Many questions in human health research can only be answered with observational studies. In contrast to controlled experiments or well-planned, experimental randomized clinical trials, observational studies are subject to a number of potential problems that may bias their results.Some of the more important problems affecting observational studies are described and illustrated by examples. Additional information is provided with reference to a selection of the literature.Factors that may bias the results of observational studies can be broadly categorized as: selection bias resulting from the way study subjects are recruited or from differing rates of study participation depending on the subjects' cultural background, age, or socioeconomic status, information bias, measurement error, confounders, and further factors.Observational studies make an important contribution to medical knowledge. The main methodological problems can be avoided by careful study planning. An understanding of the potential pitfalls is important in order to critically assess relevant publications.
Objectives To determine cancer mortality compared with the general population and to examine dose-response relationships between cumulative occupational radiation dose and specific cancer outcomes in the German aircrew cohort. Methods For a cohort of 26 846 aircrew personnel, standardised mortality ratios (SMR) were calculated. Dose-response analyses were carried out using Poisson regression to assess dose-related cancer risks for the period 1960–2014. Exposure assessment comprises recently available dose register data for all cohort members and newly estimated retrospective cabin crew doses for 1960–2003. Results SMR for all-cause, specific cancer groups and most individual cancers were reduced in all aircrew groups. The only increases were seen for brain cancer in pilots (n=23, SMR 2.01, 95% CI 1.15 to 3.28) and for malignant melanoma (n=10, SMR 1.88, 95% CI 0.78 to 3.85). Breast cancer mortality among female cabin crew was similar to the general population (n=71, SMR 1.06, 95% CI 0.77 to 1.44). Overall median cumulative effective dose was 34.2 mSv (max: 116 mSv) for 1960–2014. No dose-response associations were seen in any of the models. For brain cancer, relative risks were elevated across dose categories. An indicative negative trend with increasing dose category was seen for large intestine cancer in female cabin crew (n=23). Conclusions There was no evidence for significant dose-response patterns for the considered cancer types. Interpretation of results remains difficult as cumulative dose is closely related to age. Future work should focus on investigating radiation jointly with other risk factors that may contribute to risks for specific cancers among aircrew.
This in vivo study reports the influence of minocycline-HCl administration on extra-skeletal bone generation in a Guided Bone Augmentation model, utilizing titanium caps placed on the intact as well as perforated calvaria of rats. The test group was administered 0.5 mg/mL minocycline-HCl with the drinking water, and the amount of bone tissue in the caps was quantified at three time points (4, 8 and 16 weeks). A continuously increased tissue fill was observed in all groups over time. The administration of minocycline-HCl as well as perforation of the calvaria increased this effect, especially with regard to mineralization. The strongest tissue augmentation, with 1.8 times that of the untreated control group, and, at the same time, the most mineralized tissue (2.3× over untreated control), was produced in the combination of both treatments, indicating that systemic administration of minocycline-HCl has an accelerating and enhancing effect on vertical bone augmentation.
Abstract The cellular alterations of the hippocampus lead to memory decline, a shared symptom between Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) patients. However, the subregional deterioration pattern of the hippocampus differs between AD and DLB with the CA1 subfield being more severely affected in AD. The activation of microglia, the brain immune cells, could play a role in its selective volume loss. How subregional microglia populations vary within AD or DLB and across these conditions remains poorly understood. Furthermore, how the nature of the hippocampal local pathological imprint is associated with microglia responses needs to be elucidated. To this purpose, we employed an automated pipeline for analysis of 3D confocal microscopy images to assess CA1, CA3 and DG/CA4 subfields microglia responses in post-mortem hippocampal samples from late-onset AD ( n = 10), DLB ( n = 8) and age-matched control (CTL) ( n = 11) individuals. In parallel, we performed volumetric analyses of hyperphosphorylated tau (pTau), amyloid-β (Aβ) and phosphorylated α-synuclein (pSyn) loads. For each of the 32,447 extracted microglia, 16 morphological features were measured to classify them into seven distinct morphological clusters. Our results show similar alterations of microglial morphological features and clusters in AD and DLB, but with more prominent changes in AD. We identified two distinct microglia clusters enriched in disease conditions and particularly increased in CA1 and DG/CA4 of AD and CA3 of DLB. Our study confirms frequent concomitance of pTau, Aβ and pSyn loads across AD and DLB but reveals a specific subregional pattern for each type of pathology, along with a generally increased severity in AD. Furthermore, pTau and pSyn loads were highly correlated across subregions and conditions. We uncovered tight associations between microglial changes and the subfield pathological imprint. Our findings suggest that combinations and severity of subregional pTau, Aβ and pSyn pathologies transform local microglia phenotypic composition in the hippocampus. The high burdens of pTau and pSyn associated with increased microglial alterations could be a factor in CA1 vulnerability in AD.
