Missed opportunities for tuberculosis prevention among patients accessing a UK HIV service.

United Kingdom guidelines recommend screening for and treatment of latent tuberculosis infection (LTBI) in HIV-positive patients at high risk of active tuberculosis (TB) disease, but implementation is suboptimal. We investigated potential missed opportunities to identify and treat LTBI among HIV-positive patients accessing a large HIV outpatient service in London. Case records of all adult patients attending our service for HIV care diagnosed with active TB between 2011 and 2015 were reviewed to determine whether they met criteria for LTBI screening and whether screening was undertaken. Twenty-five patients were treated for TB. Of 15 (60%) patients who started TB treatment ≥6 months after HIV diagnosis, 14 (93%) met UK guideline-recommended criteria for LTBI screening and treatment; only one (7%) had been screened for LTBI. Eight of these 15 (53%) patients had additional risk factors for TB which are not reflected in current UK guidelines. Of 15 patients treated for TB ≥6 months after diagnosis of HIV, 14 (93%) had not been screened for LTBI, suggesting missed opportunities for TB prevention. People living with HIV may benefit from a broader approach to LTBI screening which takes into account additional recognised TB risk factors and ongoing TB exposure

Differential susceptibility of PCR reactions to inhibitors: an important and unrecognised phenomenon

PCR inhibition by nucleic acid extracts is a well known yet poorly described phenomenon. Inhibition assessment generally depends on the assumption that inhibitors affect all PCR reactions to the same extent; i.e. that the reaction of interest and the control reaction are equally susceptible to inhibition. To test this assumption we performed inhibition assessment on DNA extracts from human urine samples, fresh urine and EDTA using different PCR reactions

Predicting the knowledge–recklessness distinction in the human brain

Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria. We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those risks possessed by the participants. Our results provide neural evidence of a detectable difference in the mental state of knowledge in contrast to recklessness and suggest, as a proof of principle, the possibility of inferring from brain data in which legally relevant category a person belongs. Some potential legal implications of this result are discussed

Acetic Acid Enables Molecular Enumeration of Mycobacterium tuberculosis from Sputum and Eliminates the Need for a Biosafety Level 3 Laboratory

BACKGROUND: Improved monitoring of Mycobacterium tuberculosis response to treatment is urgently required. We previously developed the molecular bacterial load assay (MBLA), but it is challenging to integrate into the clinical diagnostic laboratory due to a labor-intensive protocol required at biosafety level 3 (BSL-3). A modified assay was needed. METHODS: The rapid enumeration and diagnostic for tuberculosis (READ-TB) assay was developed. Acetic acid was tested and compared to 4 M guanidine thiocyanate to be simultaneously bactericidal and preserve mycobacterial RNA. The extraction was based on silica column technology and incorporated low-cost reagents: 3 M sodium acetate and ethanol for the RNA extraction to replace phenol-chloroform. READ-TB was fully validated and compared directly to the MBLA using sputa collected from individuals with tuberculosis. RESULTS: Acetic acid was bactericidal to M. tuberculosis with no significant loss in 16S rRNA or an unprotected mRNA fragment when sputum was stored in acetic acid at 25°C for 2 weeks or -20°C for 1 year. This novel use of acetic acid allows processing of sputum for READ-TB at biosafety level 2 (BSL-2) on sample receipt. READ-TB is semiautomated and rapid. READ-TB correlated with the MBLA when 85 human sputum samples were directly compared (R2 = 0.74). CONCLUSIONS: READ-TB is an improved version of the MBLA and is available to be adopted by clinical microbiology laboratories as a tool for tuberculosis treatment monitoring. READ-TB will have a particular impact in low- and middle-income countries (LMICs) for laboratories with no BSL-3 laboratory and for clinical trials testing new combinations of anti-tuberculosis drugs

Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum.

INTRODUCTION: Resistance to second-line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. In the case presented here, successful WGS directly from sputum was achieved using targeted enrichment. CASE REPORT: A 29-year-old Nigerian woman was diagnosed with tuberculosis. Xpert MTB/RIF and Hain line probe assays identified rpoB and inhA mutations consistent with rifampicin and intermediate isoniazid resistance, and a further possible mutation conferring fluoroquinolone resistance. WGS directly from sputum identified a further inhA mutation consistent with high-level isoniazid resistance and confirmed the absence of fluoroquinolone resistance. Isoniazid was stopped, and the patient has completed 18 months of a fluoroquinolone-based regimen without relapse. DISCUSSION: Compared to rapid molecular tests (which can only examine a limited number of mutations) and WGS of culture isolates (which requires a culture step), WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common

Law and Neuroscience: Recommendations Submitted to the President\u27s Bioethics Commission

President Obama charged the Presidential Commission for the Study of Bioethical Issues to identify a set of core ethical standards in the neuroscience domain, including the appropriate use of neuroscience in the criminal-justice system. The Commission, in turn, called for comments and recommendations. The MacArthur Foundation Research Network on Law and Neuroscience submitted a consensus statement, published here, containing 16 specific recommendations. These are organized within three main themes: 1) what steps should be taken to enhance the capacity of the criminal justice system to make sound decisions regarding the admissibility and weight of neuroscientific evidence?; 2) to what extent can the capacity of neurotechnologies to aid in the administration of criminal justice be enhanced through research?; and 3) in what additional ways might important ethical issues at the intersection of neuroscience and criminal justice be addressed

Law and Neuroscience: Recommendations Submitted to the President\u27s Bioethics Commission

President Obama charged the Presidential Commission for the Study of Bioethical Issues to identify a set of core ethical standards in the neuroscience domain, including the appropriate use of neuroscience in the criminal-justice system. The Commission, in turn, called for comments and recommendations. The MacArthur Foundation Research Network on Law and Neuroscience submitted a consensus statement, published here, containing 16 specific recommendations. These are organized within three main themes: 1) what steps should be taken to enhance the capacity of the criminal justice system to make sound decisions regarding the admissibility and weight of neuroscientific evidence?; 2) to what extent can the capacity of neurotechnologies to aid in the administration of criminal justice be enhanced through research?; and 3) in what additional ways might important ethical issues at the intersection of neuroscience and criminal justice be addressed

G2i Knowledge Brief: A Knowledge Brief of the MacArthur Foundation Research Network on Law and Neuroscience

Courts are daily confronted with admissibility issues – such as in cases involving neuroscientific testimony – that sometimes involve both the existence of a general phenomenon (i.e., “G”) and the question of whether a particular case represents a specific instance of that general phenomenon (i.e., “i”). Unfortunately, courts have yet to carefully consider the implications of “G2i” for their admissibility decisions. In some areas, courts limit an expert’s testimony to the general phenomenon. They insist that whether the case at hand is an instance of that phenomenon is exclusively a jury question, and thus not an appropriate subject of expert opinion. In other cases, in contrast, courts hold that expert evidence must be provided on both the group-data issue (i.e., that the phenomenon exists) and what is called the “diagnostic” issue (i.e., that this case is an instance of that phenomenon). Consequently, the MacArthur Foundation Research Network on Law and Neuroscience has prepared this knowledge brief to help courts manage the G2i divide. Specifically, we recommend that courts first determine whether proffered expert testimony concerns only the existence of the general phenomenon or instead concerns both that and the diagnosis that a particular case represents an instance of that phenomenon. Only after making that determination should the court make its admissibility decision (guided, for instance, by the Daubert factors for admitting scientific evidence)

Evaluation of Type-Specific Real-Time PCR Assays Using the LightCycler and J.B.A.I.D.S. for Detection of Adenoviruses in Species HAdV-C

Sporadically, HAdVs from species HAdV-C are detected in acute respiratory disease outbreaks. To rapidly type these viruses, we designed real-time PCR assays that detect and discriminate between adenovirus types HAdV-C1, -C2, -C5, and -C6. Sixteen clinical isolates from the California Department of Public Health were used to validate the new assays. Type-specific TaqMan real-time PCR assays were designed and used independently to successfully identify 16 representative specimens. The lower limit of detection for our LightCycler singleplex real-time PCR assays were calculated to be 100, 100, 100, and 50 genomic copies per reaction for HAdV-C1, HAdV-C2, HAdV-C5 and HAdV-C6, respectively. The results for the singleplex J.B.A.I.D.S. assays were similar. Our assays did not cross-react with other adenoviruses outside of species HAdV-C, respiratory syncytial virus, influenza, or respiratory disease causing bacteria. These assays have the potential to be useful as diagnostic tools for species HAdV-C infection

Antimicrobial resistance in dairy slurry tanks: A critical point for measurement and control

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