saccades without equivalent "compression" of perceived separation.

Visual space is sometimes said to be "compressed" before saccadic eye movements. The most central evidence for this hypothesis is a converging pattern of localization errors on single flashes presented close to saccade time under certain conditions. An intuitive version of the compression hypothesis predicts that the reported distance between simultaneous, spatially separated presaccadic flashes should contract in the same way as their individual locations. In our experiment we tested this prediction by having subjects perform one of two tasks on stimuli made up of two bars simultaneously flashed near saccade time: either localizing one of the bars or judging the separation between the two. Localization judgments showed the previously observed converging pattern over the 50-100 ms before saccades. Contractions in perceived separation between the two bars were not accurately predicted by this pattern: they occurred mainly during saccades and were much weaker than convergence in localization. Different forms of spatial information about flashed stimuli can be differentially modulated before, during, and after saccades. Structural alterations in the perceptual field around saccades may explain these different effects, but alternative hypotheses based on decision making under uncertainty and on the influence of other perisaccadic mechanisms are also consistent with this and other evidence.

Infant mental health, child maltreatment, and the law: A jurisprudent therapy analysis.

Scholarly and clinical discussions of the legal issues facing infant mental health professionals typically focus on the seemingly intractable differences in philosophies, goals, and approaches inherent in the law and the mental health professions. We argue that forensically informed approaches to practice with very young children can potentially enhance many mental health and child welfare outcomes. This article describes the relatively new conceptual frameworks known as "therapeutic jurisprudence" and "jurisprudent therapy." Using these conceptual frameworks, we analyze representative problems that are typical in infant mental health practice with maltreated children through case examples drawn from their evaluations of children and families in the child protection and legal systems. Demonstrations of how such dilemmas can be approached with enhanced analytic decision-making and practice approaches are presented. We argue that applying such jurisprudent therapy approaches opens up fresh perspectives for evidence-based practices that facilitate creative, rigorous, and intellectually stimulating clinical work.