Minimizing verification bias in cervical cancer screening of HIV-infected women

Approximately one-third of cervical intraepithelial neoplasia 2 and above can be missed by only biopsying quadrants of the cervix with visible lesions by digital cervicography

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

A comprehensive assessment of breast and cervical cancer control infrastructure in Zambia

Introduction: By 2030 cancer will kill one million Africans each year. Women will bear the heaviest burden, as cancers of the breast and cervix are the most common malignancies and causes of cancer-related death in the African region. National-level data that map the status of women's cancer control services are needed to inform strategies for implementing platforms for the early detection and treatment of these “priority” cancers. Methods: Using mixed-methods, we assessed available services for breast and cervical cancer detection and treatment at all provincial hospitals, the national referral hospital, and the national cancer treatment center in Zambia. Results: A system for cervical cancer prevention using visual inspection with acetic acid (VIA) and ablation/excision of precancerous lesions has been established at the provincial level. The potential for mammography, clinical breast examination, diagnostic ultrasound and biopsy exist at the provincial level, albeit on a much smaller scale. Breast wedge resections and mastectomy can be performed in provinces where general surgeons are located; however, breast conserving and reconstructive surgery are not available. Invasive cancers are generally referred to University Teaching Hospital in Lusaka, where services for radiation, chemotherapy and hormonal therapy are available but overburdened. Pathology services nationwide are woefully inadequate. Discussion: The assessment revealed a critical need for centrally coordinated, but decentralized, public service platforms for women's cancer control. Efforts are underway, through multiple stakeholders, to implement recommendations related to training healthcare workers who can provide advanced diagnostic and therapeutic services, improving pathology services, and innovative financing for these initiatives

Diagnosis and management of Guillain-Barré syndrome in ten steps

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae

β-delayed particle decay of 9C and the A = 9, T = 1/2 nuclear system: Experiment, data, and phenomenological analysis

The β decay of 9C (T1/2 = 126.5 ms) has been studied in two experiments observing about 15 × 107 and 8 × 107 decays, respectively, at the TISOL facility at TRIUMF; different detector configurations were employed in the two experiments. In this first of two papers, the two experimental setups are described, as well as data analysis and a phenomenological approach to deducing branching ratios to and from states in 9B. In the experiments single spectra, and double and triple coincidence spectra, were recorded. Several states in 9B were observed; β-branching ratios to these states, and particle decay channels from these states, are reported. In particular, secondary decays into the 5Li and 8Be ground states were observed. With the inclusion of a considerable continuum and additional states, fair agreement with the reported 9Li logft values is found with a phenomenological approach for deducing the branching ratios. To extend the discussion, in a second, forthcoming paper, a multichannel, multistate R-matrix analysis of these data will be described

Breast cancer in patients with germline TP53 pathogenic variants have typical tumour characteristics: the Cohort study of TP53 carrier early onset breast cancer (COPE study)

Germline TP53 pathogenic variants are rare but associated with a high risk of cancer; they are often identified in the context of clinically diagnosed Li-Fraumeni syndrome predisposing to a range of young onset cancers including sarcomas and breast cancer. The study aim was to conduct a detailed morphological review and immuno-phenotyping of breast cancer arising in carriers of a germline TP53 pathogenic variant. We compared breast cancers from five defined groups: (1) TP53 carriers with breast cancer (n = 59), (2) early onset HER2-amplified breast cancer, no germline pathogenic variant in BRCA1/2 or TP53 (n = 55), (3) BRCA1 pathogenic variant carriers (n = 60); (4) BRCA2 pathogenic variant carriers (n = 61) and (5) young onset breast cancer with no known germline pathogenic variant (n = 98). Pathologists assessed a pre-agreed set of morphological characteristics using light microscopy. Immunohistochemistry (IHC) for HER2, ER, PR, p53, integrin alpha v beta 6 (αvβ6) integrin, α-smooth muscle actin (α-SMA) and pSMAD2/3 was performed on tissue microarrays of invasive carcinoma. We confirmed a previously reported high prevalence of HER2-amplified, ductal no special type invasive breast carcinoma amongst known TP53 germline pathogenic variant carriers 20 of 36 (56%). Furthermore we observed a high frequency of densely sclerotic tumour stroma in cancers from TP53 carriers (29/36, 80.6%) when compared with non-carriers, 50.9% (28/55), 34.7% (50/144), 41.4% (65/157), 43.8% (95/217) in groups 2-5 respectively. The majority of germline TP53 gene carrier breast tumours had a high intensity of integrin αvβ6, α-SMA and pSMAD2/3 expression in the majority of cancer cells. In conclusion, aggressive HER2 positive breast cancers with densely sclerotic stroma are common in germline TP53 carriers. High levels of αvβ6 integrin, α-SMA and pSMAD2/3 expression suggest that the dense stromal phenotype may be driven by upregulated transforming growth factor beta signalling.Kate Packwood, Guy Martland, Matthew Sommerlad, Emily Shaw, Karwan Moutasim ... Nicola Poplawski ... et al

β-delayed particle decay of 17ne into p + α + 12C through the isobaric analog state in 17F

We have observed the breakup of the isobaric analog state at 11.193 MeV in 17F into three particles via three channels: proton decay to the α-unbound 9.585 MeV state in 16O; and α decay to the proton-unbound 2.365 and 3.502/3.547 MeV states in 13N. Laboratory α-particle spectra corresponding to these three modes have been generated in Monte Carlo simulations using single-channel, single- and multilevel R-matrix formulas. A fit of these spectra to the α spectrum resulting from a triple-coincidence measurement results in excellent agreement with the experimental spectrum and allows branching ratios to be deduced for these rare decay modes

Three-particle breakup of the isobaric analog state in 17F

We have studied the b-delayed particle decay of 17Ne to test the feasibility of determining both the E1 and E2 components of the 12C(a,g )16O cross section at energies relevant to helium burning in stars. In this context we have observed the breakup of the isobaric analog state in 17F at 11.193 MeV into three particles via three channels: proton decay to the 9.59 MeV state in 16O; and a decay to the 2.365 and 3.502/3.547 MeV states in 13N. This is the first reported observation of the decay of the IAS to the 12 state in 16O at 9.59 MeV and the first reported b-delayed proton-a decay. With straightforward improvements to our detection apparatus to improve angular resolution, b suppression, and solid angle coverage, we should be able to proceed to the measurement of the effect of the tail of the subthreshold state at 7.117 MeV in 16O on thea spectrum from the breakup of the 9.59 MeV state