It is impossible to be certain, but it is estimated that each year in England and Wales there may be about 30–40 infant deaths from covert homicide, which represents about 10% of the current annual ...total of sudden unexpected deaths in infancy. This paper reviews the features that have been suggested as possible indicators of covert homicide, describes the difficulties in its identification and the need for better evidence, and emphasises the importance of thorough medical investigation of all sudden infant deaths.
The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- ...mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eμ-Myc lymphoma cells but, counterintuitively, c-rel-/- Eμ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel-/- Eμ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eμ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel-/- TCL1-Tg mice and RelA Thr505Ala mutant Eμ-Myc mice. Analysis of wild-type Eμ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel-/- mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-κB/IκB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-κB signalling in cancer.
Aims
The objectives of this work were to characterize molecularly the morphologically described endophyte Balansia epichloe symbiotic on three grass species, and to determine the in situ production ...of ergot alkaloids on these three symbiota.
Methods and Results
Balansia epichloe symbiotic with smut grass (Sporobolus poiretii), love grass (Eragrostis hirsuta) and lace grass (Eragrostis capillaries, a new host) were characterized using DNA barcoding. Laser ablation electro spray ionization (LAESI)–mass spectrometry was used to detect ergot alkaloids in situ for each symbiotum.
Conclusions
The three morphologically described symbionts on the three host grasses were indicated as belonging to the species B. epichloe, DNA barcoding suggested they were related although a cryptic species was suggested. LAESI–mass spectrometry showed that ergot alkaloids were produced in vivo in two hosts but not the third although this same symbiotum was related to one of the ergot alkaloid producing symbiota as revealed by the DNA‐barcoding procedure.
Significance and Impact of the Study
These results established the accumulation of ergot alkaloids in pot culture by a morpho species although there were variations with each species of grass. Barcoding described divergence among species, but considering its limitation, the suggested existence of cryptic species among this morphospecies requires substantiation by studies that are more rigorous.
An experimental method is developed to perform Hopkinson tests by means of viscoelastic bars by considering the wave propagation attenuation and dispersion due to the material rheological properties ...and the bar radial inertia (geometric effect). A propagation coefficient, representative of the wave dispersion and attenuation, is evaluated experimentally. Thus, the Pochhammer and Chree frequency equation is not necessary. Any bar cross-section shapes can be employed, and the knowledge of the bar mechanical properties is useless. The propagation coefficients for two PMMA bars with different diameters and for an elastic aluminum alloy bar are evaluated. These coefficients are used to determine the normal forces at the free end of a bar and at the ends of two bars held in contact. As an application, the mechanical impedance of an accelerometer is evaluated.
Introduction
Optimizing HIV prevention may require structured approaches for providing client‐centred choices as well as community‐based entry points and delivery. We evaluated the effect of a ...dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa.
Methods
We conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client‐centred HIV prevention model, including (1) structured client choice of product (pre‐exposure prophylaxis PrEP or post‐exposure prophylaxis PEP), service location (clinic or out‐of‐clinic) and HIV testing modality (self‐test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48‐week follow‐up with self‐reported PrEP or PEP use.
Results
From May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15–24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow‐up; self‐testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out‐of‐facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0–31.9%, p<0.001). Impact was larger during periods of self‐reported HIV risk: 36.6% coverage in intervention versus 0.9% in control, a difference of 35.7% (95% CI: 27.5–43.9, p<0.001). Intervention effects were seen across subgroups defined by sex, age group and alcohol use.
Conclusions
A client‐centred dynamic choice HIV prevention intervention, including the option to switch between products and CHW‐based delivery in the community, increased biomedical prevention coverage by 27.5%. However, substantial person‐time at risk of HIV remained uncovered.
Dysfunctional breathing is characterised by an abnormal breathing pattern leading to respiratory symptoms. The 25-item Self Evaluation of Breathing Questionnaire (SEBQ) has been developed to measure ...breathing-related symptoms and their severity but lacks thorough evaluation. To determine reproducibility, internal consistency and predictors of SEBQ score, 180 participants completed an online SEBQ with additional demographic and lifestyle questions. Two weeks later, 155 of those repeated SEBQ. Test–retest correlation of the SEBQ was high intraclass correlation coefficient (3, 1) = 0.89; 95 % CI 0.85–0.92. There was no difference in SEBQ score between test and retest (15.1 (11.6) mean (SD) versus 14.7 (12.4);
P
= 0.4) and the score showed a typical error (standard error of measurement) of 4.0. Internal consistency was high (Cronbach’s α = 0.93), and a single factor structure for items was shown. Smoking status, reported respiratory disease, recent respiratory illness and female gender were positively-associated predictors of SEBQ score, and together explained 25.6 % of score variance (
P
≤ 0.001). The SEBQ has high test–retest reproducibility and its score may be predicted by current smoking, chronic respiratory disease, recent respiratory illness and female gender, thus may be a useful clinical screening tool for dysfunctional breathing.
Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising ...radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.
Guided torsional waves in a bar with a noncircular cross section have been exploited by previous researchers to measure the density of fluids. However, due to the complexity of the wave behavior in ...the noncircular cross-sectional shape, the previous theory can only provide an approximate prediction; thus the accuracy of the measurement has been compromised. In this paper, a semianalytical finite element method is developed to model accurately the propagation velocity and leakage of guided waves along an immersed waveguide with arbitrary noncircular cross section. An accurate inverse model is then provided to measure the density of the fluid by measuring the change of the torsional wave speed. Experimental results obtained with a rectangular bar in a range of fluids show very good agreement with the theoretical predictions. Finally, the potentials to use the model for sensor optimization are discussed.