Recent Decisions

Comments on recent decisions by Thomas D. Ready, Martin F. Idzik, James E. Hakes, Stephen A. Seall, and Michael J. Schimberg

Evolution of vertebrate retinal photoreception

Recent findings shed light on the steps underlying the evolution of vertebrate photoreceptors and retina. Vertebrate ciliary photoreceptors are not as wholly distinct from invertebrate rhabdomeric photoreceptors as is sometimes thought. Recent information on the phylogenies of ciliary and rhabdomeric opsins has helped in constructing the likely routes followed during evolution. Clues to the factors that led the early vertebrate retina to become invaginated can be obtained by combining recent knowledge about the origin of the pathway for dark re-isomerization of retinoids with knowledge of the inability of ciliary opsins to undergo photoreversal, along with consideration of the constraints imposed under the very low light levels in the deep ocean. Investigation of the origin of cell classes in the vertebrate retina provides support for the notion that cones, rods and bipolar cells all originated from a primordial ciliary photoreceptor, whereas ganglion cells, amacrine cells and horizontal cells all originated from rhabdomeric photoreceptors. Knowledge of the molecular differences between cones and rods, together with knowledge of the scotopic signalling pathway, provides an understanding of the evolution of rods and of the rods' retinal circuitry. Accordingly, it has been possible to propose a plausible scenario for the sequence of evolutionary steps that led to the emergence of vertebrate photoreceptors and retina

Avalanche of Bifurcations and Hysteresis in a Model of Cellular Differentiation

Cellular differentiation in a developping organism is studied via a discrete bistable reaction-diffusion model. A system of undifferentiated cells is allowed to receive an inductive signal emenating from its environment. Depending on the form of the nonlinear reaction kinetics, this signal can trigger a series of bifurcations in the system. Differentiation starts at the surface where the signal is received, and cells change type up to a given distance, or under other conditions, the differentiation process propagates through the whole domain. When the signal diminishes hysteresis is observed

The detection, survival and persistence of Staphylococcus capitis NRCS-A in neonatal units in England

BACKGROUND: The multi-drug resistant Staphylococcus capitis clone, NRCS-A is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonise surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonisations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whilst S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for 3 days with minimal losses in viability (< 0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment

Changes in dental plaque following hospitalisation in a critical care unit: an observational study

Additional funding was provided by a grant from the Faculty of Dental Surgery, Royal College of Surgeons, England, and this work was undertaken at University College London/University College London Hospitals, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme

Third-Line Nivolumab Monotherapy in Recurrent Small Cell Lung Cancer : CheckMate 032

Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC. Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5\u201319.5) with a median duration of response of 17.9 months (range 3.0\u201342.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events. Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population

Environmental Influences on Fish Species Distribution in the Musolo River System, Congo River Basin (Democratic Republic of the Congo, Central Africa)

Ichthyofaunal distribution was studied in the Musolo River system, a small affluent tributary of the Congo River flowing into Pool Malebo (Democratic Republic of the Congo). Twelve ecological stations were sampled, of which eight were located in the Musolo main-channel and four in the Fushi River, a principal tributary of the Musolo. Each station was sampled four times over a two-year period, with fishing techniques following standardized methods utilizing dip and cast nets, and nine environment variables were measured at each station. Fifty-three fish species belonging to 36 genera and 16 families were collected with the Alestidae, Distichodontidae, Cichlidae, Cyprinidae, Mormyridae, and Mochokidae being the most diversified. Redundancy Analysis with forward selection coupled with Monte Carlo permutation tests (499 permutations) identified total dissolved solid (25.8%) and altitude (24.4%) as accounting for 50.2% of total variance (p &lt; 0.05). The contribution of the two first axes was significant (F = 3.41; p = 0.004). Species richness increases from upstream to downstream. In general, the high value of Shannon’s diversity (1.07-2.67) and Equitability European Scientific Journal November 2019 edition Vol.15, No.33 ISSN: 1857 – 7881 (Print) e - ISSN 1857- 7431 193 (0.62-0.96) indices at all sites, indicates that the examined stretch of the Musolo River system is in good ecological health, despite its location adjacent to the megacity of Kinshasa

Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection