Unlocking ground-based imagery for habitat mapping.

Fine-grained environmental data across large extents are needed to resolve the processes that impact species communities from local to global scales. Ground-based images (GBIs) have the potential to capture habitat complexity at biologically relevant spatial and temporal resolutions. Moving beyond existing applications of GBIs for species identification and monitoring ecological change from repeat photography, we describe promising approaches to habitat mapping, leveraging multimodal data and computer vision. We illustrate empirically how GBIs can be applied to predict distributions of species at fine scales along Street View routes, or to automatically classify and quantify habitat features. Further, we outline future research avenues using GBIs that can bring a leap forward in analyses for ecology and conservation with this underused resource.

Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1-3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5-7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11-13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14-16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18-20.

Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

How to: identify non-tuberculous Mycobacterium species using MALDI-TOF mass spectrometry.

BACKGROUND: The implementation of MALDI-TOF MS for microorganism identification has changed the routine of the microbiology laboratories as we knew it. Most microorganisms can now be reliably identified within minutes using this inexpensive, user-friendly methodology. However, its application in the identification of mycobacteria isolates has been hampered by the structure of their cell wall. Improvements in the sample processing method and in the available database have proved key factors for the rapid and reliable identification of non-tuberculous mycobacteria isolates using MALDI-TOF MS. AIMS: The main objective is to provide information about the proceedings for the identification of non-tuberculous isolates using MALDI-TOF MS and to review different sample processing methods, available databases, and the interpretation of the results. SOURCES: Results from relevant studies on the use of the available MALDI-TOF MS instruments, the implementation of innovative sample processing methods, or the implementation of improved databases are discussed. CONTENT: Insight about the methodology required for reliable identification of non-tuberculous mycobacteria and its implementation in the microbiology laboratory routine is provided. IMPLICATIONS: Microbiology laboratories where MALDI-TOF MS is available can benefit from its capacity to identify most clinically interesting non-tuberculous mycobacteria in a rapid, reliable, and inexpensive manner.

The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease.

BACKGROUND: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism. METHODS: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10-6, 10-5, 10-4mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235). RESULTS: 75 patients were enrolled. Following angiography, 60 patients (mean±SD age 57.5±8.5years; 80% male) were eligible and completed the protocol (n=30 RIPC, n=30 sham). The mean percentage change in coronary luminal diameter was -13.3±22.3% and -2.0±17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2- 21.4, p=0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01- 21.0, p=0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function. CONCLUSIONS: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC.

Development of nalidixic acid amphotericin B vancomycin (NAV) medium for the isolation of Campylobacter ureolyticus from the stools of patients presenting with acute gastroenteritis.

Recently, Campylobacter ureolyticus has been detected for the first time in the faeces of patients with acute gastroenteritis using polymerase chain reaction (PCR) techniques. Cultural isolation of C. ureolyticusis is not possible using the established selective methods for the isolation of thermophilic Campylobacter spp. from faeces. The aim of the current study is to develop a new selective medium capable of isolating C. ureolyticus from faecal samples. The newly-developed medium consists of Anaerobe Basal Agar with 10 g/L additional agar, 2 g/L sodium formate and 3 g/L sodium fumarate dibasic, to which 10 mg/L nalidixic acid, 10 mg/L amphotericin B and 20 mg/L vancomycin (NAV) are added as selective agents. Validation studies have shown that this experimental selective medium completely inhibits growth of Candida spp. and of Enterococcus spp. and permits reduced growth of selected coliforms and Proteus spp. Growth of Campylobacter ureolyticus on NAV medium is optimal in anaerobic and enriched hydrogen atmospheres. Additionally, an overnight enrichment step using Bolton broth to which 2 g/L sodium formate, 3 g/L sodium fumarate dibasic and the NAV supplement are added, in place of the commercial Bolton broth supplement, allows improved recovery of C. ureolyticus from patients' faeces.

Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns.

BACKGROUND: Extremely preterm babies (delivered at <28 completed weeks of gestation) are frequently diagnosed with hypotension and treated with inotropic and pressor drugs in the immediate postnatal period. Dopamine is the most commonly used first-line drug. Babies who are treated for hypotension more frequently sustain brain injury, have long-term disability or die compared to those who are not. Despite the widespread use of drugs to treat hypotension in such infants, evidence for efficacy is lacking, and the effect of these agents on long-term outcomes is unknown. HYPOTHESIS: In extremely preterm babies, restricting the use of dopamine when mean blood pressure (BP) values fall below a nominal threshold and using clinical criteria to determine escalation of support ('restricted' approach) will result in improved neonatal and longer-term developmental outcomes. RESEARCH PLAN: In an international multi-centre randomised trial, 830 infants born at <28 weeks of gestation, and within 72 h of birth, will be allocated to 1 of 2 alternative treatment options (dopamine vs. restricted approach) to determine the better strategy for the management of BP, using a conventional threshold to commence treatment. The first co-primary outcome of survival without brain injury will be determined at 36 weeks' postmenstrual age and the second co-primary outcome (survival without neurodevelopmental disability) will be assessed at 2 years of age, corrected for prematurity. DISCUSSION: It is essential that appropriately designed trials be performed to define the most appropriate management strategies for managing low BP in extremely preterm babies.

[Precancerous tumors and carcinomas in situ of the skin]. / Präkanzerosen und Carcinomata in situ der Haut.

Precancerous skin lesions and carcinomas in situ of the skin represent the early stages of epithelial skin tumors. There is no invasive tumor growth, so the basement membrane is completely intact. These lesions show a wide variation of clinical and histological appearances on the skin or mucosa. The precancerous and carcinoma in situ lesions that are described in this text are actinic keratosis, actinic cheilitis, cutaneous horns, arsenical keratosis, tar-induced dermatosis, X-ray irradiation-related keratosis, Bowen's disease, erythroplasia of Queyrat, bowenoid papulosis, intraepithelial neoplasia (vulvar, penile and anal). Because they all can progress into invasive carcinoma, therapy is mandatory. Many noninvasive therapeutic approaches exist nowadays in the form of gels, creams, photodynamic therapy and invasive techniques such as laser therapy and cryotherapy, curettage and excision of lesional skin. Depending on the treatment process, different rates of general clearance and recurrence of the lesions are discussed in this article.

Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum ß-lactamase-producing coliforms and meticillin-resistant Staphylococcus aureus.

A restrictive antibiotic policy banning routine use of ceftriaxone and ciprofloxacin was implemented in a 450-bed district general hospital following an educational campaign. Monthly consumption of nine antibiotics was monitored in defined daily doses (DDDs) per 1000 patient-occupied bed-days (1000 pt-bds) 9 months before until 16 months after policy introduction. Hospital-acquired Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase (ESBL)-producing coliform cases per month/1000 pt-bds were identified and reviewed throughout the hospital. Between the first and final 6 months of the study, average monthly consumption of ceftriaxone reduced by 95% (from 46.213 to 2.129 DDDs/1000 pt-bds) and that for ciprofloxacin by 72.5% (109.804 to 30.205 DDDs/1000 pt-bds). Over the same periods, hospital-acquisition rates for C. difficile reduced by 77% (2.398 to 0.549 cases/1000 pt-bds), for MRSA by 25% (1.187 to 0.894 cases/1000 pt-bds) and for ESBL-producing coliforms by 17% (1.480 to 1.224 cases/1000 pt-bds). Time-lag modelling confirmed significant associations between ceftriaxone and C. difficile cases at 1 month (correlation 0.83; P<0.005), and between ciprofloxacin and ESBL-producing coliform cases at 2 months (correlation 0.649; P=0.002). An audit performed 3 years after the policy showed sustained reduction in C. difficile rates (0.259 cases/1000 pt-bds), with additional decreases for MRSA (0.409 cases/1000 pt-bds) and ESBL-producing coliforms (0.809 cases/1000 pt-bds). In conclusion, banning two antibiotics resulted in an immediate and profound reduction in hospital-acquired C. difficile, with possible longer-term effects on MRSA and ESBL-producing coliform rates. Antibiotic stewardship is fundamental in the control of major hospital pathogens.

Molecular-based mycobacterial identification in a clinical laboratory setting: a comparison of two methods.

Many mycobacterial species are pathogenic to humans, with infection occurring worldwide. Infection with Mycobacterium tuberculosis is a well-described global phenomenon, but other mycobacterial species are increasingly shown to be the cause of both pulmonary and extrapulmonary infection and are managed differently from M. tuberculosis infection. Rapid and accurate differentiation of mycobacterial species is, therefore, critical to guide timely and appropriate therapeutic and public health management. This study evaluates two commercially available DNA strip assays, the Genotype Common Mycobacteria (CM) assay (Hain Lifescience, Nehren, Germany) and the Speed-oligo Mycobacteria assay (Vircell, Spain) for their usefulness in a clinical laboratory setting. Both assays were evaluated on 71 clinical mycobacterial isolates, previously identified using Gen-Probe AccuProbe and through a UK mycobacteriology reference laboratory, as well as 29 non-mycobacterial isolates. Concordant results were obtained for 98% of isolates using both assays. The sensitivity was 97% (95% confidence interval [CI]: 93.3-100%) for the CM assay and 98.6% (95% CI: 95.9-100%) for the Speed-oligo assay. Overall, both assays proved to be useful tools for rapid and sensitive mycobacterial species identification, although interpretation of results was easier with the CM assay. Finally, results were available within one day, compared to current identification times which range between seven days and four weeks.

Molecular-based detection of non-culturable and emerging campylobacteria in patients presenting with gastroenteritis.

From January 2009 to May 2010, 436 faecal samples from patients with diarrhoeal illness in Southern Ireland were identified as Campylobacter genus-positive by an automated multiplex PCR; however, 204 (46·8%) of these samples were culture-negative for campylobacters. A combination of Campylobacter-specific uniplex PCR and 16S rRNA sequencing confirmed the presence of Campylobacter DNA in 191 (93·6%) of the culture-negative samples. Species-specific PCR identified C. jejuni (50·7%) C. ureolyticus (41%) and C. coli (5·7%) as the most prevalent species while C. fetus, C. upsaliensis, C. hyointestinalis and C. lari accounted for 10% of culture-negative samples; mixed Campylobacter spp. were detected in 11% of samples. We conclude that non-culturable Campylobacter spp. are responsible for a considerable proportion of human enteritis and the true incidence of infection is likely to be significantly underestimated where conventional Campylobacter culture methods are used in isolation.

Validation of a norovirus multiplex real-time RT-PCR assay for the detection of norovirus GI and GII from faeces samples.

Norovirus is a leading cause of infectious non-bacterial gastroenteritis. The virus is highly contagious and has multiple modes of transmission, presenting a growing challenge to hospital-based healthcare. In this study, a total of 120 stool samples are tested for the presence of norovirus GI and GII by the Roche two-step Lightcycler 2.0 assay incorporating primers and probes produced by TIB Molbiol, and the results are compared with results from the National Virus Reference Laboratory. The Roche/TIB Molbiol assay produced 51 positive results and 69 negative results. Discrepancy analysis was performed for six conflicting results using a second real-time polymerase chain reaction (PCR) assay (Roche/TIB Molbiol) and this confirmed that four of the five discrepant positive results were true positives. A single discrepant negative result generated by the Roche assay remained negative using the second assay. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to be 98%, 98.6%, 98.0% and 98.6%, respectively. Melting curve analysis was used to differentiate genogroups I and II and this showed that 92% of strains belonged to genogroup II.

An unusual case of Legionellosis.

Legionella species is a common cause of community-acquired pneumonia. However disease due to L. pneumophila serogroup 13 is rare and has not previously been reported in Ireland. It may not be detected by routine Legionella antigen and antibody kits. Due to these limitations, early culture should be considered when legionellosis is suspected. The potential therapeutic benefit of quinolones in the management of this disease is also illustrated.

The role of biopsy in the diagnosis of infections of the central nervous system.

CNS infections require prompt appropriate therapy, but do not usually require tissue biopsy for diagnosis. We performed a 5 year audit of CNS infections which required brain or spinal biopsy to determine or confirm a diagnosis of CNS infection. Sixteen cases were identified in which clinical, radiological or additional investigations including culture, serology or PCR for the suspected specific infective agents were not diagnostic. 6 (37.5%) were bacterial abscesses presenting as space-occupying intracerebral lesions with a differential diagnosis of neoplasm. There were 3 (18.7%) cases of toxoplasmosis and 2 (12.5%) cases of aspergillosis. There was one case (6.2%) of herpes simplex encephalitis, one cysticercosis and one progressive multifocal leucoencephalopathy, all biopsied as possible neoplasms. There were 2 (12.5%) cases of spinal tuberculosis, one multifocal, mimicking neurofibromatosis. This review highlights the usefulness of targeted biopsy in the rapid diagnosis of CNS infections. It also emphasizes the lack of specificity of 'negative' culture and serology in certain cases, especially in the setting of immune-compromise.

[Human papillomavirus-associated warts in organ transplant recipients. Incidence, risk factors, management]. / Humane Papillomvirus-assoziierte Warzen bei organtransplantierten Patienten. Inzidenz, Risikofaktoren, Management.

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially identifying patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.

Reflectance confocal microscopy for noninvasive monitoring of therapy and detection of subclinical actinic keratoses.

BACKGROUND: Actinic keratoses (AK) represent cutaneous carcinoma in situ and have previously been evaluated by reflectance confocal microscopy (RCM). Treatment of AK with imiquimod (IMIQ) 5% cream has been shown to 'highlight' subclinical lesions. OBJECTIVE: The aim of this study was to test the applicability of RCM for noninvasive monitoring of actinic field cancerization and detection of subclinical AK. SUBJECTS AND METHODS: AK and surrounding skin sites with no apparent AK of 11 volunteers were selected for imaging and subsequently classified as 'clinical' and 'subclinical' AK. IMIQ was used 3 times weekly for 4 weeks. RESULTS: RCM was able to detect morphologic features of AK in both clinical and subclinical AK; features were more pronounced in clinical lesions. The immunomodulatory response induced by IMIQ was visualized by RCM. CONCLUSION: Our findings indicate that RCM allows noninvasive monitoring of treatment response in vivo and permits early detection of subclinical AK, thus substantiating the incentive for therapy.