A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae.

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings

A study of indium nitride films grown under conditions resulting in apparent band-gaps from 0.7 eV to 2.3 eV

The band-gap of indium nitride has long been believed to be about 1.9eV with slight variations due to band-tailing in polycrystalline samples and degenerate doping. Recently, other values as low as 0.7 eV have apparently been observed. We have compared samples spanning this apparent range of band-gap using secondary ion mass spectroscopy (SIMS), X-ray Photoelectron Spectroscopy (XPS) and heavy ion elastic recoil detection analysis (ERDA), in conjunction with spectral optical density measurements. Once structural inhomogeneiteies are taken into account, we show that much of the conflicting data are compatible with direct photoionisation with a threshold energy of about 1.0eV. This feature was first reported in polycrystalline indium nitride over 15 years ago and attributed to a |p> like defect state. We ask whether the feature may instead be a direct band-gap.6 page(s

Not Every Snoring Is Obstructive Sleep Apnea (OSA): Plasma Cell Neoplasm Masquerading as OSA

Introduction: Obstructive sleep apnea is a common condition characterized by recurrent upper airway obstruction during sleep, inducing hypoxia and sleep fragmentation. Plasma cell neoplasms are a group of commodities characterized by the neoplastic expansion of clonal plasma cells, which can be present as a single lesion (solitary plasmacytoma) or numerous lesions (multiple myeloma). We present an intriguing case of plasma cell neoplasm causing tracheal compression simulating OSA. Case Description: A 39-year-old morbidly obese male with no past medical history presented with excessive fatigue, heavy snoring, and pauses in breathing during sleep. He denied shortness of breath, wheezing, and orthopnea. On physical exam, his neck circumference was 45 cm. On screening with the STOP-BANG questionnaire, he had a high risk of OSA with a score of 6 points. The patient underwent a home sleep study showing moderate sleep apnea with an Apnea Hypopnea Index (AHI) of 23.2, followed by a CPAP titration study with a recommended pressure of 13 cm H2O. However, even after three months, the patient\u27s symptoms did not improve. Moreover, he started complaining of worsening shortness of breath and exercise intolerance. A pulmonary function test (PFT) demonstrated a combined moderately severe obstructive and restrictive defect with no significant bronchodilator response and normal DLCO. Echocardiogram was normal with EF of 65%. A chest CT scan showed multiple polypoid lesions in the upper trachea, left lower lobe bronchus, and right bronchus intermedius. The patient underwent diagnostic bronchoscopy with endobronchial biopsies with tumor debulking. The biopsy showed diffuse plasma cell infiltrate with mature features with immunohistochemistry positive for CD138+ plasma cells with kappa light chain restriction, features suggestive of plasma cell neoplasm. Discussion: OSA is a common sleep-related disorder with a prevalence of up to 15 to 30% in the United States. Common risk factors include age, male sex, obesity, upper airway, and craniofacial abnormalities. The patient usually presents with daytime somnolence, loud snoring, gasping, choking, or pauses in breathing while sleeping. The diagnosis is confirmed with polysomnography, and treatment includes positive airway pressure therapy. However, numerous organic causes that can compress mimic OSA secondary to compression of the airways, like the plasma cell neoplasm compressing the trachea in our case. Therefore, other differentials should also be considered in some instances, especially if the symptoms are not improved or worsened despite the treatment of OSA

Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal

BACKGROUND Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking. METHODS In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing. RESULTS A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P CONCLUSIONS A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161. opens in new tab.)</p