Physical working conditions and subsequent sickness absence : a record linkage follow-up study among 19-39-year-old municipal employees

Purpose Physical work exposures are associated with sickness absence among older employees. We aimed to examine if they similarly contribute to all-cause sickness absence during early and mid-careers. Methods We used questionnaire data on physical work exposures linked to register data on sickness absence from 3542 municipal employees aged 19-39 years. Follow-up for the number of sickness absence days was 12 months. Exposures to physical workload, occupational environmental hazards, and sedentary work were divided into quartiles. In addition, duration of daily exposure to heavy work was included. Negative binomial regression models were used. Results Higher exposure to physical workload or hazardous exposures was associated with a higher number of sickness absence days. The age and gender adjusted rate ratios for sickness absence days among the participants whose exposure to physical workload was in the highest exposure quartile were 2.1 (95% CI 1.8-2.5) compared with those whose exposure was in the lowest quartile. In addition, rate ratios for sickness absence days among participants who reported that they do heavy physical work 1.1-2.0 h, 2.1-4.0 h or over 4 h daily were 1.6 (1.3-1.9), 1.5 (1.3-1.8) and 1.7 (1.5-2.1), respectively, compared with those who reported not doing physical work. Further adjustment for lifestyle factors or health characteristics attenuated the associations only slightly. Conclusion Exposure to physically demanding work is associated with a higher number of sickness absence days among municipal employees below 40 years of age. Physical working conditions should be considered when aiming to support later work ability.Peer reviewe

Synthetic DNA immunotherapy in biochemically relapsed prostate cancer

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts). Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks. Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50). Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)

Preliminary seismological and geological studies of the San Fernando, California, earthquake of February 9 1971

The San Fernando earthquake was the largest earthquake to occur in the metropolitan Los Angeles area in more than 50 years. It has tentatively been assigned a magnitude, M_L of 6.6, a focal depth of 13.0 km, and an epicentral location about 12 km east of Newhall, California, at 34°24.0'N, 118°23.7'W (Figure 1), but these figures undoubtedly will be modified as further data become available. Although the focal depth is not as well defined as the epicenter, it is consistent with other observations suggesting thrusting on a fault plane dipping north about 45 ° and breaking the surface in the Sylmar-San Fernando area (Figure 1). It should be emphasized that the hypocenter of the main shock represents only the point of initial rupture. Breaking, presumably, then propagated southward and upward from this point, so that the main geological and engineering effects were observed farther south where the fault was shallower and the displacement greater. The location of the main shock is based on readings from permanent stations of the Caltech network, as well as the U. S. Geological Survey station at Point Mugu (SBLG) and the California Department of Water Resources stations at Pyramid (PYR) and Cedar Springs (CSP). Portable Caltech seismographs were installed in the epicentral area as early as 3 hr following the main shock, and, within a few days, there were at least 30 portable units in the region operated by various groups and agencies

Trading Justice for Peace? Reframing reconciliation in TRC processes in South Africa, Canada and Nordic countries

Conflict in its various manifestations continues to be a defining feature in many places throughout the world. In an attempt to address such conflict, various forms of a Truth and Reconciliation Commission (TRC) have been introduced to facilitate the transition from social conflict to a new dispensation. The introduction and subsequent proceedings of TRCs in South Africa, Canada and Norway are widely regarded as good examples of this approach. Against this background, a number of researchers from VID Specialized University and the University of the Western Cape had an exploratory meeting in Oslo in 2018 where the possibility for a joint research project under the broad theme of ‘discourses on reconciliation’ was first discussed. This led to two further research symposia in Cape Town and Tromsø in 2019. With the inclusion of specialists working on the Canadian Truth and Reconciliation process, these meetings demonstrated common ground and a shared understanding of the issues at stake. Moreover, it pointed to the differences between the South African, Canadian and Norwegian Commissions. In comparing the South African, Canadian and Norwegian experiences, researchers identified that these countries were, in fact, at different stages of their respective truth and reconciliation processes. This has prompted scholars to revisit and problematise these processes in relation to ongoing societal challenges. In all cases, it is quite apparent that reconciliation between individuals and groups remains a significant challenge

Trading Justice for Peace? Reframing reconciliation in TRC processes in South Africa, Canada and Nordic countries

Conflict in its various manifestations continues to be a defining feature in many places throughout the world. In an attempt to address such conflict, various forms of a Truth and Reconciliation Commission (TRC) have been introduced to facilitate the transition from social conflict to a new dispensation. The introduction and subsequent proceedings of TRCs in South Africa, Canada and Norway are widely regarded as good examples of this approach. Against this background, a number of researchers from VID Specialized University and the University of the Western Cape had an exploratory meeting in Oslo in 2018 where the possibility for a joint research project under the broad theme of ‘discourses on reconciliation’ was first discussed. This led to two further research symposia in Cape Town and Tromsø in 2019. With the inclusion of specialists working on the Canadian Truth and Reconciliation process, these meetings demonstrated common ground and a shared understanding of the issues at stake. Moreover, it pointed to the differences between the South African, Canadian and Norwegian Commissions. In comparing the South African, Canadian and Norwegian experiences, researchers identified that these countries were, in fact, at different stages of their respective truth and reconciliation processes. This has prompted scholars to revisit and problematise these processes in relation to ongoing societal challenges. In all cases, it is quite apparent that reconciliation between individuals and groups remains a significant challenge

A multidisciplinary treatment of congenitally missing maxillary lateral incisors: a 14-year follow-up case report

Absence of the maxillary lateral incisor creates an aesthetic problem which can be managed in various ways. The condition requires careful treatment planning and consideration of the options and outcomes following either space closure or prosthetic replacement. Recent developments in restorative dentistry have warranted a re-evaluation of the approach to this clinical situation. Factors relating both to the patient and the teeth, including the presentation of malocclusion and the effect on the occlusion must be considered. The objective of this study was to describe the etiology, prevalence and alternative treatment modalities for dental agenesis and to present a clinical case of agenesis of the maxillary lateral incisors treated by the closure of excessive spaces and canine re-anatomization. A clinical case is presented to illustrate the interdisciplinary approach between orthodontics and restorative dentistry for improved esthetic results. In this report, the treatment of a girl with a Class II malocclusion of molars and canines with missing maxillary lateral incisors and convex facial profile is shown. Treatment was successfully achieved and included the space closure of the areas corresponding to the missing upper lateral incisors, through movement of the canines and the posterior teeth to mesial by fixed appliances as well as the canines transformation in the maxillary lateral incisors. This is a 14-year follow-up case report involving orthodontics and restorative dentistry in which pretreatment, posttreatment, and long-term follow-up records for the patient are presented

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high‑resolution population‑based study

Purpose The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain. Methods A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33–C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients’ hospital medical records from all public and private hospitals from two regions in southern Spain. Results There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02–0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis. Conclusions The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.Maria Jose Sanchez Perez is supported by the Andalusian Department of Health: Research, Development, and Innovation Office project grant PI-0152/2017. Miguel Angel Luque-Fernandez is supported by the Spanish National Institute of Health, Carlos III Miguel Servet I Investigator Award (CP17/00206)

Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes

Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 (NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B) associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1) quantitative metabolic traits, 2) anthropometric measures (waist circumference (WC), waist-hip ratio, and BMI), or 3) type 2 diabetes, and central and general overweight and obesity.The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038) and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β) = 3%(1;5(95%CI)), p(additive) = 2.7×10(-3)), an association driven by the male gender (p(interaction) = 0.02). The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5), p(additive) = 2.5×10(-3)) and increased insulin resistance (HOMA-IR) (β = 4%(1;6), p(additive) = 1.5×10(-3)). The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89), p(additive) = 1.7×10(-3), p(interaction) = 1.0×10(-3)), but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes.We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1, NRXN3, MSRA, and TFAP2B in the pathophysiology of obesity

Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma

Epidermal growth factor receptor (EGFR) mutations are a potential predictor of the effectiveness of EGFR inhibitors for the treatment of lung cancer. Although EGFR mutations were reported to occur with high frequency in nonsmoking Japanese adenocarcinoma patients, the exact nature has not been fully elucidated. We examined EGFR gene mutations within exons 18–21 and their correlations to clinico-pathological factors and other genetic alterations in tumour specimens from 154 patients who underwent resection for lung cancer at Kyoto University Hospital. Epidermal growth factor receptor mutations were observed in 60 tumours (39.0%), all of which were adenocarcinoma. Among the patients with adenocarcinoma (n=108), EGFR mutations were more frequently observed in nonsmokers than former smokers or current smokers (83.0, 50.0, 15.2%, respectively), in women than men (76.3 vs 34.0%), in tumours with bronchio-alveolar component than those without bronchio-alveolar component (78.9 vs 42.9%), and in well or moderately differentiated tumours than poorly differentiated tumours (72.0, 64.4, 34.2%). No tumours with EGFR mutations had any K-ras codon 12 mutations, which were well-known smoking-related gene mutations. In conclusion, adenocarcinomas with EGFR mutation had a distinctive clinico-pathological feature unrelated to smoking. Epidermal growth factor receptor mutations may play a key role in the development of smoking-independent adenocarcinoma