Islands beneath islands: phylogeography of a groundwater amphipod crustacean in the Balearic archipelago

<p>Abstract</p> <p>Background</p> <p>Metacrangonyctidae (Amphipoda, Crustacea) is an enigmatic continental subterranean water family of marine origin (thalassoid). One of the species in the genus, <it>Metacrangonyx longipes</it>, is endemic to the Balearic islands of Mallorca and Menorca (W Mediterranean). It has been suggested that the origin and distribution of thalassoid crustaceans could be explained by one of two alternative hypotheses: (1) active colonization of inland freshwater aquifers by a marine ancestor, followed by an adaptative shift; or (2) passive colonization by stranding of ancestral marine populations in coastal aquifers during marine regressions. A comparison of phylogenies, phylogeographic patterns and age estimations of clades should discriminate in favour of one of these two proposals.</p> <p>Results</p> <p>Phylogenetic relationships within <it>M. longipes </it>based on three mitochondrial DNA (mtDNA) and one nuclear marker revealed five genetically divergent and geographically structured clades. Analyses of cytochrome oxidase subunit 1 (<it>cox1</it>) mtDNA data showed the occurrence of a high geographic population subdivision in both islands, with current gene flow occurring exclusively between sites located in close proximity. Molecular-clock estimations dated the origin of <it>M. longipes </it>previous to about 6 Ma, whereas major cladogenetic events within the species took place between 4.2 and 2.0 Ma.</p> <p>Conclusions</p> <p><it>M. longipes </it>displayed a surprisingly old and highly fragmented population structure, with major episodes of cladogenesis within the species roughly correlating with some of the major marine transgression-regression episodes that affected the region during the last 6 Ma. Eustatic changes (vicariant events) -not active range expansion of marine littoral ancestors colonizing desalinated habitats-explain the phylogeographic pattern observed in <it>M. longipes</it>.</p

Overcrowding in emergency department: an international issue

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Rituximab for the First-Line Maintenance Treatment of Follicular Non-Hodgkin’s Lymphoma

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin’s lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute’s Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG’s review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee’s (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44–0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG’s main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX

Quality improvement: theory and practice in healthcare

Ruth Boaden, Gill Harvey, Claire Moxham, Nathan Proudlov

Clinical scientist led transoesophageal echocardiography (TOE) - using extended roles to improve the service

At the North West Anglia NHS Foundation Trust we perform transoesophageal echocardiography (TOE), a semi-invasive diagnostic test using ultrasound for high-quality heart imaging. TOE allows accurate diagnosis of serious heart problems to support high-quality clinical decision-making about treatment pathways. The procedure can be lengthy and is traditionally performed by a consultant cardiologist, who typically has multiple commitments. This constrains patient access to TOE, leading to waits from referral to test, delaying treatment decisions. In this quality improvement project, we improved access by redesigning workforce roles. The clinical scientist, who had been supporting the consultant during TOE clinics, took on performing the procedure as the main operator. We used the Model for Improvement to develop this clinical-scientist-led service-delivery model, and then test and refine it. This increased capacity and frequency of TOE clinics, reducing waits and releasing around 2 days per month of consultant time. Over 5 plan-do-study-act cycles, we tested 6 changes/refinements. Our targets were to reduce the maximum waiting time for TOE to 3 working days for inpatients and to 14 working days for outpatients. We succeeded, achieving reductions in mean waiting times from 7.7 days to 3.0 days for inpatients and from 33.2 days to 8.3 days for outpatients. TOE requires intubation; when this fails, TOE is abandoned. We believe light (rather than heavy) sedation is helpful for this intubation. We reduced sedation levels (from a median of 3mg of Midazolam to 1.5mg) and, as a secondary outcome of this project, reduced the intubation failure rate from 13% to 0% (over 32 post-change patients). Following this project, our TOE service is usually performed by a clinical scientist in echocardiography who has British Society of Echocardiography TOE accreditation and advanced training. We have sustained the improved performance and demonstrated the value of enhanced roles for clinical scientists

Time to be more efficient: reducing wasted transthoracic echocardiography (TTE) diagnostic appointment slots at Guy’s and St Thomas’ NHS Trust

Transthoracic echocardiography (TTE) is one of the most requested non-invasive cardiac imaging diagnostic modalities available in the National Health Service (NHS). There is persistently high demand, but nationally, activity has lagged, producing increasing numbers of breaches of the 6-week waiting time target. This delays patients’ diagnosis and treatment.Patients attend hospital for TTE either as a clinic-linked or a standalone appointment. In this quality improvement project, we identified that the clinic-linked slots were a major source of wasted capacity due to both unbooked slots and a high rate of patients not attending their appointments (DNA).DNA is a complex issue, aggravated in our trust by many IT systems, complex clinic-booking pathways and restricted patient communication channels. We parked changing these processes, pending an imminent, unifying IT development programme. We focused instead on unused clinic-linked appointments, with the goal of reducing these from 18% (~31 of ~175 allocated each week) to 5% by the end of the 14 week project period.In close collaboration with service stakeholders, we identified that the primary root causes were related to the clinic-linked TTE booking pathway. The change idea was a 7-day rule: after reminders at 9 and 8 days prior to the clinic date, any appointment slots still unbooked by cardiology sub-specialities for patients attending clinic-linked appointments at 7 days, would be used for booking standalone TTE patients.We refined this process over two plan-do-study-act (PDSA) cycles, reducing unused (wasted) appointment slots, allocated initially to clinic-linked patients, to a sustained level of 5.1%, meaning we could now perform approximately 21 additional TTE tests weekly; we have materially increased activity without increasing capacity.This contributed to a significant reduction in 6-week TTE waiting-time breaches. Over the project, this went from 378 (30%, February 2022) to 71 (8%, September 2022) and latest data show 28 (4%, February 2023)