The tooth, the whole tooth and nothing but the tooth: tooth shape and ontogenetic shift dynamics in the white shark Carcharodon carcharias.

Results from this study of the white shark Carcharodon carcharias include measurements obtained using a novel photographic method that reveal significant differences between the sexes in the relationship between tooth cuspidity and shark total length, and a novel ontogenetic change in male tooth shape. Males exhibit broader upper first teeth and increased distal inclination of upper third teeth with increasing length, while females do not present a consistent morphological change. Substantial individual variation, with implications for pace of life syndrome, was present in males and tooth polymorphism was suggested in females. Sexual differences and individual variation may play major roles in ontogenetic changes in tooth morphology in C. carcharias, with potential implications for their foraging biology. Such individual and sexual differences should be included in studies of ontogenetic shift dynamics in other species and systems.

Making a difference in the real world. User-centred impact evaluation of an eight-country, community-based early childhood programme.

This paper presents a unique approach to the Impact Evaluation of a project that focused on low-threshold intergenerational play-based interactions in order to support young children from marginalised communities in eight European countries. The approach builds upon the work of Fetterman's Empowerment Evaluation and Patton's Utilization Focused Evaluation and brings them together to form an adapted model of evaluation. We outline in this paper how these two well developed methods of evaluation have been applied to a real world context, that is, the impact evaluation of a complex international project. Our approach highlights the complexities of differing contexts and allows for surprising and unintended consequences to emerge. It results, through double loop learning, a type of feedback loop with the internal stakeholders and implementers that is useful to the project coordination team, with a view to further upscaling of the initiative. Recommendations for policy at local, national and European Union levels were provided to the project and potential external users. However, the predominant feedback was provided at two crucial points along the way; during a stakeholder mapping exercise and during the further development of monitoring data tools.

Prevalence and role of efflux pump activity in ciprofloxacin resistance in clinical isolates of Klebsiella pneumoniae.

We investigated the prevalence and role of efflux pump activity and possible drug influx resistance in ciprofloxacin susceptibility amongst 26 distinct clinical isolates of Klebsiella pneumoniae of varying ciprofloxacin susceptibilities and known quinolone resistance-determining region (QRDR) genotypes. Cellular [(14)C]ciprofloxacin accumulation patterns and the amount of cell-associated [(14)C]ciprofloxacin of mid-logarithmic phase cells were determined before and after challenging with the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Most isolates (24/26), and all with ciprofloxacin minimum inhibitory concentrations (MICs) >1 µg/ml, had efflux activity that could extrude up to 90% of cell-associated [(14)C]ciprofloxacin; none had significant influx resistance. In isolates with no QRDR mutations, efflux alone reduced ciprofloxacin susceptibility. In isolates with QRDR mutations, the efflux activity varied: in one isolate with no efflux activity, the most common fluoroquinolone resistance-causing QRDR mutation did not bring about clinically significant ciprofloxacin resistance; isolates with multiple mutations had high MICs and, usually, high levels of efflux activity. Fluoroquinolone efflux activity is much more common in clinical isolates of K. pneumoniae than previously reported and it can contribute to decreased ciprofloxacin susceptibility.

Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.

PURPOSE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are classically characterised by susceptibility to most non-ß-lactam antimicrobial agents. We sought to determine whether antimicrobial susceptibility (AMS)-based algorithms could be used to presumptively identify CA-MRSA in a hospital MRSA collection. METHODS: Over a three-month period, all MRSA were tested for AMS, staphylococcal cassette chromosome mec (SCCmec) type, presence of the Panton-Valentine leukocidin (PVL) genes and spa type. CA-MRSA isolates were defined genotypically using a combination of spa and SCCmec type. AMS based algorithms were developed and tested for their sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Ciprofloxacin susceptibility (p < 0.001) and fusidic acid resistance (p = 0.044) were independent predictors of CA-MRSA in a multivariate model. Although 98.5% of HA-MRSA were ciprofloxacin resistant, so too were 36.6% of CA-MRSA. Algorithms based on ciprofloxacin-susceptibility and fusidic acid resistance performed best, with specificity and NPV >90% and sensitivity and PPV >70%. CONCLUSIONS: Our data indicate that while ciprofloxacin-susceptible isolates are likely to be CA-MRSA, the use of ciprofloxacin-susceptibility as a marker of CA-MRSA would miss approximately one third of CA-MRSA isolates. Therefore, AMS patterns have limited utility for the identification of genetically-defined CA-MRSA in our setting.

Korean hemorrhagic fever: propagation of the etiologic agent in a cell line of human origin.

The etiologic agent of Korean hemorrhagic fever has been propagated in a human cultured cell line derived from a carcinoma of the lung. The cells, described as type II, alveolar epithelial, support replication of the agent and successive passages. Antigen of the Korean hemorrhagic fever agent is readily detected in infected cells by means of direct or indirect fluorescent antibody techniques. Previous attempts to propagate this agent in vitro had been unsuccessful.

Comparison of community-associated methicillin-resistant Staphylococcus aureus from teaching hospitals in London and the USA, 2004-2006: where is USA300 in the UK?

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasingly common in the USA, but rare in the UK. We compared CA-MRSA from the UK and USA to examine differences in the molecular epidemiology. We investigated patients presenting with MRSA in the first 72 h of hospital admission or in out-patient settings in a UK and a US hospital from January 2004 to March 2006. Fluoroquinolone susceptibility was used as a screening marker to select presumptive CA-MRSA. One hundred and eighteen and 49 such strains were identified, representing a prevalence of 0.1 and 0.2 isolates per 1,000 patient days in the UK and US respectively. Panton-Valentine leukocidin (PVL)-positive ST8-IVa (USA300)-type strains predominated among 43 surviving US isolates, whereas PVL-negative ST1-IVa predominated among 71 surviving UK isolates. There are striking differences between the molecular epidemiology of CA-MRSA in UK and US hospitals, which may have implications for control.

Bacterial contamination on touch surfaces in the public transport system and in public areas of a hospital in London.

AIMS: To investigate bacterial contamination on hand-touch surfaces in the public transport system and in public areas of a hospital in central London. METHODS AND RESULTS: Dipslides were used to sample 118 hand-touch surfaces in buses, trains, stations, hotels and public areas of a hospital in central London. Total aerobic counts were determined, and Staphylococcus aureus isolates were identified and characterized. Bacteria were cultured from 112 (95%) of sites at a median concentration of 12 CFU cm(-2). Methicillin-susceptible Staph. aureus (MSSA) was cultured from nine (8%) of sites; no sites grew methicillin-resistant Staph. aureus (MRSA). CONCLUSIONS: Hand-touch sites in London are frequently contaminated with bacteria and can harbour MSSA, but none of the sites tested were contaminated with MRSA. SIGNIFICANCE AND IMPACT OF THE STUDY: Hand-touch sites can become contaminated with staphylococci and may be fomites for the transmission of bacteria between humans. Such sites could provide a reservoir for community-associated MRSA (CA-MRSA) in high prevalence areas but were not present in London, a geographical area with a low incidence of CA-MRSA.

Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.

These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Sex, size and isotopes: cryptic trophic ecology of an apex predator, the white shark Carcharodon carcharias.

Demographic differences in resource use are key components of population and species ecology across the animal kingdom. White sharks (Carcharodon carcharias) are migratory, apex predators, which have undergone significant population declines across their range. Understanding their ecology is key to ensuring that management strategies are effective. Here, we carry out the first stable isotope analyses of free-swimming white sharks in South Africa. Biopsies were collected in Gansbaai (34.5805°S, 19.3518°E) between February and July 2015. We used Stable Isotope Bayesian Ellipsis in R and traditional statistical analyses to quantify and compare isotopic niches of male and female sharks of two size classes, and analyse relationships between isotopic values and shark length. Our results reveal cryptic trophic differences between the sexes and life stages. Males, but not females, were inferred to feed in more offshore or westerly habitats as they grow larger, and only males exhibited evidence of an ontogenetic niche shift. Lack of relationship between δ13C, δ15N and female shark length may be caused by females exhibiting multiple migration and foraging strategies, and a greater propensity to travel further north. Sharks < 3 m had much wider, and more diverse niches than sharks > 3 m, drivers of which may include individual dietary specialisation and temporal factors. The differences in migratory and foraging behaviour between sexes, life stages, and individuals will affect their exposure to anthropogenic threats, and should be considered in management strategies.

Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.

We report the identification and control of an outbreak of a ciprofloxacin-susceptible strain of UK epidemic meticillin-resistant Staphylococcus aureus (EMRSA)-15 on a neonatal unit (NNU). All babies were screened for MRSA on admission using ciprofloxacin-containing media which did not detect the outbreak strain. The first identified case was a premature baby who developed MRSA bacteraemia with associated tibial osteomyelitis and multiple subcutaneous abscesses. The outbreak strain was subsequently identified in the nasopharyngeal secretions of a second child who was not clinically infected. Screening of all patients on the NNU using non-ciprofloxacin-media identified two other colonised babies. All four patient isolates were EMRSA-15, spa type t022, SCCmec IV, Panton-Valentine leucocidin (PVL) negative, indistinguishable by pulsed-field gel electrophoresis and susceptible to all non-beta-lactam antimicrobials tested. The outbreak strain was cultured from four of 48 environmental sites in a communal milk-expressing room. Unsupervised movement of mothers to and from the milk-expressing room may have contributed to the outbreak. Control measures included cohort isolation of affected babies, improved environmental cleaning, increased emphasis on hand hygiene and education of mothers. Ciprofloxacin-containing media should be used with caution for MRSA screening in settings where ciprofloxacin-susceptible strains (including community-associated MRSA) are increasing in prevalence.

Point-of-care universal screening for meticillin-resistant Staphylococcus aureus: a cluster-randomized cross-over trial.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is frequently endemic in healthcare settings and may be transmitted by person-to-person spread. Asymptomatic MRSA carriers are potential, unsuspected sources for transmission and some of them may be identified by admission screening. AIM: To assess whether rapid point-of-care screening (POCS) for MRSA at hospital admission may be associated with a reduction in MRSA acquisition rates when compared with slower laboratory-based methods. METHODS: A cluster-randomized cross-over trial was conducted in four admission wards of an acute London tertiary care hospital. Polymerase chain reaction-based POCS screening was compared with conventional culture screening. Patients were screened on ward admission and discharge, and the MRSA acquisition rate on the admission wards was calculated as the primary outcome measure. RESULTS: In all, 10,017 patients were included; 4978 in the control arm, 5039 in the POCS arm. The MRSA carriage rate on admission was 1.7%. POCS reduced the median reporting time from 40.4 to 3.7 h (P < 0.001). MRSA was acquired on the admission wards by 23 (0.46%) patients in the control arm and by 24 (0.48%) in the intervention arm, acquisition rates of 5.39 and 4.60 per 1000 days respectively. After taking account of predefined confounding factors, the adjusted incidence rate ratio (IRR) for change in trend for MRSA acquisition was 0.961 (95% confidence interval: 0.766-1.206). The adjusted IRR for step change for MRSA acquisition was 0.98 (0.304-3.162). CONCLUSION: POCS produces a significantly faster result but has no effect on MRSA acquisition on admission wards compared with culture screening. Where compliance with infection prevention and control is high and MRSA carriage is low, POCS has no additional impact on MRSA acquisition rates over the first one to four days of admission compared with conventional culture screening.

Enhanced surveillance of meticillin-resistant Staphylococcus aureus bacteraemia in a London teaching hospital.

In 2001, the UK Department of Health introduced mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias (blood-culture-positive episodes) in English hospitals. We performed enhanced surveillance in their hospital between April 2001 and March 2003 to determine the epidemiology of MRSA bacteraemia across different specialities. There were 267 MRSA-blood-culture-positive episodes, giving a rate of 0.37 per 1000 occupied bed-days (OBD). Thirty-three (12.4%) episodes were false positives due to contaminants and 15 (5.6%) originated in the community or at another institution. Thirty-one (11.6%) episodes were in outpatients or occurred after recent discharge and were designated 'hospital associated'. The remaining 188 cases were clinically significant hospital-acquired episodes in inpatients, with a rate of 0.26 per 1000 OBDs. The highest rates were in the intensive therapy unit (ITU; 2.74 per 1000 OBDs) and the high-dependency unit (HDU; 1.68 per 1000 OBDs). Fifty-five non-ITU, non-HDU episodes occurred in patients who had been discharged from ITU or HDU prior to the development of bacteraemia but during the same admission. The number of MRSA bacteraemias related to ITU/HDU suggests that these wards may be hubs of MRSA infection. Haematology, oncology and renal (HOR) patients had the greatest number of hospital-associated episodes. The most common source of MRSA bacteraemia was a vascular access device (VAD) (108 episodes, 57%, 64% of which were central lines). The high bacteraemia rates in ITU, HDU and HOR patients were associated with high usage of VADs. The majority of episodes occurred in patients who were newly colonized with MRSA after admission. Thus, in this hospital, VADs and stays in ITU or HDU are important risk factors for bacteraemia, and VAD care and prevention of cross-infection are priorities for intervention. We recommend that the mandatory national surveillance scheme should collect additional data on MRSA bacteraemia to provide information for a national strategy for MRSA control and to allow appropriate comparison between institutions.

Guidelines for the control of glycopeptide-resistant enterococci in hospitals.

The increase since the mid 1980s in glycopeptide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

A randomised trial comparing 5 mL/kg and 10 mL/kg of pentastarch as a volume preload before spinal anaesthesia for elective caesarean section.

BACKGROUND: Colloid solutions are more effective at preventing hypotension than crystalloids when used as a volume preload before caesarean delivery under spinal anaesthesia. The ideal volume to infuse has not been established. METHOD: In a randomised double-blind trial 70 women presenting for elective caesarean section received either 5 mL/kg of pentastarch (group A) or 10 mL/kg of pentastarch (group B) as a volume preload before spinal anaesthesia. Hypotension was defined as a systolic pressure below 90 mmHg or a decrease of 30% from a baseline value. Treatment was with 6-mg increments of ephedrine until resolution. RESULTS: In group B, 7/35 patients (20%) developed hypotension, significantly fewer than the 15/35 (42.8%) in group A (P<0.05). The patients in group B also required less ephedrine (total in group, 114 mg) than those in group A (total in group, 198 mg) CONCLUSIONS: Pentastarch, 10 mL/kg is more effective than 5 mL/kg at preventing hypotension following spinal anaesthesia for caesarean delivery.

Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors.

Kirsten-ras-revertant-1 (Krev-1/Rap1A) is a recently identified tumor suppressor gene which induces flat revertants when introduced into a variety of ras-transformed cell lines in vitro. Since 47% of colorectal carcinomas have transforming mutations in ras protooncogenes, and since Krev-1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the Krev-1 locus may be necessary for transformation of colonic cells. Loss of heterozygosity is a common method of inactivation of tumor suppressor genes in colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients with sporadic colorectal cancer. Because Krev-1 had no previously described polymorphisms, we first identified a BclI restriction fragment length polymorphism which showed 40% heterozygosity in 50 unrelated individuals. However, only one tumor from 18 informative patients showed allelic loss at the Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the Krev-1 locus in colorectal cancer. However, the results do not exclude a role for Krev-1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.

Clinical impact and relevance of antibiotic resistance.

Increasing antimicrobial resistance and multiple resistance have resulted in increasing difficulties in the treatment of bacterial infections. Resistance leads to inappropriate empirical therapy, delay in starting effective treatment, and the use of less effective, more toxic, and more expensive drugs. Although studies are not always consistent, antimicrobial resistance in the infecting organisms is associated with treatment failure, prolonged or additional hospitalization, increased costs of care, and increased mortality. Additional costs and lost bed days are incurred by the need to control the spread of antimicrobial-resistant organisms within hospitals. All this has significant direct impact on patients and their families and also secondary effects on the cost effectiveness of healthcare delivery. There is an urgent need to control antimicrobial resistance by improved antibiotic usage and reduction of hospital cross-infection.

Significant reduction of endemic MRSA acquisition and infection in cardiothoracic patients by means of an enhanced targeted infection control programme.

Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in cardiothoracic patients at St Thomas' Hospital, an enhanced infection control programme was introduced in September 2000. It was based on UK national guidelines on the control of MRSA and targeted additional identified risk factors for surgical site infection (SSI). It included recognition of the problem by senior staff and their taking responsibility for it; intensive support, education and advice from the infection control team; improved ward and theatre hygiene; pre-admission, admission and weekly MRSA screening; isolation and clearance treatment; nursing care pathways for MRSA colonized patients; and teicoplanin plus gentamicin surgical prophylaxis. The effectiveness of the programme was assessed by retrospective analysis of computerized patient data for the 16 months before and after the introduction of the programme. There was no significant change in the number of operations or the proportion of patients admitted with MRSA, although nine patients were cleared of carriage before admission. However, there were significant falls in the proportion of patients acquiring MRSA on the ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20-23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and 16/1075 to 7/956, respectively) but this did not reach statistical significance. These results demonstrate that an enhanced, targeted infection control programme based on the UK national guidelines, SSI prevention guidelines and local risk assessment can reduce the incidence of nosocomial MRSA acquisition and invasive infection in cardiothoracic patients in the face of continuing endemic risk.

Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG.

Chronic loose constriction of the sciatic nerve produces mechanoallodynia and thermal hyperalgesia in rats and mice, and the behaviour develops during the time in which the nerve distal to the ligature site is undergoing Wallerian degeneration. There is a sympathetic component to the pain generated by this and other rodent models of neuropathic pain, yet the site at which this sympathetic-sensory coupling remains unknown. It has been shown that following sciatic nerve transection or spinal nerve lesion, sympathetic axons invade the dorsal root ganglion (DRG) where they sometimes form pericellular baskets around mostly large diameter DRG neurons--a possible anatomical substrate for sympathetically maintained pain (SMP). The signal for the sympathetic invasion of the DRG has not yet been shown, but associated with Wallerian degeneration is the upregulation of nerve growth factor (NGF) in the distal stump of the partially injured nerve, which may be retrograde-transported to the DRG in uninjured sensory axons to induce sprouting of sympathetic axons. To investigate the role of Wallerian degeneration in the development of neuropathic pain and sympathetic sprouting in the DRG, we have made use of a strain of mouse (C57B1/Wld) in which Wallerian degeneration following nerve injury is delayed. We gave wild-type or Wld mice chronic constriction injuries (CCI) by loosely ligating the sciatic nerve with 3 ligatures, and allowed these mice to survive for a further 1, 2 or 3 weeks, during which time we assessed mechanoallodynia and thermal hyperalgesia. At the end of the testing period, the lumbar DRGs were removed for glyoxylic acid-induced fluorescence of catecholamines to determine the extent to which sympathetic axons had invaded the DRG. We found that both indices of neuropathic pain were significantly attenuated in Wld mice compared to wild-type mice, with the wild-type mice increasing in sensitivity to both thermal and mechanical stimulation in the first week post-operative (PO), while Wld mice showed marked hypoalgesia following CCI. Histological examination of the DRG showed that sympathetic sprouting into the DRG was also markedly delayed in Wld mice compared to wild-type mice: 1 week following injury, sympathetic fibres had invaded the ipsilateral DRG of wild-type mice, while sprouting in ipsilateral DRG of Wld mice was only slightly increased at 3 weeks PO. These results show that Wallerian degeneration is tightly linked to the development of both pain and sympathetic sprouting following CCI, and we speculate on the possible role of NGF as a mediator of both phenomena.