Search for Sterile Neutrinos in MINOS and MINOS+ Using a Two-Detector Fit.

A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.

Severe childhood trauma and clinical and neurocognitive features in schizotypal personality disorder.

OBJECTIVE: Literature suggests that childhood trauma increases vulnerability for schizophrenia-spectrum disorders, including schizotypal personality disorder (SPD). Yet, it remains unexplored whether childhood trauma predicts symptom load and the level of neurocognitive functioning in SPD. METHOD: We included 225 individuals with SPD and 127 healthy controls. Childhood trauma was evaluated using the Childhood Trauma Questionnaire, and schizotypal traits were assessed using the Schizotypal Personality Questionnaire. Standard neurocognitive assessments covered six cognitive domains. RESULTS: All types of reported childhood trauma were significantly associated with SPD, in a linear fashion. Severe sexual abuse showed the greatest magnitude of association with higher cognitive-perceptual load (e.g., ideas of reference, odd belief or magical thinking); severe emotional neglect was associated with interpersonal scores (e.g., excessive social anxiety, constricted affect) within the SPD group. SPD individuals who reported severe trauma showed worse cognitive functioning (i.e., working memory, verbal/visual learning and memory, as well as verbal fluency). CONCLUSIONS: Particular severe childhood trauma types were associated with higher cognitive-perceptual and interpersonal symptoms in SPD, along with worse cognitive functioning. These findings highlight the need for clinicians to enquire about childhood trauma in SPD patients, since unaddressed early adverse experiences may carry long-term negative consequences.

Effects of whole blood leukoreduction on platelet function and hemostatic parameters.

AIMS/OBJECTIVES: The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). BACKGROUND: Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. METHODS: Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. RESULTS: The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. CONCLUSION: Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

Factors affecting early identification of pregnant women by community health workers in Morogoro, Tanzania.

BACKGROUND: It is recommended that Antenatal Care (ANC) be initiated within the first trimester of pregnancy for essential interventions, such folic acid supplementation, to be effective. In Tanzania, only 24% of mothers attend their first ANC appointment during their first trimester. Studies have shown that women who have had contact with a health worker are more likely to attend their first antenatal care appointment earlier in pregnancy. Community health workers (CHWs) are in an opportune position to be this contact. This study explored CHW experiences with identifying women early in gestation to refer them to facility-based antenatal care services in Morogoro, Tanzania. METHODS: This qualitative study employed 10 semi-structured focus group discussions, 5 with 34 CHWs and 5 with 34 recently delivered women in three districts in Morogoro, Tanzania. A thematic analytical approach was used to identify emerging themes among the CHW and RDW responses. RESULTS: Study findings show CHWs play a major role in identifying pregnant women in their communities and linking them with health facilities. Lack of trust and other factors, however, affect early pregnancy identification by the CHWs. They utilize several methods to identify pregnant women, including: asking direct questions to households when collecting information on the national census, conducting frequent household visits and getting information about pregnant women from health facilities. CONCLUSIONS: We present a framework for the interaction of factors that affect CHWs' ability to identify pregnant women early in gestation. Further studies need to be conducted investigating optimal workload for CHWs, as well as reasons pregnant women might conceal their pregnancies.

Selective modification of fluciclovine (18F) transport in prostate carcinoma xenografts.

We investigated if previously demonstrated inhibition of fluciclovine (18F) in vitro could be replicated in a PC3-Luc xenograft mouse model. Following intratumoral injection of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), alpha-(methylamino)isobutyric acid (MeAIB) or saline, fluciclovine PET tumor-to-background activity was 43.6 (± 5.4)% and 25.3 (± 5.2)% lower in BCH (n = 6) and MeAIB (n = 5) injected PC3 Luc xenografts, respectively, compared to saline-injected controls (n = 2). Partial inhibition of fluciclovine uptake by BCH and MeAIB can be demonstrated in vivo similar to previous in vitro modeling.

Relative social standing and suicide ideation among Kenyan males: the interpersonal theory of suicide in context.

PURPOSE: The purpose of this study is to investigate the association between subjective social status and suicide ideation in a sample of young Kenyan men (age 18-34 years). Situating insights from the interpersonal theory of suicide within social determinants of health framework, we consider whether lower subjective social status predicts lower collective self-esteem (CSE), hopelessness, less meaning in life and more loneliness, and whether these characteristics mediate associations between subjective social status and suicide ideation. METHOD: A community-based, semi-rural sample (n = 532) of young men, aged 18-34 years, was collected using a standardized questionnaire. The survey questionnaire included the following validated scale items: the short form of the Social and Emotional Loneliness Scale for Adults, CSE, Herth Hope Index, the Meaning in Life Questionnaire, and the Modified Scale for Suicide Ideation. Regression and mediation analyses were used to test hypotheses. RESULTS: Nearly 12% of respondents reported suicide ideation. Suicide ideation was significantly more common among survey respondents who reported lower subjective social standing. In the first of two mediation models, we found that lower CSE and more loneliness mediate the association between lower subjective social status and suicide ideation. In the second model, we found that respondents with lower CSE and more loneliness expressed lower hope and meaning in life, which also mediated pathways to suicide ideation. CONCLUSIONS: Findings show a novel synthesis of social determinants literature with the interpersonal theory of suicide. Suicide ideation, along with other mental and social outcomes, may figure more prominently than previously appreciated in the benefits of socio-economic equality. Those who do not participate equally in socio-economic development may be at greater risk of engaging in suicide ideation and behaviors. Suicide prevention research and programmatic responses should adopt a health equity perspective to ensure that prevention is targeted where people are more likely to engage in suicide ideation.

The Compress® transcutaneous implant for rehabilitation following limb amputation.

Amputation is an unfortunate outcome of a variety of orthopedic conditions. Many amputees can be functionally fitted with conventional suspension sockets. A substantial subset, however, fails this conventional treatment and is unable to function. In Europe, an alternative to socket-based prostheses has been available for 25 years. Patients there who are unable to functionally use socket-based prostheses have been offered the possibility for transcutaneous osseointegration. With this technology, the prosthetic limb can be rigidly attached to the residual bone, and the socket is eliminated, in many cases enabling improved function and patient satisfaction. In the United States, regulatory barriers have greatly limited the adoption and acceptance of transdermal osseointegration. The Compress® device was developed as an alternate means of fixation for massive endoprostheses, such as distal femoral replacements. A uniquely designed prosthesis is rigidly anchored to the end of the cortical bone and is then subjected to a large axial stress. The bone then grows avidly into the device, providing permanent osseointegration. We have recently adopted this device for transcutaneous use. These procedures have been performed in the United States on a custom regulatory basis. Results of this have been encouraging, and we are planning to begin a regulatory trial in the near future.

Preferences for return of incidental findings from genome sequencing among women diagnosed with breast cancer at a young age.

While experts have made recommendations, information is needed regarding what genome sequencing results patients would want returned. We investigated what results women diagnosed with breast cancer at a young age would want returned and why. We conducted 60 semi-structured, in-person individual interviews with women diagnosed with breast cancer at age 40 or younger. We examined interest in six types of incidental findings and reasons for interest or disinterest in each type. Two coders independently coded interview transcripts; analysis was conducted using NVivo 10. Most participants were at least somewhat interested in all six result types, but strongest interest was in actionable results (i.e. variants affecting risk of a preventable or treatable disease and treatment response). Reasons for interest varied between different result types. Some participants were not interested or ambivalent about results not seen as currently actionable. Participants wanted to be able to choose what results are returned. Participants distinguished between types of individual genome sequencing results, with different reasons for wanting different types of information. The findings suggest that a focus on actionable results can be a common ground for all stakeholders in developing a policy for returning individual genome sequencing results.

Search for Sterile Neutrinos Mixing with Muon Neutrinos in MINOS.

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a ν_{µ}-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56×10^{20} protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ_{24} and Δm_{41}^{2} and set limits on parameters of the four-dimensional Pontecorvo-Maki-Nakagawa-Sakata matrix, |U_{µ4}|^{2} and |U_{τ4}|^{2}, under the assumption that mixing between ν_{e} and ν_{s} is negligible (|U_{e4}|^{2}=0). No evidence for ν_{µ}→ν_{s} transitions is found and we set a world-leading limit on θ_{24} for values of Δm_{41}^{2}≲1 eV^{2}.

Viral infections associated with oral cancers and diseases in the context of HIV: a workshop report.

Human herpesviruses (HHVs) and human papillomavirus (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes immunocompromised by age, illness or HIV infection these dormant viruses can manifest and produce disease. In HIV-positive patients, there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses Epstein-Barr Virus, HHV-8 and HPV. This workshop examined four questions regarding the viruses associated with oral cancers and disease in the HIV-positive and -negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required.

Moderators of intervention dose effects on diet quality and physical activity changes in a church-based, multicomponent, lifestyle study: Delta Body and Soul III.

Many community-based lifestyle interventions targeting African Americans have reported positive effects on participants' dietary choices and physical activity habits. However, these effects vary and not all participants will have outcome changes. Moderation analysis can help explain differential effects observed, but are not often reported. Hence, the objective of this secondary analysis was to explore potential moderators of intervention dose effects on diet quality and physical activity outcomes in an effective lifestyle intervention. Delta Body and Soul III, conducted from 2011 to 2012, was a 6-month, church-based, multicomponent, educational intervention designed to improve diet quality and increase physical activity in rural Southern African American adults. Generalized linear mixed models were used to determine associations among indicators of intervention dose received by participants, potential moderators and health outcome changes. Results indicated only three baseline characteristics-employment status, food shopping frequency and individual with primary responsibility for meal preparation-moderated the effects of education session attendance on diet quality changes. No evidence for moderation of exercise class attendance effects on physical activity changes was found. Thus, this culturally targeted, multicomponent lifestyle intervention did induce positive health changes in participants with a range of sociodemographic characteristics and food shopping and eating behaviors.

Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Cancers among US organ donors: a comparison of transplant and cancer registry diagnoses.

Transmission of cancer is a life-threatening complication of transplantation. Monitoring transplantation practice requires complete recording of donor cancers. The US Scientific Registry of Transplant Recipients (SRTR) captures cancers in deceased donors (beginning in 1994) and living donors (2004). We linked the SRTR (52,599 donors, 110,762 transplants) with state cancer registries. Cancer registries identified cancers in 519 donors: 373 deceased donors (0.9%) and 146 living donors (1.2%). Among deceased donors, 50.7% of cancers were brain tumors. Among living donors, 54.0% were diagnosed after donation; most were cancers common in the general population (e.g. breast, prostate). There were 1063 deceased donors with cancer diagnosed in the SRTR or cancer registry, and the SRTR lacked a cancer diagnosis for 107 (10.1%) of these. There were 103 living donors with cancer before or at donation, diagnosed in the SRTR or cancer registry, and the SRTR did not have a cancer diagnosis for 43 (41.7%) of these. The SRTR does not record cancers after donation in living donors and so missed 81 cancers documented in cancer registries. In conclusion, donor cancers are uncommon, but lack of documentation of some cases highlights a need for improved ascertainment and reporting by organ procurement organizations and transplant programs.

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

BACKGROUND: Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution. SUBJECTS/METHODS: In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case-control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry. RESULTS: In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P < 0.01), adiponectin was significantly lower in AA men and women (P = 0.02 and P < 0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P < 0.0001) and CRP (P = 0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status. CONCLUSIONS: These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation to disparities in obesity-related disease risk.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Combined analysis of νµ disappearance and νµâ†’νe appearance in MINOS using accelerator and atmospheric neutrinos.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(µ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.28-2.46] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and |Δm(32)(2)| = [2.32-2.53] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ(CP), the θ(23} octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

A phase II study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients with progressive, metastatic, castration-resistant prostate cancer.

BACKGROUND: This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent. PATIENTS AND METHODS: The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA50) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA50 response in Arm B. RESULTS: In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC. CONCLUSIONS: Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.

HPV-related cancers after solid organ transplantation in the United States.

Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva and oropharynx. We examined the incidence of HPV-related cancers in 187 649 US recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRRs) compared rates across transplant subgroups. We observed elevated incidence of HPV-related cancers (SIRs: in situ 3.3-20.3, invasive 2.2-7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal and penile cancers (IRRs 2.1-4.6 for 5+ vs. <2 years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13 and increased incidence with B:44, contributed to susceptibility at several sites. Use of specific immunosuppressive medications was variably associated with incidence; for example, tacrolimus, was associated with reduced incidence for some anogenital cancers (IRRs 0.4-0.7) but increased incidence of oropharyngeal cancer (IRR 2.1). Thus, specific features associated with recipient characteristics, transplanted organs and medications are associated with incidence of HPV-related cancers after transplant. The absence of increased incidence of invasive cervical cancer highlights the success of cervical screening in this population and suggests a need for screening for other HPV-related cancers.

Electron neutrino and antineutrino appearance in the full MINOS data sample.

We report on ν(e) and ν(e) appearance in ν(µ) and ν(µ) beams using the full MINOS data sample. The comparison of these ν(e) and ν(e) appearance data at a 735 km baseline with θ13 measurements by reactor experiments probes δ, the θ23 octant degeneracy, and the mass hierarchy. This analysis is the first use of this technique and includes the first accelerator long-baseline search for ν(µ) → ν(e). Our data disfavor 31% (5%) of the three-parameter space defined by δ, the octant of the θ23, and the mass hierarchy at the 68% (90%) C.L. We measure a value of 2sin(2)(2θ13)sin(2)(θ23) that is consistent with reactor experiments.