Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011

On 31 May 2011, after notification of Klebsiella pneumoniae(KP)(OXA-48);(CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), >= 1 Enterobacteriaceae(OXA-48) species (n=52)),of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KPOXA-48 and E. coli(OXA-48) for imipenem and meropenem ranged from = 16 mg/L, and 153/157 (97%) had MIC >0.25mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KPOXA-48;(CTX-M15); 107 KPCTX-M-15; 34 KPOXA-48). The 'oldest' KPCTX-M-15 and KPOXA-48 clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KPOXA-48 was detected in April 2012. Uncontrolled transmission of KP (CTX-M-15) evolved into a nosocomial outbreak of KPOXA-48; CTX-M15 with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify

Clinical, Genetic and Histopathological Characteristics of CRX-associated Retinal Dystrophies

PURPOSE: To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs). DESIGN: Retrospective multicenter cohort study including histopathology. SUBJECTS: Thirty-nine patients from 31 families with pathogenic variants in the CRX gene. METHODS: Clinical data of 152 visits were collected from medical records with a median follow-up time of 9.1 years (IQR, 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed. MAIN OUTCOME MEASURES: Visual acuity, retinal imaging, electroretinography (ERG), genotype-phenotype correlation, and histopathological examination were evaluated. RESULTS: The age at onset ranged from birth to the 8th decade of life. Median visual acuity was 1.00 logMAR (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Out of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis (LCA). In total, 21 different disease-associated heterozygous CRX variants were identified (10 missense, 8 frameshift, 2 deletion, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and two variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes. Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with extensive loss of photoreceptor nuclei and outer segments. CONCLUSION: This study illustrates the large clinical and genetic heterogenic spectrum of CRX-RDs, ranging from LCA to mild late-onset maculopathy resembling occult macular dystrophy. Haploinsufficiency and missense variants tended to be associated with milder phenotypes. Patients showed degeneration predominantly affecting the central retina on imaging. The histopathological findings also mirror these clinical findings and features similar to previously reported animal models of CRX-RDs

Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila

Protochlamydia amoebophila UWE25 is related to the Chlamydiaceae comprising major pathogens of humans, but thrives as obligate intracellular symbiont in the protozoan host Acanthamoeba sp. The genome of P. amoebophila encodes five paralogous carrier proteins belonging to the nucleotide transporter (NTT) family. Here we report on three P. amoebophila NTT isoforms, PamNTT2, PamNTT3 and PamNTT5, which possess several conserved amino acid residues known to be critical for nucleotide transport. We demonstrated that these carrier proteins are able to transport nucleotides, although substrate specificities and mode of transport differ in an unexpected manner and are unique among known NTTs. PamNTT2 is a counter exchange transporter exhibiting submillimolar apparent affinities for all four RNA nucleotides, PamNTT3 catalyses an unidirectional proton-coupled transport confined to UTP, whereas PamNTT5 mediates a proton-energized GTP and ATP import. All NTT genes of P. amoebophila are transcribed during intracellular multiplication in acanthamoebae. The biochemical characterization of all five NTT proteins from P. amoebophila in this and previous studies uncovered that these metabolically impaired bacteria are intimately connected with their host cell’s metabolism in a surprisingly complex manner

Review article: Towards a context-driven research: A state-of-the-art review of resilience research on climate change

The twofold aim of this paper is to provide an overview of the current state of resilience research with regard to climate change in the social sciences and propose a research agenda. Resilience research among social scientists is characterized by much more diversity today than a few decades ago. Different definitions and understandings of resilience appear in publications during the last 10 years. Resilience research increasingly bears the mark of social constructivism, a relative newcomer compared to the more long-standing tradition of naturalism. There are also approaches that are indebted to both "naturalism" and "constructivism", which, of course, come in many varieties. Based on our overview of recent scholarship, which is far from being exhaustive, we have identified six research avenues that arguably deserve continued attention. They combine naturalist and constructivist insights and approaches so that human agency, reflexivity, and considerations of justice and equity are incorporated into systems thinking research or supplement such research. Ultimately, we believe that the overarching challenge for future research is to ensure that resilience to climate change does not compromise sustainability and considerations of justice (including environmental, climate, and energy justice).

Retinal and choroidal thickness measurements using spectral domain optical coherence tomography in anterior and intermediate uveitis.

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Improved CARMA Locality Estimation Model for Peer List Reordering and Its Experimental Validation

The improvement of CARMA network model by addition of locality flavor as well as IPv6 support are concerned. The direct experimental evidence of the improvement of the efficiency of the peer-to-peer networks in terms of the network throughput using previously proposed CARMA locality awareness methods is established. The possible influences of the dynamics of the number of seeding and peering nodes in a swarm (including those directly connected to the test rig) are analyzed and taken into account. Main results indicate average 2,5 % improvement in transfer speed in comparison with clean unbiased transfer modes.Розглянуто вдосконалену реалізацію моделі CARMA, до якої додано новий клас локальності та обґрунтовано включення підтримки новітнього протоколу IPv6; також отримано пряме експериментальне підтвердження підвищення ефективності однорангових мереж із використанням попередньої версії оцінки локальності за моделлю CARMA. Проаналізовано та враховано вплив динаміки кількості завершених і незавершених вузлів у рої (включаючи ті, що прямо зв’язані з експериментальним стендом). Результати експериментів свідчать про підвищення середньої швидкості передачі на 2,5 % порівняно з немодифікованим режимом передачі.Рассмотрена усовершенствованная реализация модели CARMA, в которую добавлен новый класс локальности и обосновано включение поддержки новейшего протокола IPv6; также получено прямое экспериментальное подтверждение повышения эффективности одноранговых сетей с использованием предварительной версии оценки локальности по модели CARMA. Проанализировано и учтено влияние динамики количества завершенных и незавершенных узлов в рое (включая те, которые прямо связаны с экспериментальным стендом). Результаты экспериментов свидетельствуют о повышении средней скорости передачи на 2,5 % в сравнении с немодифицированным режимом передачи

Sociology Back to the Publics

This article is a reading of the `new sociology' that is mainly identified with the works of C. Wright Mills and Alvin Gouldner. Its main argument is that during the past 40 years the new sociology gave back a public face to sociology. This distinguishes it from the `old sociology' that had not been able to free itself from `private' social values. It is argued that Mills' power elite and Gouldner's coming crisis theses provided the foundation for a common enterprise among many `new sociologists' to develop a critical and public sociology that would seek to shape what Mills called the `democratic society of publics'.`New sociologists' share a critique of modern societies, namely, that though most modern societies have formal democracies, a substantial democratic social structure of publics is often lacking, due to the erosion of the public sphere by private values