Recent advances in immune-based approaches for the treatment of esophagogastric cancer.

INTRODUCTION: The year 2021 will be remembered as a transformational year in the management of both esophageal and gastric cancers. Decades of failed clinical trials had seen limited therapeutic advances beyond refinement of the traditional combined modality approach. Targeted strategies against specific molecular alterations did not - with the exception of Her2 - yield the desired breakthroughs, and it was unclear what immune-based approaches would bring to this group of cancers. The presence of tumor-infiltrating lymphocytes in esophagogastric cancer demonstrates that an endogenous immune response is already occurring and potentially amplifiable by immune checkpoint inhibition. Recent data have validated this with FDA approvals in both the locoregional (CheckMate 577) and metastatic disease (CheckMate 649, KeyNote 590 and KeyNote 811) setting which have altered the therapeutic landscape. AREAS COVERED: Here we discuss recent data and ongoing research efforts to better define the role of immune-based approaches and select the patient cohorts who might gain the most benefit from them. EXPERT OPINION: Immunotherapy, and specifically the incorporation of the immune checkpoint inhibitors (ICI) drug class, has altered the therapeutic paradigm of many cancers in recent years. Anti-PD-1 therapies are now the new standard of care for patients with local and advanced disease.

The feasibility and effectiveness of a novel online mental health literacy course in supporting university student mental health: a pilot study.

BACKGROUND: There is a need for effective universal approaches to promote and support university student mental health that are scalable and sustainable. In this pilot study we assess the feasibility and acceptability of a fully-digitalized, comprehensive mental health literacy course co-created with and tailored to the needs of undergraduate students. We also explore preliminary associations with mental health and positive behaviour change. METHODS: An accredited online mental health literacy course was developed using state-of-the-art pedagogical principles and a reverse mentorship approach. The course was offered as an interdisciplinary undergraduate elective. Students completed an online survey before and after the 12-week course that collected demographic information and assessed mental health knowledge, emotional self-awareness, mental health, stigma, and health-related behaviors using validated measures. Dependent group t-tests were used to compare pre- and post-course levels of knowledge, mental health, sleep quality and substance use. Mental health outcomes of students who completed the course were compared to an age and sex-matched sample of students not enrolled in the course and who completed the same survey measures over the same academic year. Multivariable linear regression was used to examine the effect of course participation on outcomes at follow-up. RESULTS: The course had good uptake and was positively reviewed by participants. Specifically, students found the course engaging, relevant, and applicable, and agreed they would recommend it to their peers. Among course participants there was improvement in mental health knowledge (p < 0.001) and emotional self-awareness (p = 0.02) at course completion. Compared to the matched comparison group, taking the course was associated with reduced alcohol (ß = - 0.41, p = 0.01) and cannabis use (ß = - 0.35, p = 0.03), and improved sleep quality (ß = 1.56, p = 0.09) at the end of the term. CONCLUSIONS: Findings suggest that delivering mental health literacy as an online accredited course may be an acceptable and effective way of promoting university student mental health through improved knowledge, emotional self-awareness, and healthy lifestyle choices. As the course is expanded to larger and more diverse student cohorts we will be able to further examine the short and long-term effectiveness of the course in supporting student mental health and the underlying mechanisms.

The numerical translation of verbal probability expressions by patients and clinicians in the context of peri-operative risk communication.

Shared decision-making is central to the pre-operative consent process and accurate communication of risk is dependent on a clear understanding of numerical information by both the patient and clinician. The risk of an adverse event or complication is often described using verbal probability expressions but how these are interpreted by clinicians and patients in the pre-operative setting has not been studied. We asked patients and clinicians to assign a numerical translation (as a percentage) for seven verbal probability expressions in relation to the probability of a major peri-operative complication occurring. In total, data from 290 patients and 57 clinicians were analysed. There was a wide range in percentages assigned by patients to all verbal probability expressions. Patients assigned a wider range of percentage values to each of the verbal probability expressions and these were all significantly higher than those assigned by clinicians: median (IQR [range]) negligible risk 5% (1-15 [0-100]) vs. 0% (0-0 [0-5]); minimal risk 5% (2-10) [0-100]) vs. 1% (0-1 [0-10]); low risk 10% (3-10 [0-100]) vs. 1% (0-2) [0-10]); standard risk 20% (10-40) [0-100]) vs. 1% (1-5) [0-30]); moderate risk 33% (20-50) [0-100]) vs. 5% (3-10) [0-80]); high risk 70% (30-90 [0-100]) vs. 15% (10-40) [1-75]); and very high risk 90% (50-95 [0-100]) vs. 40% (20-50 [5-100]), respectively (p < 0.005 for all comparisons). There is considerable variation in the numerical translation of verbal probability expressions by both patients and clinicians. This suggests that verbal probability expressions should not be used in isolation as part of doctor-patient discussions regarding peri-operative risk.

Measuring the shielding properties of flexible or rigid enclosures for portable electronics.

Heaviside, in volume 1 of Electromagnetic theory, considered shielding of conducting materials in the form of attenuation. This treatment is still significant in the understanding of shielding effectiveness. He also considered propagation of electromagnetic waves in free-space. What Heaviside (1850-1925) could never have imagined is that 125 years later, there would be devices we know as mobile phones (or cell phones, handies, etc.) with capabilities beyond the dreams of the great science fiction writers of the day like H. G. Wells (1866-1949) or Jules Verne (1828-1905). More than this, that there would be a need for law enforcement agencies, among others, to use electromagnetically shielded enclosures to protect electronic equipment from communicating with the 'outside world'. Nevertheless, Heaviside's work is still fundamental to the developments discussed here. This paper provides a review of Heaviside's view of shielding and propagation provided in volume 1 of Electromagnetic theory and develops that to the design of new experiments to test the shielding of these portable enclosures in a mode-stirred reverberation chamber, a test environment that relies entirely on reflections from conducting surfaces for its operation.This article is part of the theme issue 'Celebrating 125 years of Oliver Heaviside's 'Electromagnetic Theory''.

Treating Hepatobiliary Cancer: The Immunologic Approach.

Hepatobiliary cancer comprises a heterogeneous group of malignancies in which the standard treatments for advanced disease are minimally effective and evolve slowly over time. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches is yet to be experienced. Notwithstanding this, the etiological background of hepatobiliary cancer - overlapping in almost every known causative or associated factor with inflammation - provides a strong clue that these approaches may have an impact on this group of diseases. This review seeks to put the management of hepatobiliary cancers in the context of its inflammation-based etiology, with the aim of pointing to the therapeutic opportunities in immune-based approaches currently entering the clinic or those that are about to do so.

Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer.

The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis.

A single-center evaluation of the risk for colonization or bacteremia with piperacillin-tazobactam- and cefepime-resistant bacteria in patients with acute leukemia receiving fluoroquinolone prophylaxis.

Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum ß-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant organism. However, prompt de-escalation of carbapenem therapy needs to be reiterated within hospital practice.

Immunological off-target effects of standard treatments in gastrointestinal cancers.

The effects on immune cells and the inflammatory microenvironment of commonly applied cancer treatments (chemotherapeutic or biologic agents, interventional radiologic procedures) have become better appreciated. Likewise, the contribution of the immune system toward the effectiveness of these treatments is clearer. The relevance of immune evasion by developing tumors is endorsed by its inclusion as one of the (updated) hallmarks of cancer. A greater understanding of this dimension can potentially lead to novel applications of existing standard of care therapies, in addition to potentiating their effect. This review summarizes the immune aspects of currently employed therapies-cytotoxic chemotherapeutics, biologic agents and interventional radiologic procedures-in solid tumor malignancies with a particular focus on those agents used in gastrointestinal cancers.

Association between maternal body mass index during pregnancy, short-term morbidity, and increased health service costs: a population-based study.

OBJECTIVE: To investigate the impact of maternal body mass index (BMI, kg/m(2)) on clinical complications, inpatient admissions, and additional short-term costs to the National Health Service (NHS) in Scotland. DESIGN: Retrospective cohort study using an unselected population database. SETTING: Obstetric units in Scotland, 2003-2010. POPULATION: A total of 124,280 singleton deliveries in 109,592 women with a maternal BMI recorded prior to 16 weeks of gestation. METHODS: Population-based retrospective cohort study of singleton deliveries, with multivariable analysis used to assess short-term morbidity and health service costs. MAIN OUTCOME MEASURES: Maternal and offspring outcomes, number and duration of hospital admissions, and healthcare costs. RESULTS: Using multivariable analysis, in comparison with women of normal weight, women who were overweight, obese, or severely obese had an increased risk of essential hypertension [1.87 (1.18-2.96), 11.90 (7.18-19.72), and 36.10 (18.33-71.10)], pregnancy-induced hypertension [1.76 (1.60-1.95), 2.98 (2.65-3.36), and 4.48 (3.57-5.63)], gestational diabetes [3.39 (2.30-4.99), 11.90 (7.54-18.79), and 67.40 (37.84-120.03)], emergency caesarean section [1.94 (1.71-2.21), 3.40 (2.91-3.96), and 14.34 (9.38-21.94)], and elective caesarean section [2.06 (1.84-2.30), 4.61 (4.06-5.24), and 17.92 (13.20-24.34)]. Compared with women of normal weight, women who were underweight, overweight, obese, or severely obese were associated with an 8, 16, 45, and 88% increase in the number of admissions, respectively, and women who were overweight, obese, or severely obese were associated with a 4, 9, and 12% increase in the duration of stay (all P < 0.001). The additional maternity costs [mean (95% CI), adjusted analyses] for women who were underweight, overweight, obese, or severely obese were £102.27 (£48.49-156.06), £59.89 (£41.61-78.17), £202.46 (£178.61-226.31), and £350.75 (£284.82-416.69), respectively. CONCLUSIONS: Maternal BMI influences maternal and neonatal morbidity, the number and duration of maternal and neonatal admissions, and health service costs.

Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter.

There is evidence that vasoactive intestinal polypeptide (VIP) participates in inhibitory neuromuscular transmission (NMT) in the internal anal sphincter (IAS). However, specific details concerning VIP-ergic NMT are limited, largely because of difficulties in selectively blocking other inhibitory neural pathways. The present study used the selective P2Y1 receptor antagonist MRS2500 (1 µm) and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine (l-NNA; 100 µm) to block purinergic and nitrergic NMT to characterize non-purinergic, non-nitrergic (NNNP) inhibitory NMT and the role of VIP in this response. Nerves were stimulated with electrical field stimulation (0.1-20 Hz, 4-60 s) and the associated changes in contractile and electrical activity measured in non-adrenergic, non-cholinergic conditions in the IAS of wild-type and VIP(-/-) mice. Electrical field stimulation gave rise to frequency-dependent relaxation and hyperpolarization that was blocked by tetrodotoxin. Responses during brief trains of stimuli (4 s) were mediated by purinergic and nitrergic NMT. During longer stimulus trains, an NNNP relaxation and hyperpolarization developed slowly and persisted for several minutes beyond the end of the stimulus train. The NNNP NMT was abolished by VIP6-28 (30 µm), absent in the VIP(-/-) mouse and mimicked by exogenous VIP (1-100 nm). Immunoreactivity for VIP was co-localized with neuronal nitric oxide synthase in varicose intramuscular fibres but was not detected in the VIP(-/-) mouse IAS. In conclusion, this study identified an ultraslow component of inhibitory NMT in the IAS mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged period of anal relaxation.

Second-line treatment in advanced pancreatic cancer: a comprehensive analysis of published clinical trials.

BACKGROUND: There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. The aim of this analysis was to compare the different therapeutic approaches in this setting. METHODS: We carried out a systematic analysis of second-line studies in advanced pancreatic cancer that have progressed on or following gemcitabine and published or presented from 2000 to 2012. RESULTS: Forty-four clinical trials (t) were identified; of which 34 met the inclusion criteria treating an aggregate total of 1503 patients (n). Patients who received treatments (t: 33; n: 1269) had a median overall survival (OS) of 6 months compared with 2.8 months for patients who received best supportive care only (t: 2; n: 234) (P = 0.013). The gemcitabine and platinum-based combination (t: 5; n: 154) provided a median progression-free survival and OS of 4 and 6 months compared with 1.6 and 5.3 for the rest of the regimens (t: 29; n: 1349) (P = 0.059 and 0.10, respectively) and 2.9 and 5.7 for the combination of 5-fluorouracil and platinum agents (t: 12; n: 450) (P = 0.60 and 0.22, respectively). CONCLUSION(S): Although not conclusive, these data showed that the advantage of second-line chemotherapy in pancreatic cancer is very limited and there is a need for more studies.

Nonsteroidal anti-inflammatory drug use in collegiate football players.

OBJECTIVE: To determine prevalence of nonsteroidal anti-inflammatory drug (NSAID) use in college football players and whether positions sustaining the most contact would use NSAIDs more frequently. DESIGN: Prospective cross-sectional study. SETTING: American college football programs. PATIENTS: An anonymous survey was given to 211 college football players before the season. INDEPENDENT VARIABLE: Use of NSAIDs. MAIN OUTCOME MEASURES: The dependent variables are the different patterns in NSAID usage among positions and the frequency of NSAID use before and after the season. RESULTS: Of the athletes surveyed, 95.7% had or were using NSAIDs. Athletes first used NSAIDs in junior high school (45.6%), high school (48.5%), or college (5.8%). Athletes were separated into high (daily or weekly) or low (monthly or rarely) utilizers of NSAIDs. High utilization of NSAIDs was more frequent during the season (50.0%) than in the off-season (14.6%), P < 0.001. High NSAID utilization among all players was more prevalent after than before games (32.7% vs 10.9%, P = 0.002). Players with a higher body mass index (BMI; >28) were significantly higher utilizers of NSAIDs, reporting higher rates of use in season compared with other players (57.4% vs 39.5%, P = 0.011, OR = 2.06). CONCLUSIONS: Use of NSAIDs in collegiate football players is common. It is concerning that those athletes with the highest cardiovascular risk (ie, elevated body mass index) use greater amounts of NSAIDs. Further investigation is needed to delineate the short-term and long-term consequences of NSAID utilization in young athletes.

Mental health and academic outcomes over the first year at university in international compared to domestic Canadian students.

OBJECTIVE: To compare risk factors and associated mental health and academic outcomes between international and domestic students. PARTICIPANTS: Canadian university undergraduate students. METHODS: Electronic surveys were completed at university entry and the end of first year. Surveys assessed demographics, risk factors, symptoms of mental disorders, and access to support. Academic outcomes were obtained from university databases. RESULTS: International students had comparable or lower rates of clinically significant anxiety, depression, and insomnia. Domestic female students reported the highest screening rates for common mental disorders. However, international students were more likely to report having attempted suicide. International students felt less connected to the university community and had lower academic performance. Psychosocial risk factor profiles and proportions accessing mental health services were similar. CONCLUSIONS: The scope of mental health need appears more similar than different between international and domestic students; however, international students may benefit from targeted academic and social support initiatives.

Investigating a clinically actionable BRAF mutation for monitoring low-grade serous ovarian cancer: A case report.

Low-grade serous ovarian cancer (LGSOC) poses a specific clinical challenge due to advanced presentation at diagnosis and the lack of effective systemic treatments. The aim of this study was to use a precision medicine approach to identify clinically actionable mutations in a patient with recurrent LGSOC. Primary, metastatic and recurrence tissue, and blood samples were collected from a stage IV LGSOC patient. Single-gene testing for clinically actionable mutations (BRAF V600, KRAS and NRAS) and subsequent whole-exome sequencing (WES) were performed. Droplet digital PCR was used to evaluate the presence of an identified BRAF D594G mutation in the matched plasma cell-free DNA (cfDNA). No clinically actionable mutations were identified using single-gene testing. WES identified a BRAF D594G mutation in six of seven tumor samples. The patient was commenced on a MEK inhibitor, trametinib, but with minimal clinical response. A newly designed ddPCR assay detected the BRAF alteration in the matched tissues and liquid biopsy cfDNA. The identification and sensitive plasma detection of a common "druggable" target emphasises the impact of precision medicine on the management of rare tumors and its potential contribution to novel monitoring regimens in this field.

Two cases of unexpected long-term improvement of Parkinson's disease after subthalamic nucleus deep brain stimulation removal.

Two patients with Parkinson's disease (PD) treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS) for 3-4 years are reported, who demonstrated a persistent improvement following removal of STN-DBS for late infection. Possible hypotheses are discussed--whether a microlesioning effect or a disease-modifying effect of STN-DBS, though neither adequately explain this phenomenon.

Measurement at the field scale of soil delta13C and delta15N under improved grassland.

Variations in natural abundance of carbon (C) and nitrogen (N) stable isotopes are widely used as tools for many aspects of scientific research. By examining variations in the ratios of heavy to light stable isotopes, information can be obtained as to what physical, chemical and biological processes may be occurring. The spatial heterogeneity of soil delta(15)N- and delta(13)C-values across a range of scales and under different land use have been described by a number of researchers and the natural abundances of the C and N stable isotopes in soils have been found to be correlated with many factors including hydrology, topography, land use, vegetation cover and climate. In this study the Latin square sampling +1 (LSS+1) sampling method was compared with a simple grid sampling approach for delta(13)C and delta(15)N measurement at the field scale. A set of 144 samples was collected and analysed for delta(15)N and delta(13)C from a 12 x 12 grid (in a 1 ha improved grassland field in south-west England). The dimension of each cell of the grid was approximately 11 x 6 m. The 12 x 12 grid was divided into four 6 x 6 grids and the LSS+1 sampling technique was applied to these and the main 12 x 12 grid for a comparison of sample means and variation. The LSS+1 means from the 12 x 12 grid and the four 6 x 6 grids compared well with the overall grid mean because of the low variation within the field. The LSS+1 strategy (13 samples) generated representative samples from the 12 x 12 grid, and hence would be an acceptable method for sampling similar plots for the measurement of mean isotopic composition.

Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte-colony stimulating factor.

Previously, dogs with canine parvovirus-induced neutropenia have not responded to treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF). However, recombinant canine G-CSF (rcG-CSF) has not been previously evaluated for treatment of parvovirus-induced neutropenia in dogs. We assessed the effectiveness of rcG-CSF in dogs with parvovirus-induced neutropenia with a prospective, open-label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG-CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG-CSF. We found that mean WBC and neutrophil counts were significantly higher (P < 0.05) in the 28 dogs treated with rcG-CSF compared to disease-matched dogs not treated with rcG-CSF. In addition, the mean duration of hospitalization was reduced (P = 0.01) in rcG-CSF treated dogs compared to untreated dogs. However, survival times were decreased in dogs treated with rcG-CSF compared to untreated dogs. These results suggest that treatment with rcG-CSF was effective in stimulating neutrophil recovery and shortening the duration of hospitalization in dogs with parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.

Pre-pubertal bipolar disorder: origins and current status of the controversy.

BACKGROUND: Evidence from epidemiological, clinical and high-risk studies has established that the peak period of risk for onset of bipolar disorder spans late adolescence and early adulthood. However, the proposal of the existence of a pre-pubertal form of bipolar disorder manifesting in early childhood created substantial debate. In this narrative review, the literature and contributing factors pertaining to the controversy surrounding the proposed pre-pubertal bipolar disorder subtype are discussed. The resolution of the debate and lessons learned are highlighted. MAIN BODY: In the mid 1990s US researchers proposed that chronic irritability and explosive temper in pre-pubertal children with pre-existing ADHD and/or other learning and developmental disorders might represent a variant of mania. A number of factors contributed to this proposal including severely ill children with no diagnostic home given changes in the ADHD DSM diagnostic criteria and over-reliance on symptoms and structured interviews rather than on a clinical assessment incorporating developmental history, social context and clinical course. Prospective studies of children at high familial risk did not support the proposed pre-pubertal bipolar phenotype; but rather provided convergent evidence that bipolar disorder onset in adolescence and early adulthood not uncommonly preceded by sleep and internalizing symptoms and most often debuting as depression in adolescence (after puberty). Epidemiological studies of population and hospital discharge data provided evidence that the pre-pubertal bipolar phenotype was largely a US driven phenomenon. CONCLUSIONS: Psychiatric diagnosis is particularly challenging given the current lack of objective biomarkers. However, validity and utility of clinical diagnoses can be strengthened if all available predictive information is used to formulate a diagnosis. As in other areas of medicine, critical information required to make a valid diagnosis includes developmental history, clinical course, family history and treatment response-weighed against the known trajectories of classical disorders. Moreover, given that psychiatric disorders are in evolution over childhood and adolescence and symptoms, in of themselves, are often non-specific, a thorough clinical assessment incorporating collateral history and psychosocial context is paramount. Such an approach might have avoided or at least brought a more timely resolution to the debate on pre-pubertal mania.

Predictors of mental health and academic outcomes in first-year university students: Identifying prevention and early-intervention targets.

BACKGROUND: Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts. AIMS: To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes. METHOD: Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders. RESULTS: In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being. CONCLUSIONS: Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.

Pancreatic adenocarcinoma in a young patient population--12-year experience at Memorial Sloan Kettering Cancer Center.

BACKGROUND: There is a dearth of data in a younger population of patients with pancreatic ductal adenocarcinoma (PAC) regarding epidemiology, genetics, prognosis, and outcome. This report examines a large cohort of patients with PAC