Methodological issues in quantifying the magnitude of the tuberculosis problem in a prison population

SETTING: Correctional settings and remand prisons. OBJECTIVE: To critically discuss calculations for epidemiological indicators of the tuberculosis (TB) burden in prisons and to provide recommendations to improve study comparability. METHODS: A hypothetical data set illustrates issues in determining incidence and prevalence. The appropriate calculation of the incidence rate is presented and problems arising from cross-sectional surveys are clarifi ed. RESULTS: Cases recognized during the fi rst 3 months should be classifi ed as prevalent at entry and excluded from any incidence rate calculation. The numerator for the incidence rate includes persons detected as having developed TB during a specifi ed period of time subsequent to the initial 3 months. The denominator is persontime at risk from 3 months onward to the end point (TB or end of the observation period). Preferably, entry time, exit time and event time are known for each inmate to determine person-time at risk. Failing that, an approximation consists of the sum of monthly head counts, excluding prevalent cases and those persons no longer at risk from both the numerator and the denominator. CONCLUSIONS: The varying durations of inmate incarceration in prisons pose challenges for quantifying the magnitude of the TB problem in the inmate population. Recommendations are made to measure incidence and prevalence.

Emergency department admissions to a prison hospital: a retrospective cohort study from Switzerland

There are more than 10 million prison inmates throughout the world and this number is increasing continuously. Prisoners are a particularly vulnerable minority group that has special healthcare needs and demands on healthcare services and providers. The aim of this study was to give an overview of prisoners' healthcare problems leading to emergency department admission, in order to make recommendations to help to optimise treatment of this target group.

Break detection of annual Swiss temperature series

[1] Instrumental temperature series are often affected by artificial breaks (“break points”) due to (e.g.,) changes in station location, land-use, or instrumentation. The Swiss climate observation network offers a high number and density of stations, many long and relatively complete daily to sub-daily temperature series, and well-documented station histories (i.e., metadata). However, for many climate observation networks outside of Switzerland, detailed station histories are missing, incomplete, or inaccessible. To correct these records, the use of reliable statistical break detection methods is necessary. Here, we apply three statistical break detection methods to high-quality Swiss temperature series and use the available metadata to assess the methods. Due to the complex terrain in Switzerland, we are able to assess these methods under specific local conditions such as the Foehn or crest situations. We find that the temperature series of all stations are affected by artificial breaks (average = 1 break point / 48 years) with discrepancies in the abilities of the methods to detect breaks. However, by combining the three statistical methods, almost all of the detected break points are confirmed by metadata. In most cases, these break points are ascribed to a combination of factors in the station history.

Are full or empty beer bottles sturdier and does their fracture-threshold suffice to break the human skull?

Beer bottles are often used in physical disputes. If the bottles break, they may give rise to sharp trauma. However, if the bottles remain intact, they may cause blunt injuries. In order to investigate whether full or empty standard half-litre beer bottles are sturdier and if the necessary breaking energy surpasses the minimum fracture-threshold of the human skull, we tested the fracture properties of such beer bottles in a drop-tower. Full bottles broke at 30 J impact energy, empty bottles at 40 J. These breaking energies surpass the minimum fracture-threshold of the human neurocranium. Beer bottles may therefore fracture the human skull and therefore serve as dangerous instruments in a physical dispute.

Global, regional, and local measures of complexity of multichannel electroencephalography in acute, neuroleptic-naive, first-break schizophrenics

Background: Schizophrenic symptoms commonly are felt to indicate a loosened coordination, i.e. a decreased connectivity of brain processes. Methods: To address this hypothesis directly, global and regional multichannel electroencephalographic (EEG) complexities (omega complexity and dimensional complexity) and single channel EEG dimensional complexities were calculated from 19-channel EEG data from 9 neuroleptic-naive, first-break, acute schizophrenics and 9 age- and sex-matched controls. Twenty artifact-free 2 second EEG epochs during resting with closed eyes were analyzed (2–30 Hz bandpass, average reference for global and regional complexities, local EEG gradient time series for single channels). Results: Anterior regional Omega-Complexity was significantly increased in schizophrenics compared with controls (p < 0.001) and anterior regional Dimensional Complexity showed a trend for increase. Single channel Dimensional Complexity of local gradient waveshapes was prominently increased in the schizophrenics at the right precentral location (p = 0.003). Conclusions: The results indicate a loosened cooperativity or coordination (vice versa: an increased independence) of the active brain processes in the anterior brain regions of the schizophrenics.

Time for a break: admissions to an urban emergency department after working out-a retrospective study from Switzerland.

Background. The present retrospective study was intended to investigate whether working out and other low-speed sports can provoke cardiovascular, neurological, or traumatic damage. Material and Methods. Patient data from 2007 to 2013 was collected and saved at the university department of emergency medicine in an electronic patient record database. Results. Of the 138 patients included in this study, 83.3% (n = 115) were male and 16.7% female (n = 23). Most admissions were due to musculoskeletal accidents (n = 77; 55.8%), followed by neurological incidents (n = 23; 16.7%), cardiovascular incidents (n = 19; 13.8%), soft tissue injuries (n = 3; 2.2%), and others (n = 16; 11.6%). The mean age of the allover injured people was 36.7 years. The majority of the patients (n = 113; 81.9%) were treated as outpatients; 24 (17.4%) were inpatients. Discussion. In Switzerland, this is the first study that describes emergency department admissions after workout and examines trauma and neurological and cardiovascular incidents. As specific injuries, such as brain haemorrhages, STEMIs, and epileptic seizures, were relatively frequent, it was hypothesised that workout with its physiological changes may be an actual trigger for these injuries, at least for a specific population. Conclusion. Strenuous physical activity may trigger the risk of cardiovascular, neurological, or trauma events.

The Drosophila chk2 gene loki is essential for embryonic DNA double-strand-break checkpoints induced in S phase or G2

Cell cycle checkpoints are signal transduction pathways that control the order and timing of cell cycle transitions, ensuring that critical events are completed before the occurrence of the next cell cycle transition. The Chk2 family of kinases is known to play a central role in mediating the cellular responses to DNA damage or DNA replication blocks in various organisms. Here we show through a phylogenetic study that the Drosophila melanogaster serine/threonine kinase Loki is the homolog of the yeast Mek1p, Rad53p, Dun1p, and Cds1 proteins as well as the human Chk2. Functional analyses allowed us to conclude that, in flies, chk2 is involved in monitoring double-strand breaks (DSBs) caused by irradiation during S and G2 phases. In this process it plays an essential role in inducing a cell cycle arrest in embryonic cells. Our results also show that, in contrast to C. elegans chk2, Drosophila chk2 is not essential for normal meiosis and recombination, and it also appears to be dispensable for the MMS-induced DNA damage checkpoint and the HU-induced DNA replication checkpoint during larval development. In addition, Drosophila chk2 does not act at the same cell cycle phases as its yeast homologs, but seems rather to be involved in a pathway similar to the mammalian one, which involves signaling through the ATM/Chk2 pathway in response to genotoxic insults. As mutations in human chk2 were linked to several cancers, these similarities point to the usefulness of the Drosophila model system.

REV7 counteracts DNA double-strand break resection and affects PARP inhibition

Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.