Lions, whales, and the web : transforming moment inertia into conservation action

When Farley Mowat wrote A Whale for the Killing in 1972, the titular fin whale, stranded and intentionally wounded in a Newfoundland pond, was long dead, yet the story of Moby Joe and the spectacle surrounding her death would become a cornerstone of the emerging anti-whaling movement (see below). The media frenzy that descended on the small town of Burgeo as the whale struggled to survive, and the subsequent publication of Mowat's book, are among the first examples of efforts to turn spontaneous outpourings of outrage, curiosity, or empathy into conservation action by actively focusing media attention, a phenomenon that we have dubbed moment inertia. We use “moment” because this phenomenon arises from focus of attention around a single, clarifying event, or moment, and “inertia” because that attention propagates, undirected, through media unless acted upon by outside forces, much like physical inertia. Almost half a century later, the events leading to the publication of A Whale for the Killing stand among the most effective uses of moment inertia in the conservation movement

The Coordination Chemistry of the N-Donor-Substituted Phosphazanes.

Phosph(III)azanes, featuring the heterocyclobutane P2 N2 ring, have now been established as building blocks in main-group coordination and supramolecular compounds. Previous studies have largely involved their use as neutral P-donor ligands or as anionic N-donor ligands, derived from deprotonation of amido-phosphazanes [RNHP(μ-NR)]2 . The use of neutral amido-phosphazanes themselves as chelating, H-bond donors in anion receptors has also been an area of recent interest because of the ease by which the proton acidity and anion binding constants can be modulated, by the incorporation of electron-withdrawing exo- and endo-cyclic groups (R) and by the coordination of transition metals to the ring P atoms. We observed recently that the effect of P,N-chelation of metal atoms to the P atoms of cis-[(2-py)NHP(μ-Nt Bu)]2 (2-py=2-pyridyl) not only pre-organises the N-H functionality for optimum H-bonding to anions but also results in a large increase in anion binding constants, well above those for traditional organic receptors like squaramides and ureas. Here, we report a broader investigation of ligand chemistry of [(2-py)NHP(μ-t NBu)]2 (and of the new quinolyl derivative [(8-Qu)NHP(μ-Nt Bu)]2 (8-Qu=8-quinolyl). The additional N-donor functionality of the heterocyclic substituents and its position has a marked effect on the anion and metal coordination chemistry of both species, leading to novel structural behaviour and reactivity compared to unfunctionalized counterparts.Cambridge Trus

Continuous cough monitoring using ambient sound recording during convalescence from a COPD exacerbation

Purpose Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent exacerbations and increased mortality. Cough increases during acute exacerbations (AE-COPD), representing a possible metric of clinical deterioration. Conventional cough monitors accurately report cough counts over short time periods. We describe a novel monitoring system which we used to record cough continuously for up to 45 days during AE-COPD convalescence. Methods This is a longitudinal, observational study of cough monitoring in AE-COPD patients discharged from a single teaching-hospital. Ambient sound was recorded from two sites in the domestic environment and analysed using novel cough classifier software. For comparison, the validated hybrid HACC/LCM cough monitoring system was used on days 1, 5, 20 and 45. Patients were asked to record symptoms daily using diaries. Results Cough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significantly from mean±SEM 272.7±54.5 on day 1 to 110.9±26.3 on day 9 (p<0.01) before plateauing. The absolute cough count detected by the continuous monitoring system was significantly lower than detected by the hybrid HACC/LCM system but normalised counts strongly correlated (r=0.88, p<0.01) demonstrating an ability to detect trends. Objective cough count and subjective cough scores modestly correlated (r=0.46). Conclusions Cough frequency declines significantly following AE-COPD and the reducing trend can be detected using continuous ambient sound recording and novel cough classifier software. Objective measurement of cough frequency has the potential to enhance our ability to monitor the clinical state in patients with COPD

A comparison of CFD and full-scale measurement for analysis of natural ventilation

CFD modelling techniques have been used to simulate the coupled external and internal flow in a cubic building with two dominant openings. CFD predictions of the time-averaged cross ventilation flow rates have been validated against full-scale experimental data under various weather conditions in England. RANS model predictions proved reliable when wind directions were near normal to the vent openings. However, when the fluctuating ventilation rate exceeded the mean flow, RANS models were incapable of predicting the total ventilation rate. Improved results are expected by applying more sophisticated turbulence models, such as LES or weighted quasi-steady approximations

Strategy for Mapping Quantitative Trait Loci (QTL) by Using Human Metapopulations

Aim: To present a novel strategy for mapping quantitative trait loci (QTL), using human metapopulations. The strategy is based on the expectation that in geographic clusters of small and distinct human isolates, a combination of founder effect and genetic drift can dramatically increase population frequency of rare QTL variants with large effect. In such cases, the distribution of QT measurements in an “affected” isolate is expected to deviate from that observed in neighboring isolates. Methods: We tested this hypothesis in 9 villages from a larger Croatian isolate resource, where 7 Mendelian disorders have been previously reported. The values of 10 physiological and biochemical QTs were measured in a random sample of 1001 individuals (100 inhabitants of each of 9 villages and 101 immigrant controls). Results: Significant over- or under- representation of individuals from specific villages in extreme ends of standardized QT measurement distribution was found 10 times more frequently than expected by chance. The large majority of such clusters of individuals with extreme QT values (34/36, 94.4%) originated from the 6 villages with the most pronounced geographic isolation and endogamy. Conclusion: Early epidemiological assessment supports the feasibility of the proposed strategy. Clusters of individuals with extreme QT values responsible for over-representation of single villages can usually be linked to a larger pedigree and may be useful for further QTL mapping, using linkage analysis

Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials?

Compared with smear microscopy, the Xpert MTB/RIF assay (Xpert), with superior accuracy and capacity to diagnose rifampicin resistance, has advanced TB diagnostic capability. However, recent trials of Xpert impact have not demonstrated reductions in patient morbidity and mortality. We conducted a narrative review of Xpert impact trials to summarize which patient-relevant outcomes Xpert has improved and explore reasons for no observed morbidity or mortality reductions. We searched PubMed, Google Scholar, Cochrane Library and Embase and identified eight trials meeting inclusion criteria: three individually randomized, three cluster-randomized, and two pre-post trials. In six trials Xpert increased diagnostic yield of bacteriologically-confirmed TB from sputa and in four trials Xpert shortened time to TB treatment. However, all-cause mortality was similar between arms in all six trials reporting this outcome, and the only trial to assess Xpert impact on morbidity reported no impact. Trial characteristics that might explain lack of observed impact on morbidity and mortality include: higher rates of empiric TB treatment in microscopy compared with Xpert arms, enrollment of study populations not comprised exclusively of populations most likely to benefit from Xpert, and health system weaknesses. So far as equipoise exists, future trials that address past limitations are needed to inform Xpert use in resource-limited settings

Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis

Mutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to synaptic alterations, we investigated synaptic ultrastructure and function in pre-symptomatic CTSD knock-out (Ctsd(−/−)) mice. Electron microscopy revealed that there were significantly greater numbers of readily releasable synaptic vesicles present in Ctsd(−/−) mice than in wild-type control mice as early as postnatal day 16. The size of this synaptic vesicle pool continued to increase with disease progression in the hippocampus and thalamus of the Ctsd(−/−) mice. Electrophysiology revealed a markedly decreased frequency of miniature excitatory postsynaptic currents (EPSCs) with no effect on pair-pulse modulation of the evoked EPSPs in the hippocampus of Ctsd(−/−) mice. The reduced miniature EPSC frequency was observed before the appearance of epilepsy or any morphological sign of synaptic degeneration. Taken together, the data indicate that CTSD is required for normal synaptic function, and that a failure in synaptic trafficking or recycling may be an early and important pathological mechanism in Ctsd(−/−) mice; these presynaptic abnormalities may initiate synaptic degeneration in advance of subsequent neuronal loss

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort

Abstract Background We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Methods Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Results Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75). Conclusions Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis