The Neogene rhinoceroses of Namibia

Since 1991 the Namibia Palaeontology Expedition has excavated four Miocene sites in the Sperrgebiet, three of which (Arrisdrift, Fiskus and Auchas Mine) are new. Only the material from Arrisdrift and a single bone from Langental are specifically determinable. All but one of the 81 rhinocerotid fossils from Arrisdrift constitute a homogeneous sample pertaining to a very large species of cursorial rhino. The exception is an isolated magnum which suggests a small to medium-sized short legged form, perhaps Chilotheridium pattersoni. A magnum from Langental probably represents Brachypotherium heinzelini. The large form from Arrisdrift seems to be the largest of the Miocene African Rhinos; the size and proportions of the metapodials and the other limb bones suggest an analogy with Diceros gr. pachygnathus-neumayri of the Upper Miocene of the Near East; the type of construction of the upper cheek teeth, namely die fourth premolar, is of Dicerotine type and presents, as do the dimensions, close resemblances with Diceros douariensis of the Upper Miocene of North Africa and Italy; the mandible shows analogies with the Dicerotines, especially the apparently short symphysis. This Rhino is Diceros australis nov. sp., so far the oldest known species of the subfamily.THE COUNCIL’S RESEARCH COMMITTEE, UNIVERSITY OF THE WITWATERSRAND. NATIONAL RESEARCH FOUNDATION (NRF

Reliability of the nitrogen washin-washout technique to assess end-expiratory lung volume at variable PEEP and tidal volumes

International audienceBackgroundEnd-expiratory lung volume measurement by the nitrogen washin-washout technique (EELVWI-WO) may help titrating positive end-expiratory pressure (PEEP) during acute respiratory distress syndrome (ARDS). Validation of this technique has been previously performed using computed tomography (EELVCT), but at mild PEEP levels, and relatively low fraction of inspired oxygen (FiO2), which may have insufficiently challenged the validity of this technique. The aims of this study were (1) to evaluate the reliability of EELVWI-WO measurements at different PEEP and V T during experimental ARDS and (2) to evaluate trending ability of EELVWI-WO to detect EELV changes over time.MethodsARDS was induced in 14 piglets by saline lavage. Optimal PEEP was selected during a decremental PEEP trial, based on best compliance, best EELVWI-WO, or a PEEP-FiO2 table. Eight V T (4 to 20 mL * kg-1) were finally applied at optimal PEEP. EELVWI-WO and EELVCT were determined after ARDS onset, at variable PEEP and V T.ResultsEELVWI-WO underestimated EELVCT with a non-constant linear bias, as it decreased with increasing EELV. Limits of agreement for bias were ±398 mL. Bias between methods was greater at high PEEP, and further increased when high PEEP was combined with low V T. Concordance rate of EELV changes between consecutive measurements was fair (79%). Diagnostic accuracy was good for detection of absolute EELV changes above 200 mL (AUC = 0.79).ConclusionsThe reliability of the WI-WO technique is critically dependent on ventilatory settings, but sufficient to accurately detect EELV change greater than 200 mL

Estimating Attributable Mortality Due to Nosocomial Infections Acquired in Intensive Care Units

Background. The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. Objective. TO assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. Setting. Eleven ICUs of a French university hospital. Design. We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was denned as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. Results. Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control Patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%—14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. Conclusions. ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assesse

Domestic Animals and Epidemiology of Visceral Leishmaniasis, Nepal

Proximity of Leishmania donovani–positive goats is a risk factor for human infection

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

BACKGROUND: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. METHODS: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. RESULTS: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems

Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk

Molecular and Evolutionary Bases of Within-Patient Genotypic and Phenotypic Diversity in Escherichia coli Extraintestinal Infections

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies