Coverage survey and lessons learned from a pre-emptive cholera vaccination campaign in urban and rural communities affected by landslides and floods in Freetown Sierra Leone.

BACKGROUND: On 14 August 2017, massive landslides and floods hit Freetown (Sierra Leone). More than 1,000 people lost their lives while approximately 6,000 people were displaced. The areas most affected included parts of the town with challenged access to basic water and sanitation facilities, with communal water sources likely contaminated by the disaster. To avert a possible cholera outbreak following this emergency, the Ministry of Health and Sanitation (MoHS), supported by the World Health Organization (WHO) and international partners, including Médecins Sans Frontières (MSF) and UNICEF, launched a two-dose pre-emptive vaccination campaign using Euvichol™, an oral cholera vaccine (OCV). METHODS: We conducted a stratified cluster survey to estimate vaccination coverage during the OCV campaign and also monitor adverse events. The study population - subsequently stratified by age group and residence area type (urban/rural) - included all individuals aged 1 year or older, living in one of the 25 communities targeted for vaccination. RESULTS: In total 3,115 households were visited, 7,189 individuals interviewed; 2,822 (39%) people in rural and 4,367 (61%) in urban areas. The two-dose vaccination coverage was 56% (95% confidence interval (CI): 51.0-61.5), 44% (95%CI: 35.2-53.0) in rural and 57% (95%CI: 51.6-62.8) in urban areas. Vaccination coverage with at least one dose was 82% (95%CI: 77.3-85.5), 61% (95%CI: 52.0-70.2) in rural and 83% (95%CI: 78.5-87.1) in urban areas. CONCLUSIONS: The Freetown OCV campaign exemplified a timely public health intervention to prevent a cholera outbreak, even if coverage was lower than expected. We hypothesised that vaccination coverage in Freetown was sufficient in providing at least short-term immunity to the population. However, long-term interventions to ensure access to safe water and sanitation are needed.

Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery.

Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS. SIGNIFICANCE: Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision.

Multicellular Systems to Translate Somatic Cell Genome Editors to Humans.

As genome editors move into clinical trials, there is a need to establish ex vivo multicellular systems to rapidly assess and predict toxic effects of genome editors in physiologically relevant human models. Advancements in organoid and organs-on-chip technologies offer the possibility to create multicellular systems that replicate the cellular composition and metabolic function of native tissues. Some multicellular systems have been validated in multiple applications for drug discovery and could be easily adapted to test genome editors; other models, especially those of the adaptive immune system, will require validation before being used as benchmarks for testing genome editors. Likewise, protocols to assess immunogenicity, to detect off-target effects, and to predict ex vivo to in vivo translation will need to be established and validated. This review will discuss key aspects to consider when designing, building, and/or adopting in vitro human multicellular systems for testing genome editors.

Medial frontal theta dissociates unsuccessful from successful avoidance and is modulated by lack of perseverance.

Medial frontal activity in the EEG is enhanced following negative feedback and varies in relation to dimensions of impulsivity. In 22 undergraduate students (Mage = 18.92 years, range 18-22 years), we employed a probabilistic negative reinforcement learning paradigm in which choices to avoid were followed by cues indicating successful or unsuccessful avoidance of an impending aversive noise. Our results showed that medial frontal theta power was enhanced following a cue that signaled avoidance was unsuccessful. In addition, self-reported lack of perseverance, a dimension of impulsivity characterized by an inability to maintain focus and determination during a challenging task, was negatively correlated with medial frontal theta elicited to an unsuccessful avoidance cue. We also observed robust differences in alpha attenuation and beta modulation following unsuccessful avoidance cue presentation. To our knowledge, this is the first study in humans to show a functional relation between medial frontal theta modulation and avoidance success. We discuss our findings in the context of frontal theta and self-regulation, negative reinforcement, and anxiety.