From epidemic to pandemic: Effects of the COVID-19 outbreak on high school program choices in Sweden.

We study whether the onset of the COVID-19 crisis affected the program choices of high school applicants in Sweden. Our analysis exploits the fact that the admission process consists of two stages: a preliminary round in which applicants initially rank programs in order of preference and a final round in which they can alter their preliminary rankings. In 2020, the timing of the two rounds happened to provide a unique pre- and post-crisis snapshot of applicants' field-of-study choices. Using school-level data on applicants' top-ranked programs for all admission rounds between 2016 and 2020, we implement a difference-in-differences method to identify the immediate effect of the crisis on demand for programs. We find no change in demand for academic programs, but a decline in top-ranked applications to some of the vocational programs. The declines are most pronounced and robust for programs related to the Accommodation and Food Services sector, which was the most adversely affected industry during the crisis. This finding suggests that labor market considerations influence the study choices made by relatively young students.

Clinical outcomes in ovarian cancer patients receiving three versus more cycles of chemotherapy after neoadjuvant treatment and interval cytoreductive surgery.

OBJECTIVES: To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy. METHODS: We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively. RESULTS: A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities. CONCLUSIONS: Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment.

Efficacy of feed additives to reduce the effect of naturally occurring mycotoxins fed to turkey hen poults reared to 6 weeks of age.

Corn with naturally occurring aflatoxin (AF), wheat with naturally occurring doxynivalenol (DON), and barley with naturally occurring zearalenone (ZEA) were used to make rations for feeding turkey hen poults to 6 weeks of age. Control rations with equal amounts of corn, wheat, and barley were also fed. The control rations did contain some DON while both sets of rations contained ZEA. Within each grain source, there were 4 treatments: the control ration plus 3 rations each with a different feed additive which were evaluated for the potential to lessen potential mycotoxin effects on bird performance and physiology. The additives were Biomin BioFix (2 lb/ton), Kemin Kallsil (4 lb/ton), and Nutriad UNIKE (3 lb/ton). The mycotoxin rations reduced poult body weight (2.31 vs. 2.08 ± 0.02 kg) and increased (worsened) poult feed conversion (1.47 vs. 1.51 ± 0.01) at 6 wk. Feeding the poults the mycotoxin feed also resulted in organ and physiological changes typical of feeding dietary aflatoxin although a combined effect of AF, DON, and ZEA which cannot be dismissed. The feed additives resulted in improved feed conversion to 6 wk in both grain treatment groups. The observed physiological effect of feeding the additives was to reduce relative gizzard weight for both groups and to lessen the increase in relative kidney weight for the birds fed the mycotoxin feed. In conclusion, the feed additives used in this study did alleviate the effect of dietary mycotoxins to some degree, especially with respect to feed conversion. Further studies of longer duration are warranted.

Effect of tear size, corticosteroids and subacromial decompression surgery on the hierarchical structural properties of torn supraspinatus tendons.

OBJECTIVES: The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. METHODS: Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. RESULTS: Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. CONCLUSIONS: These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252-61.

Tenocyte proliferation on collagen scaffolds protects against degradation and improves scaffold properties.

Tissue engineering scaffolds encourage cell proliferation whilst degrading to facilitate tissue regeneration. Their mechanical properties therefore change, decreasing due to scaffold degradation and increasing due to extracellular matrix deposition. This work compares the changing properties of collagen scaffolds incubated in culture medium, with and without human tenocytes, in order to investigate the relationship between degradation and tenocyte proliferation. The material properties of scaffolds are compared over 26 days using mechanical testing, differential scanning calorimetry, infra-red spectroscopy, and histology and biochemical assays. For medium-only scaffolds, the mechanical properties decrease rapidly, while culture medium sulfhydryl content increases significantly, with no significant changes in the denaturation temperature of scaffold collagen content. Conversely, the mechanical properties and collagen content of tenocyte-seeded scaffolds increase significantly while culture medium sulfhydryl content decreases and denaturation temperature remains the same. These results indicate that tenocytes proliferation both reduces the degradation of collagen scaffolds incubated in culture medium and produces scaffolds with improved properties.

Atomic Force Microscopy of bulk tendon samples: affect of location and fixation on tissue ultrastructure.

Atomic Force Microscopy (AFM) is a surface characterisation technique which analyses topology. To date, AFM studies of tissue ultrastructure have focussed on single collagen fibrils extracted from different tissues prior to analysis. Using sample preparation techniques used in electron microscopy studies, this work uses AFM to analyse the collagen ultrastructure of bulk samples from bovine deep digital flexor tendons (DDFTs). DDFT ultrastructure in regions of the tendon which experience different loading conditions are compared. Samples are analysed post-freezing and post-aldehyde fixation with either 10% formalin or 4% glutaraldehyde in order to investigate the affect of tissue preservation on tissue ultrastructure. The results demonstrate that both fibril diameter and repeat unit of the tendon vary between different regions in the dorsoventral plane, with regions subjected to both tensile and compressive forces exhibiting smaller fibril diameter and repeat unit compared to regions subjected to tensile forces alone. These differences are detectable regardless of the tissue preservation technique used. However these measured differences do vary with preservation techniques with aldehyde-fixed samples exhibiting smaller fibril diameters and larger repeat units compared to frozen samples. These results demonstrate that AFM is a highly suitable technique for the characterisation of different ultrastructures in bulk samples but that it is important to be consistent in the choice of preservation technique.

Pancreatitis in HIV infection: predictors of severity.

OBJECTIVES: Acute pancreatitis occurs at greater frequency in HIV-infected patients than in the general population. We set out to determine the frequency of severe acute pancreatitis in HIV-positive patients and to study the accuracy of The Acute Physiology and Chronic Health Evaluation (APACHE II), Ranson, and Glasgow scales for prediction of clinical disease severity. METHODS: A total of 73 HIV-infected patients with acute pancreatitis were identified retrospectively. Demographic and clinical parameters as well as clinical outcomes were established. Sensitivities and specificities of the three scales mentioned above were calculated and compared. RESULTS: Of the patients, 63 (83.6%) had AIDS. The majority of cases were medication-induced (46%) or idiopathic (26%). The incidence seemed to be declining in the late 1990s. Eleven patients (15%) had a severe course as defined by death, admission to the intensive care unit, or local complications requiring surgery. Eighteen case (24.6%) were considered severe as defined by the criteria established at the International Symposium on Acute Pancreatitis in Atlanta in 1992. APACHE II criteria best predicted outcome with an overall accuracy of 75% (Glasgow 69%, Ranson 48%). Maximal accuracy was achieved with cut-offs of 14 for APACHE II and 4 for the Glasgow and Ranson criteria. CONCLUSIONS: HIV-infected patients have a clinical outcome similar to that of the general population. Clinical predictive scales are applicable and useful in this population.

Clinical and histological predictors of response to medical therapy in collagenous colitis.

OBJECTIVES: Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can predict response to medical therapy. METHODS: All cases of CC were identified in three tertiary care medical centers. All charts of included patients were reviewed and clinical variables (age, gender, duration of symptoms, frequency of bowel movements, and the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) were recorded. Available histology slides were reviewed by one GI pathologist. Intraepithelial inflammation, epithelial loss or detachment, inflammation in the lamina propria, presence of eosinophilia, crypt inflammation, Paneth's cell metaplasia, and collagen layer thickness were recorded. Depending on their response to therapy, patients were divided into three groups: 1) spontaneous recovery or response to antidiarrheal agents alone, 2) response to 5-ASA agents, and 3) response to corticosteroids after failure of antidiarrheal agents and 5-ASA. RESULTS: Ninety-four patients with CC were identified. Of these, 62 patients were included. The median age was 58 (range = 20-85), and 88% were female. Among the histological parameters only the degree of inflammation in the lamina propria significantly differed between the three response groups (p = 0.007). Patients who required corticosteroids had greater inflammation. Among the clinical parameters age at presentation and use of NSAIDs significantly differed between groups. In the antidiarrheal group, patients tended to be more elderly, and in the corticosteroid group, more patients were on NSAIDs. CONCLUSIONS: 1) The degree of lamina propria inflammation can be used as a histological predictor to guide treatment in patients with CC. 2) Patients who responded to antidiarrheal agents or had spontaneous remissions were significantly older than those patients requiring 5-ASA compounds or corticosteroids. 3) Patients who were taking NSAIDs were more likely to require corticosteroid therapy, presumably reflecting more severe disease.

Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule.

The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.

Multiple organ dysfunction: baseline and serial component scores.

OBJECTIVE: The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU. DESIGN: Prospective observational cohort study. SETTING: Sixteen Canadian ICUs. PATIENTS: A total of 1,200 patients were mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9-1.4]; week 2 onward: RR, 1.9 [1.5-2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0-1.5]; week 2 onward: RR, 1.7 [1.4-2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1-3: RR, 0.9 [0.7-1.1]; week 4 onward: RR, 1.4 [1.0-2.0]). CONCLUSIONS: Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.

Firearms risk management in psychiatric care.

OBJECTIVE: This study sought to assess the effectiveness of a firearms risk management program. METHODS: A firearms risk management program, which included multidisciplinary assessment, treatment, and discharge planning, was developed and implemented among 46 civilly committed psychiatric inpatients at the Twin Valley Psychiatric System, a behavioral health organization of the Ohio Department of Mental Health. RESULTS: The research sample comprised mainly men who had personality disorders and histories of substance abuse and who had expressed an intent to use a firearm to commit suicide. On discharge, none of the patients had access to a firearm. Of the 16 patients who were hospitalized during the next 24 months, only five were noted to have threatened to harm themselves or others with a firearm or to have access to a firearm. CONCLUSIONS: Multidisciplinary and focused assessment, treatment, and discharge planning can be effective in neutralizing the risk of firearms use among psychiatric patients.

Imide and lactam derivatives of N-benzylpyroglutamyl-L-phenylalanine as VCAM/VLA-4 antagonists.

A series of imides and lactams derived from 4-amino-N-benzylpyroglutamyl-L-phenylalanine was prepared and evaluated for activity as VCAM/VLA-4 antagonists. Imides were more potent than the corresponding lactams; several had subnanomolar IC50s in an ELISA based assay and were also highly effective at blocking VLA-4 expressing Ramos cell binding to VCAM coated plates.

Carbacyclic peptide mimetics as VCAM-VLA-4 antagonists.

Substitution of carbon for sulfur in a potent 13-membered cyclic disulfide containing peptide was accomplished via an intramolecular Wittig reaction and resulted in a series of 'carba' analogues. Potency in the VCAM-VLA-4 assay was sensitive to ring size and lower than that of the parent disulfide.

Cyclic thioether peptide mimetics as VCAM-VLA-4 antagonists.

Selective substitution of a sulfur atom by carbon in a highly potent 13-membered cyclic disulfide was accomplished by intramolecular displacement of a bromide. The potency of the resulting thioethers in the VCAM/VLA-4 assay was dependent on ring size and the position of the sulfur atom.

The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic.

The Asp-Pro sequence of the cyclic peptide Ac-HN-Tyr-Cys*-Asp-Pro-Cys*-OH (1) could be replaced with the achiral dipeptide mimetic 1-(2-aminoethyl)cyclpentylcarboxylic acid with retention of potent inhibition of the VCAM-VLA-4 interaction.

N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.

A series of N-(N-benzylpyroglutamyl)-4-substituted-L-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. Analogues substituted by electron deficient benzoylamino groups bearing bulky ortho substituents had low-nM potency in an ELISA assay and low-microM activity in a cell based assay.

N-acyl phenylalanine analogues as potent small molecule VLA-4 antagonists.

We have identified a series of low molecular weight (Mr < 500) N-acylphenylalanines that are effective inhibitors of the VCAM-VLA-4 interaction. Investigation of the SAR of the N-acyl moiety led to the identification of N-benzylpyroglutamyl derivatives as being particularly potent.

Effects of Two Carbamates on Infective Juveniles of Stemernema carpocapsae All Strain and Steinernema feltiae Umeå Strain.

Laboratory bioassays were conducted to determine the effects of two carbamates, carbofuran (an acetylcholinesterase inhibitor) and fenoxycarb (a juvenile hormone analog), on survival and infectivity of the infective juveniles (IJ) of Steinernema feltiae Umeå strain and Steinernema carpocapsae All strain. Both insecticides caused mortality of IJ in a dose-related fashion. The two nematode species were equally sensitive to fenoxycarb (LD ca. 0.03mg/ml). Whereas IJ of S. feltiae were several orders of magnitude more sensitive to carbofuran (LD

Scratching the surface: mental health training for rural health workers.

This paper will describe the Mental Health Training for Rural Health Workers Project that was completed in 1995 under the Rural Health Support Education and Training Program. The lack of specialist mental health services in rural areas means that generalist health workers need to provide mental health services in rural communities. Generalist health workers often feel ill-equipped to help people who require mental health services. The aim of this project was to provide generalist workers in rural areas with practical skills and knowledge in order to help people with mental health disorders and promote positive mental health. The project involved an initial needs survey, the development of education and training material, the implementation of the training, and evaluation of the project.