Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable ...effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer.
In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission.
From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 95% CI 6·56–10·02; p<0·0001), being male (1·67 1·19–2·34; p=0·003), and the presence of other comorbidities such as hypertension (1·95 1·36–2·80; p<0·001) and cardiovascular disease (2·32 1·47–3·64). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 0·81–1·72; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks.
Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment.
University of Birmingham, University of Oxford.
Both tissue-specific and ubiquitously expressed transcription factors, such as Sp-family members, are required for correct development. However, the molecular details of how ubiquitous factors are ...involved in programming tissue-specific chromatin and thus participate in developmental processes are still unclear. We previously showed that embryonic stem cells lacking Sp1 DNA-binding activity (Sp1
cells) are able to differentiate into early blood progenitors despite the inability of Sp1 to bind chromatin without its DNA-binding domain. However, gene expression during differentiation becomes progressively deregulated, and terminal differentiation is severely compromised.
Here, we studied the cooperation of Sp1 with its closest paralogue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. The complete absence of either Sp1 or Sp3 or the presence of the Sp1 DNA-binding mutant has only a minor effect on the pattern of distal accessible chromatin sites and their transcription factor binding motif content, suggesting that these mutations do not affect tissue-specific chromatin programming. Sp3 cooperates with Sp1
to enable hematopoiesis, but is unable to do so in the complete absence of Sp1. Using single-cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin binding of Sp1 is required to maintain robust differentiation trajectories.
Our findings highlight the essential contribution of ubiquitous factors such as Sp1 to blood cell development. In contrast to tissue-specific transcription factors which are required to direct specific cell fates, loss of Sp1 leads to a widespread deregulation in timing and coordination of differentiation trajectories during hematopoietic specification.
The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also ...been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.
In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points ...of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.
Stillbirth is a devastating pregnancy outcome that has a profound and lasting impact on women and families. Globally, there are over 2.6 million stillbirths annually and progress in reducing these ...deaths has been slow. Maternal perception of decreased fetal movements (DFM) is strongly associated with stillbirth. However, maternal awareness of DFM and clinical management of women reporting DFM is often suboptimal. The My Baby's Movements trial aims to evaluate an intervention package for maternity services including a mobile phone application for women and clinician education (MBM intervention) in reducing late gestation stillbirth rates.
This is a stepped wedge cluster randomised controlled trial with sequential introduction of the MBM intervention to 8 groups of 3-5 hospitals at four-monthly intervals over 3 years. The target population is women with a singleton pregnancy, without lethal fetal abnormality, attending for antenatal care and clinicians providing maternity care at 26 maternity services in Australia and New Zealand. The primary outcome is stillbirth from 28 weeks' gestation. Secondary outcomes address: a) neonatal morbidity and mortality; b) maternal psychosocial outcomes and health-seeking behaviour; c) health services utilisation; d) women's and clinicians' knowledge of fetal movements; and e) cost. 256,700 births (average of 3170 per hospital) will detect a 30% reduction in stillbirth rates from 3/1000 births to 2/1000 births, assuming a significance level of 5%. Analysis will utilise generalised linear mixed models.
Maternal perception of DFM is a marker of an at-risk pregnancy and commonly precedes a stillbirth. MBM offers a simple, inexpensive resource to reduce the number of stillborn babies, and families suffering the distressing consequences of such a loss. This large pragmatic trial will provide evidence on benefits and potential harms of raising awareness of DFM using a mobile phone app.
ACTRN12614000291684. Registered 19 March 2014.
Protocol Version 6.1, February 2018.
An improved cathode for alkaline fuel cells Bidault, F.; Brett, D.J.L.; Middleton, P.H. ...
International journal of hydrogen energy,
02/2010, Letnik:
35, Številka:
4
Journal Article
Recenzirano
The use of nickel foam as an electrode substrate in alkaline fuel cells (AFCs) has been investigated for bipolar cells incorporating an electrically conducting gas diffusion layer (GDL). Improved ...performance, compared to a previous design, was obtained by adding an extra active layer (AL) composed of manganese (IV) oxide (MnO
2) deposited onto carbon black. This new cathode design performed significantly better (130 mA cm
−2 at 0.8 V and 25 °C) than the previous design (35 mA cm
−2 under the same condition), especially at higher potential. It has been shown that the GDL is a key component of the gas diffusion electrode for both performance and durability, especially with liquid electrolytes. Electrochemical impedance spectroscopy was used to study the various losses in the cathode as a function of electrolyte concentration, oxygen concentration and cell voltage. The typical impedance spectra consisted of one high frequency depressed semi-circle which is believed to be related to porosity and KOH wettability, and one low frequency semi-circle related to electrode kinetics.
Ductal carcinoma in situ (DCIS) is the fourth leading cancer for women in the United States. Understanding of the biology and clinical behavior of DCIS is imperfect. This article highlights the ...current knowledge base and the scientific roadmap needed to advance the field.
This article is based on work done by and consultations obtained from leading experts in the field over a 6-month period that culminated in a full-day symposium designed to systematically review the most pertinent MEDLINE published reports and develop a roadmap to elucidate the molecular steps of carcinogenesis, reduce the extent or prevent the need for therapies, eliminate recurrences, and reduce morbidity.
Expression profiling of pure DCIS will help elucidate the molecular characteristics that distinguish high-risk lesions from clinically irrelevant lesions. The development of new methods of extracting RNA from processed tissues may provide opportunities for research. Mammography often underestimates the pathologic extent of DCIS; other imaging methods need to be investigated for detection and monitoring of disease stability or progression. Novel biologic agents are being delivered in neoadjuvant clinical trials, and alternative methods for breast irradiation are being studied. Future trials of treatment versus no treatment for biologically selected cases of DCIS should be developed.
There is a critical need for a concerted international effort among patients with DCIS, clinicians, and basic scientists to conduct the research necessary to improve fundamental understanding of the biology and clinical behavior of DCIS and prevent development of invasive breast cancer.
Abstract
The emphasis on energy storage has caused renewed interest in alkaline water electrolysis (AWE), where the novel anion exchange membrane (AEM) has opened new pathways to further improve this ...mature technology. The comparison between the novel and the mature is most commonly performed on uneven grounds, as the ionic conductivity of the 30 wt.% (6.89 M) KOH electrolyte used in AWE is significantly greater than the 1.0 M employed in AEM water electrolysis. Through this paper, the performance of a zero-gap water electrolyser is systematically tested utilising either a separator or an AEM in a 1.0 M KOH electrolyte over several temperatures. Catalysed with only untreated nickel foam, the cell configuration with the AEM displayed predictably enough a notably lower series resistance and thereby a lower overpotential. However, the cell with the separator displayed better innate thermal stability, and showed stable results at 25°C, 40°C and 70°C. These findings exhibit the potential of additional R&D efforts in both separators and AEMs.
Chronic kidney disease (CKD) patients have increased risks of sudden cardiac arrest and sudden cardiac death (SCA/SCD) that are not explained by traditional risk factors. We examined associations ...between serum potassium and SCA/SCD in a large cohort of patients with coronary artery disease (CAD) and moderate CKD.
Among 22,009 patients who underwent cardiac catheterization at our institution between 1999 and 2011, 6181 patients had an estimated glomerular filtration rate of ≤60 ml/min per 1.73 m
and were not receiving renal replacement therapy. The risk of SCA/SCD and all-cause mortality associated with potassium concentration was evaluated at the time of cardiac catheterization (baseline) and most proximate to SCA/SCD events. Covariate-adjusted Cox models were used to examine relationships between baseline potassium measurements and outcomes. A propensity score-matched, case-control design was used to assess risk associations of potassium measurements obtained proximate to SCA events.
In the baseline potassium analysis, compared with levels in the normal range, there was no significant risk association between hyperkalemia (>5 mEq/l) or hypokalemia (<3.5 mEq/l) and SCA/SCD or all-cause death after covariate adjustment. In the proximate potassium analysis, hyperkalemia occurred more frequently than hypokalemia (16.7% vs. 3%), and was associated with a doubling in SCA/SCD risk (adjusted odd ratio: 2.37; 95% confidence interval: 1.33-4.23) whereas there was no significant relationship between hypokalemia and outcome.
Among CKD patients with significant CAD, elevated serum potassium levels >5.0 mEq/l are common and are associated with an increased short-term risk of SCA/SCD. Early detection and treatment of hyperkalemia may reduce the high risk of SCD among CKD patients.
The objective of the review is to use individual participant data (IPD) meta‐analysis to explore the effect of mass deworming during pregnancy. We developed a search strategy and searched the ...databases till March 2018. We included individually randomised controlled trials; cluster randomised controlled trials and quasi randomised studies providing preventive or therapeutic deworming drugs for soil transmitted helminthiases and schistosomiasis during pregnancy. All IPD were assessed for completeness, compared to published reports and entered into a common data spreadsheet. Out of the seven trials elgible for IPD, we received data from three trials; out of 8,515 potential IPD participants; data were captured for 5,957 participants. Findings from this IPD suggest that mass deworming during pregnancy reduces maternal anaemia by 23% (Risk ratio RR: 0.77, 95% confidence intreval CI: 0.73–0.81; three trials; 5,216 participants; moderate quality evidence). We did not find any evidence of an effect of mass deworming during pregnancy on any of the other outcomes. There was no evidence of effect modification; however these findings should be interpreted with caution due to small sample sizes. The quality of evidence was rated as moderate for our findings. Our analyses suggest that mass deworming during pregnancy is associated with reducing anaemia with no evidence of impact on any other maternal or pregnancy outcomes. Our analyses were limited by the availability of data for the impact by subgroups and effect modification. There is also a need to support and promote open data for future IPDs.
PDF
