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The number of patients with cancer in Africa has been predicted to increase from 844 279 in 2012 to more than 1·5 million in 2030. However, many countries in Africa still lack access to radiotherapy as a part of comprehensive cancer care. The objective of this analysis is to present an updated overview of radiotherapy resources in Africa and to analyse the gaps and needs of the continent for 2030 in the context of the UN Sustainable Development Goals. Data from 54 African countries on teletherapy megavoltage units and brachytherapy afterloaders were extracted from the Directory for Radiotherapy Centres, an electronic, centralised, and continuously updated database of radiotherapy centres. Cancer incidence and future predictions were taken from the GLOBOCAN 2018 database of the International Agency for Research on Cancer. Radiotherapy need was estimated using a 64% radiotherapy utilisation rate, while assuming a machine throughput of 500 patients per year. As of March, 2020, 28 (52%) of 54 countries had access to external beam radiotherapy, 21 (39%) had brachytherapy capacity, and no country had a capacity that matched the estimated treatment need. Median income was an important predictor of the availability of megavoltage machines: US$1883 (IQR 914–3269) in countries without any machines versus $4485 (3079–12480) in countries with at least one megavoltage machine (p=0·0003). If radiotherapy expansion continues at the rate observed over the past 7 years, it is unlikely that the continent will meet its radiotherapy needs. This access gap might impact the ability to achieve the Sustainable Development Goals, particularly the target to reduce preventable, premature mortality by a third, and meet the target of the cervical cancer elimination strategy of 90% with access to treatment. Urgent, novel initiatives in financing and human capacity building are needed to change the trajectory and provide comprehensive cancer care to patients in Africa in the next decade.

Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. ClinicalTrials.gov NCT01310855.

This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.

This volume based on recent fieldwork by distinguished specialists includes information on the changing economic situation in the countryside, particularly after the ‘owners and tenants’ law of 1992. Along with the effects of structural adjustment on agriculture, marketing, and rural life, several chapters address the declining trend of rural Egyptians to emigrate. Other chapters examine changes in consumption patterns and health, various rural social processes and the ‘new lands’ being reclaimed in Egypt’s desert areas, representations of the rural population in the media and in statistics, and their own changing self-image. What emerges is a picture of a rural Egypt that is full of life, dramatically evolving, and treading a delicate line between progress and impoverishment. Although nothing is typical of rural Egypt, these papers provide a revealing account of the struggles and rewards that characterize the Egyptian countryside today. Contributors: Mohamed Hassan Abdel Aal, Lila Abu-Lughod, Soraya Altorki, Kamran Asdar Ali, Kirsten Haugaard Bach, Ray Bush, Donald Cole, Nicholas Hopkins, François Ireton, Sohair Mehanna, Günter Meyer, Timothy Mitchell, Mohamed M. Mohieddin, Detlef Müller-Mahn, Hans-Christian Korsholm Nielsen, Malak Rouchdy, Reem Saad, Hania Sholkamy, James Toth, Kirsten Westergaard, Peter Winch, Ahmed Zayed.

There is a high rate of isocitrate dehydrogenase (IDH) 1 and 2 mutations in low grade gliomas and in high grade gliomas derived from them. IDH analysis of gliomas is a novel adjunct to traditional classification and an independent prognostic marker. We compared antibody and sequencing methods for the detection of IDH mutations. 88 samples from 74 patients were identified: 16 patients had WHO grade II gliomas, 30 had WHO grade III gliomas, and 28 had WHO grade IV glioblastoma multiforme (GBM). 31 samples had insufficient material available for DNA extraction. For immunohistochemistry, sections were stained with anti-IDH1R132H antibody. For sequencing, DNA was extracted from fresh, frozen tissue. 20 (28%) of 72 patients were positive for the R132H IDH1 mutation by antibody. An IDH1 mutation was detected by molecular genetics in 21 (37%) of 57 patients, and no IDH2 mutations were detected (6% expected from previous studies). 5 (24%) of 21 patients had rare IDH1 mutations not detected by immunohistochemistry (7% expected). Three of these patients displayed the p.Arg132Cys mutation (two anaplastic astrocytomas, one fibrillary astrocytoma) and two displayed p.Arg132Gly (one anaplastic astrocytoma, one anaplastic oligoastrocytoma). Where sufficient tissue was available, immunohistochemistry and DNA analysis were fully concordant for the p.Arg132His mutation. We found a high rate of IDH1 mutations in lower grade lesions (WHO grade II and III) (54% [25/46]) and a low rate in GBMs (7% [2/28]). Both grade II gliomas and anaplastic astrocytomas showed a statistically different distribution of IDH1 mutation load compared with GBMs (p<0·0001 and p=0·0021, respectively). A rationalised combined approach involving R132H antibody testing and sequencing of negative cases would be ideal for the detection of IDH1 mutations. Antibody testing is cheaper than sequencing but sequencing demonstrates rare IDH1 mutations not detected by immunohistochemistry. Brain Tumour Bank Frenchay, British Neuropathological Society, and Brain Tumour Action.

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and in some cases also other tumor types, with moderate to very high frequencies. Surprisingly, 11 of the 12 lines were each heterozygous for a mutation in a different ribosomal protein (RP) gene, while one line was heterozygous for a mutation in a zebrafish paralog of the human and mouse tumor suppressor gene, neurofibromatosis type 2. Our findings suggest that many RP genes may act as haploinsufficient tumor suppressors in fish. Many RP genes might also be cancer genes in humans, where their role in tumorigenesis could easily have escaped detection up to now.

Radiofrequency endometrial ablation (REA) is currently a second line treatment in women with heavy menstrual bleeding (MHB) if medical therapy (MTP) is contraindicated or unsatisfactory. Our objective is to compare the effectiveness and cost burden of MTP and REA in the initial treatment of HMB. We performed a randomized trial at Mayo Clinic Rochester, Minnesota. The planned sample size was 60 patients per arm. A total of 67 women with HMB were randomly allocated to receive oral contraceptive pills (Nordette ®) or Naproxen (Naprosyn®) (n = 33) or REA (n = 34). Primary 12-month outcome measures included menstrual blood loss using pictorial blood loss assessment chart (PBLAC), patients' satisfaction, and Menorrhagia Multi-Attribute Scale (MMAS). Secondary outcomes were total costs including direct medical and indirect costs associated with healthcare use, patient out-of-pocket costs, and lost work days and activity limitations over 12 months. Compared to MTP arm, women who received REA had a significantly lower PBLAC score (median [Interquartile range, IQR]: 0 [0-4] vs. 15 [0-131], p = 0.003), higher satisfaction rates (96.8%vs.63.2%, p = 0.003) and higher MMAS (median [IQR]: 100 [100-100] vs. 100 [87-100], p = 0.12) at 12 months. Direct medical costs were higher for REA ($5,331vs.$2,901, 95% confidence interval (CI) of mean difference:$727,$4,852), however, when indirect costs are included, the difference did not reach statistical significance ($5,469 vs. $3,869, 95% CI of mean difference:-$339, $4,089). For women with heavy menstrual bleeding, initial radiofrequency endometrial ablation compared to medical therapy offered superior reduction in menstrual blood loss and improvement in quality of life without significant differences in total costs of care. NCT01165307.

Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human clinical isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males than in females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 10 5 50% tissue culture infective dose (TCID 50 ) of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developed more extensive pneumonia as noted on chest computed tomography, and recovered more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including interferon-β (IFN-β) and tumor necrosis factor-α (TNF-α), were comparable between the sexes. However, during the recovery phase of infection, females mounted 2-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole-inactivated SARS-CoV-2 and mutant S-RBDs as well as virus-neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2-associated sex differences seen in the human population. IMPORTANCE Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After inoculation, male hamsters experienced greater sickness, developed more severe lung pathology, and recovered more slowly than females. Sex differences in disease could not be reversed by estradiol treatment in males and were not explained by either virus replication kinetics or the concentrations of inflammatory cytokines in the lungs. During the recovery period, antiviral antibody responses in the respiratory tract and plasma, including to newly emerging SARS-CoV-2 variants, were greater in female than in male hamsters. Greater lung pathology during the acute phase combined with lower antiviral antibody responses during the recovery phase of infection in males than in females illustrate the utility of golden Syrian hamsters as a model to explore sex differences in the pathogenesis of SARS-CoV-2 and vaccine-induced immunity and protection.

Background Post-operative pulmonary complications (PPCs) are an important source of morbidity and mortality after major abdominal and thoracic surgery. The use of neuromuscular blocking drugs in general anaesthesia is an important risk factor for PPCs. The incomplete reversal of this neuromuscular blockade at the end of surgery leads to residual weakness of respiratory muscles and predisposes to aspiration of pharyngeal contents, hypoventilation, and thus to PPCs such as atelectasis and pneumonia. Two reversal drugs for neuromuscular blocking agents are available: neostigmine and sugammadex. Compared with neostigmine, sugammadex use results in more rapid reversal of neuromuscular blockade, and small clinical efficacy studies have suggested an associated lower incidence of PPCs. The comparative clinical effectiveness of the two drugs in reducing length of hospital stay or mortality is uncertain. Moreover, a potential safety concern with sugammadex is the relatively high incidence of life-threatening allergic reactions in countries where this drug has been widely used over the last decade. Methods SINFONIA is a pragmatic, randomised, open-label, parallel group, superiority trial with an internal pilot which aims to compare the clinical and cost effectiveness of the two available drugs for reversal of neuromuscular blockade, sugammadex and neostigmine, in patients aged 50 years or older undergoing major abdominal or non-cardiac thoracic surgery. The trial will randomise 2500 patients from approximately 40 centres in the UK. The primary outcome will be days alive and out of hospital at 30 days (DAH-30), with key secondary outcomes of PPC incidence, quality of life, and mortality up to 180 days. An embedded observational study will investigate the rate of allergic sensitisation following exposure to sugammadex. Discussion The SINFONIA trial addresses an important question for anaesthetists and for patients undergoing major abdominal and thoracic surgery. The choice of reversal agent for neuromuscular blockade between sugammadex and neostigmine is currently largely a matter of anaesthetist preference. A growing body of evidence suggests that sugammadex may reduce the incidence of post-operative pulmonary complications relative to neostigmine. This pragmatic clinical effectiveness trial will provide robust evidence as to the effects of the two drugs on patient-centred outcomes such as DAH-30, as well as on cost effectiveness and the incidence of allergic sensitisation. Trial registration The trial was registered on the ISRCTN database ( https://www.isrctn.com ) prior to opening to recruitment (registration no 15109717).

IntroductionNatural experiments are considered a priority for examining causal associations between the built environment (BE) and physical activity (PA) because the randomised controlled trial design is rarely feasible. Few natural experiments have examined the effects of walking and cycling infrastructure on PA and active transport in adults, and none have examined the effects of such changes on PA and active transport to school among adolescents. We conducted the Built Environment and Active Transport to School (BEATS) Study in Dunedin city, New Zealand, in 2014–2017. Since 2014, on-road and off-road cycling infrastructure construction has occurred in some Dunedin neighbourhoods, including the neighbourhoods of 6 out of 12 secondary schools. Pedestrian-related infrastructure changes began in 2018. As an extension of the BEATS Study, the BEATS Natural Experiment (BEATS-NE) (2019–2022) will examine the effects of BE changes on adolescents’ active transport to school in Dunedin, New Zealand.Methods and analysisThe BEATS-NE Study will employ contemporary ecological models for active transport that account for individual, social, environmental and policy factors. The published BEATS Study methodology (surveys, accelerometers, mapping, Geographic Information Science analysis and focus groups) and novel methods (environmental scan of school neighbourhoods and participatory mapping) will be used. A core component continues to be the community-based participatory approach with the sustained involvement of key stakeholders to generate locally relevant data, and facilitate knowledge translation into evidence-based policy and planning.Ethics and disseminationThe BEATS-NE Study has been approved by the University of Otago Ethics Committee (reference: 17/188). The results will be disseminated through scientific publications and symposia, and reports and presentations to stakeholders.Trial registration numberACTRN12619001335189.