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Introduction Inadequate treatment of enlarged lateral lymph nodes (LLNs) in rectal cancer patients is associated with an increased lateral local recurrence (LLR) risk, despite neoadjuvant treatment and total mesorectal excision (TME) surgery. There is a promising role for LLN dissection (LLND) to lower this risk, but this challenging procedure requires appropriate training. This study protocol describes a prospective evaluation of oncological outcomes after standardised treatment based on multidisciplinary training, thereby aiming for a 50% reduction in LLR rate.Methods and analysis A prospective registration study will be opened in hospitals in which the involved multidisciplinary team members (radiologists, radiation oncologists, surgeons and pathologists) have received dedicated training to enhance knowledge and awareness of LLNs and in which standardised treatment including LLND has been implemented. Patients with rectal cancer and at least one enlarged LLN (short-axis ≥7.0 mm), or intermediate LLN (short-axis 5.0–6.9 mm) with at least one malignant feature on primary MRI, evaluated by a trained radiologist, are eligible. Patients will undergo neoadjuvant treatment by trained radiation oncologists, followed by TME surgery in combination with a minimally invasive, nerve-sparing LLND performed by trained surgeons. LLND specimens are evaluated by trained pathologists or grossing assistants. The primary outcome is LLR rate 3 years postoperatively. Secondary outcomes are morbidity, disease-free survival, overall survival and quality of life. To demonstrate a significant reduction in LLR rate from 13% (based on historical control data) to 6% after optimised treatment, 200 patients with enlarged LLNs are required.Ethics and dissemination The medical ethics board of the Vrije Universiteit Medical Centre (VUMC), the Netherlands, approved the study on 23 November 2022 (reference: 2021.0524). Participating centres must obtain local approval and participants are required to provide written informed consent. Results obtained from this study will be communicated via peer-reviewed medical journals and presentations at conferences.Trail registration number NCT04486131, 24 July 2020, https://clinicaltrials.gov/ct2/show/NCT04486131.

The guilty verdict handed down to Officer Derek Chauvin for the George Floyd murder draped a sad pause over America's raging torrent of gun violence. Throughout our history, police killings […]

Objective: To determine whether chronic pain persists after complete spinal cord injury (SCI). Design: Prospective observational study regarding the outcome of pre-existent chronic pain of inpatients admitted with new clinically diagnosed complete cervical SCI. For patients who acknowledged chronic pain of ≥3 years duration before the SCI, further questions explored whether they still experienced that pain, whether they were experiencing current posttraumatic pain, and whether they had any past exposure to opioids. The included patients were identified during the initial consultation in the trauma center for treatment of the SCI. Setting: Level I trauma center. Participants: From a total of 49 participants with acute cervical SCI with clinically diagnosed complete motor and sensory tetraplegia admitted between 2018 and 2020, 7 were selected on the basis of a history of chronic pain. Intervention: Collected complete history and performed physical examination with serial follow-ups during the acute hospital stay until death or discharge. Main Outcome Measures: The primary outcome was a finding of chronic pain experienced before new clinical diagnosis of complete SCI, compared with whether or not that pain continued after the SCI injury. The secondary outcome was the relation of persistent pain with opioid use; it was formulated after data collection. Results: Among 49 patients with clinically diagnosed complete cervical SCIs, 7 had experienced prior chronic pain. Four participants experienced a continuation of the prior pain after their complete tetraplegia (4/7), whereas 3 participants did not (3/7). All the participants with continued pain had been previously treated with opioids, whereas those whose pain ceased had not received chronic opioid therapy. Conclusions: There may be a unique form of chronic pain that is based in the brain, irrespective of peripheral pain or spinal mechanisms. Otherwise healthy people with longstanding antecedent chronic pain whose pain persists after acute clinically complete SCI with tetraplegia may provide a new model for evaluation of brain-based pain. Opioids may be requisite for this type of pain.

The voice of Jolson is deep, resonant. Its Its swirling waves flood the basement. The concrete walls and wooden ceiling surrounding the phonograph echo the deep, sumptuous tones. Then Jolson's […]

Abstract Background With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID‐19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID‐19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll‐out and to identify risk factors associated with hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality. Methods We performed a retrospective cohort study of cancer patients with COVID‐19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. Results Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID‐19, severe COVID‐19, and 30‐day COVID‐19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID‐19 but with no impact on hospitalization or mortality due to COVID‐19. Conclusion Our study highlights a significant benefit of COVID‐19 vaccination for cancer patients—specifically its protection against severe COVID‐19.

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients’ response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3–6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3–6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3–6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3–6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed.

Background: The purpose of this study was to assess the protective influence of individual, family, and community assets from the initiation of sexual intercourse (ISI) for adolescents living in one-parent households compared with adolescents living in two-parent households. Methods: Five waves of data were collected annually over a 4-year period (N = 591, 52.5% female, mean age = 14.0 years) from a racially/ethnically diverse sample of adolescents. Extended Cox models were used to assess the relationship between assets and time of ISI while controlling for demographic variables. Potential interactions between adolescent's household structure and assets were examined. Results: Five of 17 assets were prospectively and significantly associated with a reduced risk of ISI among adolescents living in one-parent households compared with 11 of 17 assets for adolescents living in two-parent households. Adolescents living in one-parent households who possessed any one of five assets (e.g., general aspirations for the future, relationship with mother, positive peer role models) had between a 27% and 57% lower risk of ISI, whereas adolescents living in two-parent households who possessed any of one of 11 assets (e.g., responsible choices, family communication, community involvement) had between a 20% and 42% lower risk of ISI. Conclusion: The results suggest that strengthening specific youth assets across multiple dimensions of behavioral influence may decrease the risk of ISI for adolescents living in both one-parent and two-parent households. Public health efforts focused on developing programs to promote asset building tailored to adolescent's family structure are warranted.

The paper establishes the effective utilization of North American Electric Reliability Corporation control performance standards for cascaded fractional order controller in dispensing regulation ancillary service to the deregulated structures having intermittent generating units. The flow resources that highly contribute in faster regulatory facility include photovoltaic and wind systems. For a two area network, the control performance standard 1and balancing authority ACE limits, the successor to CPS2 are assumed to be the control inputs to the fuzzy logic base and its tuned output gain is fed to the cascaded proportional-integral-derivative double staged FOPID controller for best fallouts in dynamic stability and frequency response leveraged under diverse market contracts. Reduced depletion and depreciation in the generating unit equipment by restricted operation of the turbine valves in accordance to the generation load mismatch is the foremost virtue of the suggested performance metrics. The concurrent feed of the above mentioned standards to the fuzzy logic base against varying disturbances, contrary to thermal constraints in iterative sequence, grades to uniform reliability and consistent generation-load balance. The effectiveness of the suggested controller is verified in MATLAB forum against existing classical, cascaded and intelligent centered FO controllers manifested with artificial hummingbird algorithm owing to its proven supremacy and robustness in literature. The analytical effects in transient mode of operation is evaluated with integral time absolute error as fitness function as it epitomizes the reduction of larger errors at the initial and longer transient response state.

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients’ rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified in 2012. Eleven of twenty-eight patients with DR-VRE were never exposed to daptomycin, suggesting horizontal transmission. Fifteen of the twenty-eight patients with DR-VRE died within 30 days of positive blood cultures. Amongst those, one DR-VRE strain belonging to ST1471 had the virulence gene bopD responsible for biofilm formation. Additionally, to our knowledge, this is the first report of a DR-VRE strain belonging to ST323 in the United States. In summary, our study demonstrated the emergence and persistence of VRE strains, especially DR-VRE, in our hospital. Adding WGS to routine infection control measures may timely identify potential horizontal VRE transmission including multi-drug-resistant isolates.

Abstract Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission duration or spaceflight experience history (i.e., novice or experienced, number of prior missions, time between missions). Here we addressed this issue by quantifying regional voxelwise changes in brain gray matter volume, white matter microstructure, extracellular free water (FW) distribution, and ventricular volume from pre- to post-flight in a sample of 30 astronauts. We found that longer missions were associated with greater expansion of the right lateral and third ventricles, with the majority of expansion occurring during the first 6 months in space then appearing to taper off for longer missions. Longer inter-mission intervals were associated with greater expansion of the ventricles following flight; crew with less than 3 years of time to recover between successive flights showed little to no enlargement of the lateral and third ventricles. These findings demonstrate that ventricle expansion continues with spaceflight with increasing mission duration, and inter-mission intervals less than 3 years may not allow sufficient time for the ventricles to fully recover their compensatory capacity. These findings illustrate some potential plateaus in and boundaries of human brain changes with spaceflight.

Abstract Objectives Hematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. Methods We included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant. Results We collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p

IntroductionWe analyzed the importance of fan identity and brand strength on fans’ neural reactions to different team-related stimuli.MethodsA total of 53 fMRI scans with fans of two professional sport teams were conducted. Following up on a previous study we focused on the differences between fandom levels as well as the contrast between two team “brand” strength. Neural responses were compared among individuals based on their levels of fan identity. In sum, group comparisons between relatively high and lower identity and between weak and strong teams were made based on the notion that the latter reflects team brand strength (strong brand and weak brand).ResultsFindings indicate that brain activity in emotion regulation, memory, and cognitive control circuits is influenced by the relative level of fan identity.DiscussionHigher-level identified fans showed increased reactivity to positive stimuli and the under-recruitment of their cognitive appraisal circuits, suggesting more vulnerability to marketers’ messages. The strength of the team brand activates different neural mechanisms. Interestingly, the posterior cingulate showed larger recruitment both for weaker brands and lower fan identification, suggesting that visual memory processes are more active in these cases. Neurally processed content depends on the relative brand’s strength, highlighting the importance of brand-focused communications.

IntroductionEndometrial cancer (EC) is the most common gynecological cancer with a rising incidence, attributed to advanced life expectancy and obesity. Adipose tissue (AT) is an important endocrine organ, and its metabolic activity is affected by the different anatomical distribution or locations. AT distribution influences a number of diseases. In EC, it remains unclear whether the type of AT distribution affects development or prognosis. This systematic review aimed to determine whether AT distribution is associated with patient characteristics, disease characteristics, and patient prognosis in EC.Materials and methodsA search was conducted in Medline, MEDLINE EMBASE, and Cochrane Library. We included studies that enrolled patients with EC with any histological subtype and that distinguished between the visceral and subcutaneous AT compartment. In eligible studies, correlative analyses were performed for all outcome measures and AT distribution.ResultsEleven retrospective studies were included, with a wide range of measurements for the visceral and subcutaneous AT compartments. AT distribution was found to be significantly correlated to a number of relevant (disease) characteristics including obesity measures, histological subtype, lymph node metastasis, and sex steroid levels. Five studies reported on survival parameters including overall survival, progression-free survival and disease-specific survival, and they found that increased VAT volume was statistically significantly associated with a worse survival.Discussion/conclusionThis review demonstrates that there are significant correlations between AT distribution and prognosis, body mass index, sex steroid levels, and disease characteristics like histology. Well-designed, prospective, and larger-scale studies are needed to pinpoint these differences more specifically and understand how it can add in prediction and even therapy in EC.

Abstract Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T 1-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60–0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T 1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

This investigation elucidates what makes a good working life. A sample of 678 employees from diverse jobs rated their job satisfaction, work meaningfulness, and work psychological richness, as well as several key work characteristics (both stressors and resources) and important work and life outcomes. We explored the unique contributions of satisfaction, meaningfulness, and psychological richness by controlling each measure for the other two. Job satisfaction correlates were consistent with previous work, namely stressors and negative outcomes correlated negatively, whereas resources and positive outcomes correlated positively. More surprisingly, psychological richness was positively correlated with both stressors and resources, as well as with high rates of feeling exhausted after work and with thoughts of changing jobs. Meaningfulness, meanwhile, had relatively weak correlates after controlling for psychological richness and satisfaction. The strongest were with being proficient at the job, being highly engaged with it, and coping well with changes affecting the work role. [ABSTRACT FROM AUTHOR]

There are two ways for a situation to be uncertain. Subjective uncertainty refers to not knowing facts. Objective uncertainty refers to future events that have not been determined yet. A wide ranging literature review finds that subjective uncertainty inhibits behavior, increases conserving resources and willpower, and stimulates search for information – though in crude, sometimes dysfunctional fashion. In contrast, objective uncertainty calls for action, reflected in agentic control, increased arousal, and greater willingness to take risks. Again, some responses are irrational, such as exerting more effort for less expected reward, and betting more on uncontrollable future than past events. With both kinds of uncertainty, attention is mobilized and emotion is prolonged. Our review uncovered multiple signs that some uncertainty is beneficial and heightens enjoyment as a kind of spice of life, or, in some cases, as a welcome hope that a bad outcome might still be avoided. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work. [ABSTRACT FROM AUTHOR]

This essay strives to challenge a conceptual foundation of psychology that is questioned all too rarely: causal determinism. Specifically, the issue we have an argument with is the idea that human behavior is characterized by strict and inevitable sequences of cause and effect. We make two arguments against this notion. First, we argue that, even if true, this conception of determinism is useless and misleading for psychological theories, because psychological theories typically must explain how agents respond to situations defined by having multiple alternative possible outcomes. Second, we argue that this determinism is probably wrong, outdated, and circular in its reasoning. Alongside these arguments, we present results of a survey among fellow researchers, assessing their beliefs on the topic. Results show that psychologists are indeed discordant about this issue, and tendencies to endorse notions of causal determinism are more prevalent in younger than older scientists. We respect this diversity of opinion and seek to make the case that psychology theory would be best served by abandoning the wrongheaded idea of human behavior being inevitable and physically predetermined and replacing it with a brain-based agent operating in a world defined by multiple genuine possibilities and probabilistic causation. [ABSTRACT FROM AUTHOR]

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3–6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3–6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3–6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3–6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed. [ABSTRACT FROM AUTHOR]

Introduction High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. Methods Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." Results PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

This study's purpose was to determine whether specific youth assets (conceptualized as influencing health behavior at the individual, family, or community level) were prospectively associated with reduced alcohol, tobacco, and other drug use (ATD) in a sample of Hispanic youth. A longitudinal community-based study was conducted with five waves of data collected annually over 4 years. Participants were Hispanic youth (14.1 years old; 53% female) and their parents (N = 306 youth/parent pairs). Generalized linear mixed models were used to determine the prospective influence of 17 youth assets on ATD over five waves of data. Results indicated that Hispanic youth with three of seven individual-level assets (e.g., educational aspirations), any of four family-level assets (e.g., family communication), or with one of six community-level assets (e.g., positive peer role models) were significantly less likely to engage in ATD. The results suggest that assets protect Hispanic youth from ATD and that family-level assets may be particularly important.