Hepatotoxicity and tuberculosis treatment outcomes in chronic liver disease.

Background: The treatment of tuberculosis (TB) is known to cause liver injury, however, there is limited data to guide optimal treatment for patients with chronic liver disease. Methods: We undertook a retrospective case series of patients with chronic liver disease and TB disease. The primary objective was to determine if there was a difference in the incidence of drug-induced liver injury (DILI) in patients with cirrhosis versus those with chronic hepatitis. Additionally, we sought to compare TB treatment outcomes, type and duration of therapy, and incidence of adverse events. Results: We included 56 patients (chronic hepatitis 40; cirrhosis 16). There were 33 patients (58.9%) who experienced DILI requiring treatment modification, with no significant difference between groups (65% versus 43.8%, p = 0.23). Patients with chronic hepatitis were more likely to receive treatment with standard first-line intensive phase therapy that included a combination of rifampin (RIF), isoniazid, and pyrazinamide (80.8% versus 19.2%, p = 0.03) and any regimen than included isoniazid (92.5% versus 68.8%, p = 0.04). The risk of DILI was higher when more hepatotoxic TB medications were used. Overall treatment success in this cohort was low (55.4%), with no significant difference between groups (62.5% versus 37.5%, p = 0.14). Most patients with treatment success (97%) were able to tolerate a rifamycin. Conclusions: The risk of DILI is high, especially with the use of isoniazid, in patients with TB and chronic liver disease. This risk can be effectively mitigated with no difference in treatment outcomes in the presence of cirrhosis.

Historique: Il est bien connu que le traitement de la tuberculose (TB) provoque des lésions hépatiques, mais les données sont limitées pour orienter le traitement des patients atteints d'une hépatopathie chronique. Méthodologie: Les chercheurs ont étudié une série rétrospective de cas de patients atteints d'une hépathopathie chronique et d'une TB. Ils s'étaient donné comme objectif primaire de déterminer s'il y avait une différence entre l'incidence de lésion hépatique d'origine médicamenteuse (LHOM) chez les patients atteints d'une cirrhose et ceux atteints d'une hépatite chronique. De plus, ils ont comparé les résultats des traitements de la TB, le type et la durée du traitement et l'incidence d'événements indésirables. Résultats: Les chercheurs ont inclus 56 patients (hépatite chronique : 40; cirrhose : 16). De ce nombre, 33 (58,9 %) avaient présenté une LHOM ayant suscité une modification au traitement, sans différence notable entre les groupes : 65 % par rapport à 43,8 %, p = 0,23. Les patients atteints d'hépatite chronique étaient plus susceptibles de recevoir un traitement intensif standard en première ligne qui incluait une combinaison de rifampine (RIF), d'isoniazide et de pyrazinamide (80,8 % par rapport à 19,2 %, p = 0,03) ou une posologie qui comprenait de l'isoniazide (92,5 % par rapport à 68,8 %, p = 0,04). Le risque de LHOM était plus élevé lors de l'utilisation de médicaments contre la TB plus hépatotoxiques. La réussite globale du traitement était faible au sein de cette cohorte (55,4 %) et n'entraînait pas de différence significative entre les groupes (62,5 % par rapport à 37,5 %, p = 0,14). La plupart des patients dont le traitement était efficace (97 %) toléraient la rifamycine. Conclusions: Le risque de LHOM est élevé chez les patients atteints de TB et d'hépatopathie chronique, particulièrement lors de l'utilisation d'isoniazide. En présence de cirrhose, il est possible de l'atténuer avec efficacité sans modifier l'issue du traitement.

AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.

Bcl-2 and Mcl-1 proteins play a role in multiple myeloma (MM) cell survival, for which targeted inhibitors are being developed. AT-101 is an oral drug, which disrupts Bcl-2 and Mcl-1 function, impedes mitochondrial bioenergetic processes and induces apoptosis in MM cells. When combined with lenalidomide and dexamethasone (Rd), AT-101 significantly reduced tumor burden in an in vivo xenograft model of MM. These data provided rationale for a phase I/II study to establish the effective dose of AT-101 in combination with Rd (ARd regimen) in relapsed/refractory MM. A total of 10 patients were enrolled, most with high-risk cytogenetics (80%) and prior stem cell transplant (70%). Three patients were lenalidomide-refractory, 2 were bortezomib-refractory and 3 were daratumumab-refractory. The ARd combination was well tolerated with most common grade 3/4 adverse events being cytopenia's. The overall response rate was 40% and clinical benefit rate was 90%. The median progression free survival was 14.9 months (95% CI 7.1-NE). Patients responsive to ARd showed a decrease in Bcl-2:Bim or Mcl-1:Noxa protein complexes, increased CD8+ T and NK cells and depletion of T and B-regulatory cells. The ARd regimen demonstrated an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM prompting further investigation in additional patients.

The Struggle to End a Millennia-Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis.

This article provides an encompassing review of the current pipeline of putative and developed treatments for tuberculosis, including multidrug-resistant strains. The review has organized each compound according to its site of activity. To provide context, mention of drugs within current recommended treatment regimens is made, thereafter followed by discussion on recently developed and upcoming molecules at established and novel targets. The review is designed to provide a clinically applicable understanding of the compounds that are deemed most currently relevant, including those already under clinical study and those that have shown promising pre-clinical results. An extensive review of the efficacy and safety data for key contemporary drugs already incorporated into treatment regimens, such as bedaquiline, pretomanid, and linezolid, is provided. The three levels of the bacterial cell wall (mycolic acid, arabinogalactan, and peptidoglycan layers) are highlighted and important compounds designed to target each layer are delineated. Amongst others, the highly optimistic and potent anti-mycobacterial activity of agents such as BTZ-043, PBTZ 169, and OPC-167832 are emphasized. The evolving spectrum of oxazolidinones, such as sutezolid, delpazolid, and TBI-223, all aiming to exceed the efficacy achieved with linezolid yet offer a safer alternative to the potential toxicity, are reviewed. New and exciting prospective agents with novel mechanisms of impact against TB, including 3-aminomethyl benzoxaboroles and telacebec, are underscored. We describe new diaryloquinolines in development, striving to build on the immense success of bedaquiline. Finally, we discuss some of these compounds that have shown encouraging additive or synergistic benefit when used in combination, providing some promise for the future in treating this ancient scourge.

Exposure to lead-free frangible firing emissions containing copper and ultrafine particulates leads to increased oxidative stress in firing range instructors.

BACKGROUND: Since the introduction of copper based, lead-free frangible (LFF) ammunition to Air Force small arms firing ranges, instructors have reported symptoms including chest tightness, respiratory irritation, and metallic taste. These symptoms have been reported despite measurements determining that instructor exposure does not exceed established occupational exposure limits (OELs). The disconnect between reported symptoms and exposure limits may be due to a limited understanding of LFF firing byproducts and subsequent health effects. A comprehensive characterization of exposure to instructors was completed, including ventilation system evaluation, personal monitoring, symptom tracking, and biomarker analysis, at both a partially enclosed and fully enclosed range. RESULTS: Instructors reported symptoms more frequently after M4 rifle classes compared to classes firing only the M9 pistol. Ventilation measurements demonstrated that airflow velocities at the firing line were highly variable and often outside established standards at both ranges. Personal breathing zone air monitoring showed exposure to carbon monoxide, ultrafine particulate, and metals. In general, exposure to instructors was higher at the partially enclosed range compared to the fully enclosed range. Copper measured in the breathing zone of instructors, on rare occasions, approached OELs for copper fume (0.1 mg/m3). Peak carbon monoxide concentrations were 4-5 times higher at the partially enclosed range compared to the enclosed range and occasionally exceeded the ceiling limit (125 ppm). Biological monitoring showed that lung function was maintained in instructors despite respiratory symptoms. However, urinary oxidative stress biomarkers and urinary copper measurements were increased in instructors compared to control groups. CONCLUSIONS: Consistent with prior work, this study demonstrates that symptoms still occurred despite exposures below OELs. Routine monitoring of symptoms, urinary metals, and oxidative stress biomarkers can help identify instructors who are particularly affected by exposures. These results can assist in guiding protective measures to reduce exposure and protect instructor health. Further, a longitudinal study is needed to determine the long-term health consequences of LFF firing emissions exposure.

Time to Positive Culture Detection Predicts Mycobacterium avium Pulmonary Disease Severity and Treatment Initiation.

Rationale: Additional biomarkers are needed to guide initiation of treatment for Mycobacterium avium pulmonary disease (Mav-PD). Time to positive sputum culture detection (TTP) may offer potential prognostic and monitoring value. Objectives: To determine whether TTP is associated with infection severity and early treatment response in Mav-PD. Methods: We undertook a retrospective cohort study of patients with two or more sputum cultures positive for M. avium, an "index" sputum M. avium isolate during 2015-2019, a computed tomographic scan within 6 months, and no treatment for at least 6 months before index sputum. TTP was estimated from the date of laboratory receipt of the specimen to the date of culture positivity confirmation. TTP was tested for association with markers of infection severity (Mav-PD, bronchiectasis, cavitary disease, treatment initiation by 3 and 6 months, and acid fast bacilli [AFB] smear) and treatment response using Mann-Whitney U, Spearman's correlation coefficient, and Wilcoxon signed-rank tests. We explored a threshold TTP that could identify significant M. avium disease. Results: We included 125 patients with mean (standard deviation) age 68.5 (12.5) years and 65% fulfilled disease criteria. Median TTP was 12 (interquartile range 10-15; range 6-44) days. TTP and AFB smear grade were negatively correlated (ρ -0.58; P < 0.001). TTP was associated with nontuberculous mycobacteria (NTM) disease (P = 0.03), AFB smear positivity (P < 0.001), and treatment initiation by 3 (P = 0.01) and 6 (P = 0.03) months. A threshold TTP of 10 days or less was associated with Mav-PD (80.6% vs. 58.4%; ð [95% confidence interval (CI)] 22.1% [5.6-38.6%]; P = 0.02), AFB smear positivity (83.3% vs. 20.2%, ð [95% CI] 63.1% [48.3-77.9%]; P < 0.001), treatment by 3 (38.9% vs. 13.5%; ð [95% CI] 25.4% [8.0-42.8%]; P = 0.003) and 6 (47.2% vs. 19.1%; ð [95% CI] 28.1% [9.9-46.4%]; P = 0.003) months. After 3 and 6 months of treatment, the median (interquartile range) change in TTP was 8 (1 undefined; P < 0.001) and 7 (0 undefined; P = 0.001) days, respectively. Conclusions: TTP is associated with bacterial burden and infection severity and increases in response to treatment. A threshold of 10 days or less may be useful in predicting significant Mav-PD. As a readily available biomarker, further exploration of TTP is imperative.

Lymphocutaneous spread of Mycobacterium elephantis in an immunocompetent individual: A case report.

Mycobacterium elephantis was first described when isolated from an elephant that succumbed to lung abscess. However, despite this namesake, it is not associated with animals and has been described most often as a probable colonizer rather than pathogen in humans with chronic lung disease. In this report, we describe the first case of lymphocutaneous infection from M. elephantis, likely as a result of cutaneous inoculation with contaminated soil. This offers further evidence to its capabilities as a pathogen. We provide a review of the limited prior reports of M. elephantis and outline the available in vitro data on efficacy of various antimycobacterial agents.

Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial.

BACKGROUND: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. METHODS: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. RESULTS: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. INTERPRETATION: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04329611.

Rifampin-resistant/multidrug-resistant Tuberculosis in Alberta, Canada: Epidemiology and treatment outcomes in a low-incidence setting.

Treatment of rifampin-monoresistant/multidrug-resistant Tuberculosis (RR/MDR-TB) requires long treatment courses, complicated by frequent adverse events and low success rates. Incidence of RR/MDR-TB in Canada is low and treatment practices are variable due to the infrequent experience and challenges with drug access. We undertook a retrospective cohort study of all RR/MDR-TB cases in Alberta, Canada from 2007-2017 to explore the epidemiology and outcomes in our low incidence setting. We performed a descriptive analysis of the epidemiology, treatment regimens and associated outcomes, calculating differences in continuous and discrete variables using Student's t and Chi-squared tests, respectively. We identified 24 patients with RR/MDR-TB. All patients were foreign-born with the median time to presentation after immigration being 3 years. Prior treatment was reported in 46%. Treatment was individualized. All patients achieved sputum culture conversion within two months of treatment initiation. The median treatment duration after culture conversion was 18 months (IQR: 15-19). The mean number of drugs utilized during the intensive phase was 4.3 (SD: 0.8) and during the continuation phase was 3.3 (SD: 0.9) and the mean adherence to medications was 95%. Six patients completed national guideline-concordant therapy, with many patients developing adverse events (79%). Treatment success (defined as completion of prescribed therapy or cure) was achieved in 23/24 patients and no acquired drug resistance or relapse was detected over 1.8 years of median follow-up. Many cases were captured upon immigration assessment, representing important prevention of community spread. Despite high rates of adverse events and short treatment compared to international guidelines, success in our cohort was very high at 96%. This is likely due to individualization of therapy, frequent use of medications with high effectiveness, intensive treatment support, and early sputum conversion seen in our cohort. There should be ongoing exploration of treatment shortening with well-tolerated, efficacious oral agents to help patients achieve treatment completion.

Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown. METHODS: We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982-2001 and 2002-2019. The proportion of MDR tuberculosis among migrants arriving from high MDR (HMDR) tuberculosis burden countries during these 2 periods was used to estimate the proportion of cases due to immigration versus change in proportion in the country of birth. Epidemiologic, spatiotemporal, and drug resistance pattern data were used to confirm local transmission. RESULTS: Fifty-two of 3514 (1.48%) foreign-born culture-positive tuberculosis patients had MDR tuberculosis: 8 (0.6%) in 1982-2001 and 44 (2.0%) in 2002-2019. Between time periods, the proportion of MDR tuberculosis among migrants with tuberculosis from HMDR tuberculosis countries increased from 1.11% to 3.62%, P = .003; 31.6% attributable to recent immigration and 68.4% to a higher proportion of MDR tuberculosis in cases arrived from HMDR tuberculosis countries. No cases of MDR tuberculosis were attributable to local transmission. CONCLUSIONS: In stark contrast to HMDR tuberculosis countries, local transmission plays no important role in the occurrence of MDR tuberculosis in Canada. Improved tuberculosis programming in HMDR tuberculosis countries is urgently needed.

Clinical characteristics and outcomes for paediatric patients admitted with congenital or acquired syphilis: a population-based cohort study.

OBJECTIVES: Paediatric congenital and acquired syphilis cases have been increasing since 2012 in the USA. Potential differences in associated hospitalisation trends and healthcare utilisation between the two syphilis entities have not yet been assessed. We sought to compare these entities and describe their clinical characteristics, distribution and impact in the USA. METHODS: We conducted a population-based cohort study using the 2016 Kids' Inpatient Database (KID) to identify and characterise syphilis-associated hospitalisations among paediatric patients (age 0-21 years) in the USA during the year of 2016. Length of stay and hospitalisation costs for patients with congenital and acquired syphilis were compared in multivariable models. RESULTS: A total of 1226 hospitalisations with the diagnosis of syphilis were identified. Of these patients, 958 had congenital syphilis and 268 were acquired cases. The mean cost of care for congenital syphilis was $23 644 (SD=1727), while the treatment of a patient with acquired syphilis on average cost $10 749 (SD=1966). Mean length of stay was 8 days greater and mean total costs were $12 895 (US dollars) higher in the congenital syphilis cohort compared with the acquired syphilis cohort. In congenital syphilis, there were greater frequency of cases in the Southern and Western regions of the USA (p<0.001). CONCLUSION: Congenital syphilis was associated with greater healthcare-related expenditure than acquired syphilis in paediatric patients. In addition to improving patient outcomes, congenital syphilis prevention efforts may significantly reduce healthcare utilisation burden and cost.

Epidemiology of E. coli in Cystic Fibrosis Airways Demonstrates the Capacity for Persistent Infection but Not Patient-Patient Transmission.

Escherichia coli is frequently isolated from the respiratory secretions of cystic fibrosis (CF) patients yet is not considered a classical CF pathogen. Accordingly, little is known about the natural history of this organism in the CF airways, as well as the potential for patient-to-patient transmission. Patients attending the Calgary Adult CF Clinic (CACFC) between January 1983 and December 2016 with at least one E. coli-positive sputum culture were identified by retrospective review. Annual E. coli isolates from the CACFC biobank from each patient were typed by pulsed-field gel electrophoresis (PFGE) and isolates belonging to shared pulsotypes were sequenced. Single nucleotide polymorphism (SNP) and phylogenetic analysis were used to investigate the natural history of E. coli infection and identify potential transmission events. Forty-five patients with E. coli-positive sputum cultures were identified. Most patients had a single infection episode with a single pulsotype, while replacement of an initial pulsotype with a second was observed in three patients. Twenty-four had E. coli recovered from their sputum more than once and 18 patients had persistent infections (E. coli carriage >6 months with ≥3 positive cultures). Shared pulsotypes corresponded to known extraintestinal pathogenic E. coli strains: ST-131, ST-73, and ST-1193. Phylogenetic relationships and SNP distances among isolates within shared pulsotypes were consistent with independent acquisition of E. coli by individual patients. Most recent common ancestor date estimates of isolates between patients were inconsistent with patient-to-patient transmission. E. coli infection in CF is a dynamic process that appears to be characterized by independent acquisition within our patient population and carriage of unique sets of strains over time by individual patients.

Incidence, treatment, and outcomes of isoniazid mono-resistant Mycobacterium tuberculosis infections in Alberta, Canada from 2007-2017.

Isoniazid resistant Mycobacterium tuberculosis (Hr-TB) is the most frequently encountered TB resistance phenotype in North America but limited data exist on the effectiveness of current therapeutic regimens. Ineffective treatment of Hr-TB increases patient relapse and anti-mycobacterial resistance, specifically MDR-TB. We undertook a multi-centre, retrospective review of culture-positive Hr-TB patients in Alberta, Canada (2007-2017). We assessed incidence and treatment outcomes, with a focus on fluoroquinolone (FQ)-containing regimens, to understand the risk of unsuccessful outcomes. Rates of Hr-TB were determined using the mid-year provincial population and odds of unsuccessful treatment was calculated using a Fisher's Exact test. One hundred eight patients of median age 37 years (IQR: 26-50) were identified with Hr-TB (6.3%), 98 of whom were able to be analyzed. Seven percent reported prior treatment. Rate of foreign birth was high (95%), but continent of origin did not predict Hr-TB (p = 0.47). Mean compliance was 95% with no difference between FQ and non-FQ regimens (p = 1.00). Treatment success was high (91.8%). FQ-containing regimens were frequently initiated (70%), with no difference in unsuccessful outcomes compared to non-FQ-containing regimens (5.8% vs. 13.8%, OR 0.4, 95% CI 0.1-2.3, p = 0.23). Only one patient (1%) utilizing a less common non-FQ-based regimen including two months of pyrazinamide developed secondary multidrug resistance. Unsuccessful treatment was low (<10%) relative to comparable literature (~15%) and showed similar outcomes for FQ and non-FQ-based regimens and no deficit to those using intermittent fluoroquinolones in the continuation phase of treatment. Our findings are similar to recent data, however prospective, randomized trials of adequate power are needed to determine the optimal treatment for Hr-TB.

Asymmetric eye size in an infant.

Toxoplasmosis is an uncommon congenital infection in Canada, but one with potentially severe clinical manifestations, including fetal death. Neurologic and ocular manifestations are frequent in untreated disease; however, small eye size (microphthalmia) is a rare finding. This finding may be a marker of severe ocular disease. As universal screening does not occur in Canada, clinicians' early recognition is imperative, particularly given the lack of risk factors in many patients and the benefit that treatment may have even in initially asymptomatic disease. Here, we report a case of congenital toxoplasmosis and review the diagnostics and treatment of the infection.

La toxoplasmose est une infection congénitale rare au Canada, mais au potentiel de manifestations cliniques graves, y compris la mort fœtale. Les manifestations neurologiques et oculaires sont fréquentes lorsque la maladie n'est pas traitée, et dans de rares cas, on remarque des globes oculaires de petite dimension (microphtalmie). Cette observation peut être un marqueur de maladie oculaire grave. Il n'y a pas de dépistage universel au Canada, mais il est impératif que les cliniciens reconnaissent rapidement la maladie, notamment en raison de l'absence de facteurs de risque chez de nombreux patients et des avantages potentiels des traitements lorsque la maladie est d'abord asymptomatique. Les auteurs déclarent un cas de toxoplasmose congénitale et analysent les diagnostics et le traitement de l'infection.

PHArmacists' perspective oN the Take hOme naloxone prograM (The PHANTOM Study).

OBJECTIVE: To evaluate pharmacists' attitudes toward the Take Home Naloxone (THN) program and identify areas that could be improved to support pharmacists' involvement. METHODS: Pharmacists on the Alberta College of Pharmacists' directory were invited to complete an online survey between July 10 and August 8, 2016. The survey consisted of 19 questions. Descriptive statistics were used to analyze the data. RESULTS: Four hundred seventy pharmacists completed the survey (response rate = 11.2%). A total of 76.8% of respondents strongly agreed or agreed that pharmacists should be screening patients to identify those at risk of opioid overdose. Full-time pharmacists were more likely to agree (p = 0.02). A total of 79.8% of respondents strongly agreed or agreed that pharmacists should be recommending THN kits. Pharmacists working in large population centres (p = 0.008) and full-time pharmacists (p = 0.02) were more likely to agree with this statement. Furthermore, 60.6% of pharmacists were extremely willing or very willing to participate in the THN program. Pharmacists in practice for ≤15 years were more willing to participate in the THN program than pharmacists in practice >15 years (p = 0.03). The most common perceived barriers to implementation of the THN program were lack of time in pharmacists' current work environment and education about the program. CONCLUSIONS: Overall, pharmacists had positive attitudes toward screening patients to identify those at risk of opioid overdose, recommending THN kits and willingness to participate in the program. Factors that may facilitate increased participation in the program include addressing time issues and improving education about the THN program.

A transatlantic perspective on 20 emerging issues in biological engineering.

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

Prosthetic joint and implant contamination caused by Ralstonia pickettii: a report of three casesÙ­.

We describe three cases of orthopaedic contamination caused by Ralstonia pickettii grown from prosthetic joint and implant material cultures following sonication in the microbiology laboratory. Given the temporal association between the cases, lack of clinical or intra-operative features of infection, growth of the organism in the water bath, and unlikely etiology of Ralstonia as a prosthetic joint or implant pathogen, the bacteria were judged to be contaminants.

[Not Available]. / Abordando la problemática de las armas biológicas en el siglo XXI: el papel de una red de prevención 2.0.

The strategic use of disease in warfare has long proven a menace to humankind; however, the changing nature of both science and security has the potential to encourage the assimilation of new (and old) biological weapons. This short article begins by outlining some of these changes before considering the means and measures in place to deal with the challenge of biological weapons. It proceeds to outline a Web of Prevention 2.0, comprised of mutually reinforcing strands that are intended to form a framework for a more holistic approach to dealing with the challenge of biological weapons around the globe in the 21st century.

From cases to capacity? A critical reflection on the role of 'ethical dilemmas' in the development of dual-use governance.

The dual-use issue is often framed as a series of paralyzing 'dilemmas' facing the scientific community as well as institutions which support innovation. While this conceptualization of the dual-use issue can be useful in certain contexts (such as in awareness-raising and as part of educational activities directed at the scientific community) its usefulness is more limited when reflecting on the governance and politics of the dual-use issue. Within this paper, key shortcomings of the dilemma framing are outlined. It is argued that many of the issues raised in the most recent debates about 'dual-use' bird flu research remain unresolved. This includes questions about the trajectories of certain lines of research, as well as broader trends in the practice and governance of science. This leads to difficult questions about current approaches to the dual-use issue within the US, as well as internationally.