Microbial sensor variation across biogeochemical conditions in the terrestrial deep subsurface.

Microbes can be found in abundance many kilometers underground. While microbial metabolic capabilities have been examined across different geochemical settings, it remains unclear how changes in subsurface niches affect microbial needs to sense and respond to their environment. To address this question, we examined how microbial extracellular sensor systems vary with environmental conditions across metagenomes at different Deep Mine Microbial Observatory (DeMMO) subsurface sites. Because two-component systems (TCSs) directly sense extracellular conditions and convert this information into intracellular biochemical responses, we expected that this sensor family would vary across isolated oligotrophic subterranean environments that differ in abiotic and biotic conditions. TCSs were found at all six subsurface sites, the service water control, and the surface site, with an average of 0.88 sensor histidine kinases (HKs) per 100 genes across all sites. Abundance was greater in subsurface fracture fluids compared with surface-derived fluids, and candidate phyla radiation (CPR) bacteria presented the lowest HK frequencies. Measures of microbial diversity, such as the Shannon diversity index, revealed that HK abundance is inversely correlated with microbial diversity (r2 = 0.81). Among the geochemical parameters measured, HK frequency correlated most strongly with variance in dissolved organic carbon (r2 = 0.82). Taken together, these results implicate the abiotic and biotic properties of an ecological niche as drivers of sensor needs, and they suggest that microbes in environments with large fluctuations in organic nutrients (e.g., lacustrine, terrestrial, and coastal ecosystems) may require greater TCS diversity than ecosystems with low nutrients (e.g., open ocean).IMPORTANCEThe ability to detect extracellular environmental conditions is a fundamental property of all life forms. Because microbial two-component sensor systems convert information about extracellular conditions into biochemical information that controls their behaviors, we evaluated how two-component sensor systems evolved within the deep Earth across multiple sites where abiotic and biotic properties vary. We show that these sensor systems remain abundant in microbial consortia at all subterranean sampling sites and observe correlations between sensor system abundances and abiotic (dissolved organic carbon variation) and biotic (consortia diversity) properties. These results suggest that multiple environmental properties may drive sensor protein evolution and highlight the need for further studies of metagenomic and geochemical data in parallel to understand the drivers of microbial sensor evolution.

Negative mpMRI Rules Out Extra-Prostatic Extension in Prostate Cancer before Robot-Assisted Radical Prostatectomy.

Background: The accuracy of multi-parametric MRI (mpMRI) in the pre-operative staging of prostate cancer (PCa) remains controversial. Objective: The purpose of this study was to evaluate the ability of mpMRI to accurately predict PCa extra-prostatic extension (EPE) on a side-specific basis using a risk-stratified 5-point Likert scale. This study also aimed to assess the influence of mpMRI scan quality on diagnostic accuracy. Patients and Methods: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre. Three radiologists retrospectively reviewed mpMRI blinded to RP pathology and assigned a Likert score (1-5) for EPE on each side of the prostate. Each scan was also ascribed a Prostate Imaging Quality (PI-QUAL) score for assessing the quality of the mpMRI scan, where 1 represents the poorest and 5 represents the best diagnostic quality. Outcome measurements and statistical analyses: Diagnostic performance is presented for the binary classification of EPE, including 95% confidence intervals and the area under the receiver operating characteristic curve (AUC). Results: A total of 231 lobes from 121 men (mean age 56.9 years) were evaluated. Of these, 39 men (32.2%), or 43 lobes (18.6%), had EPE. A Likert score ≥3 had a sensitivity (SE), specificity (SP), NPV, and PPV of 90.4%, 52.3%, 96%, and 29.9%, respectively, and the AUC was 0.82 (95% CI: 0.77-0.86). The AUC was 0.76 (95% CI: 0.64-0.88), 0.78 (0.72-0.84), and 0.92 (0.88-0.96) for biparametric scans, PI-QUAL 1-3, and PI-QUAL 4-5 scans, respectively. Conclusions: MRI can be used effectively by genitourinary radiologists to rule out EPE and help inform surgical planning for men undergoing RARP. EPE prediction was more reliable when the MRI scan was (a) multi-parametric and (b) of a higher image quality according to the PI-QUAL scoring system.

Universal Anesthesia Machine: Clinical Application in an Austere, Resource-Limited Environment.

INTRODUCTION: In austere environments, the safe administration of anesthesia becomes challenging because of unreliable electrical sources, limited amounts of compressed gas, and insufficient machine maintenance capabilities. Such austere environments exist in battlefield medicine, in low- and middle-income countries (LMICs), and in areas struck by natural disasters. Whether in military operations or civilian settings, the Universal Anesthesia Machine (UAM) (Gradian Health Systems, New York, New York) is a draw-over device capable of providing safe and effective general anesthesia when external oxygen supplies or reliable electrical sources are limited. This brief report discusses a proof-of-concept observational study demonstrating the clinical utility of the UAM in a resource-limited area. MATERIALS AND METHODS: This observational study of 20 patients in Haiti who underwent general anesthesia using the UAM highlights the device's capability to deliver anesthesia intraoperatively in a resource-limited LMIC clinical setting. Preoxygenation was achieved with the UAM's draw-over oxygen supply. Patients received acetaminophen for analgesia, dexmedetomidine for preinduction anesthesia, and succinylcholine for paralysis. After induction, the UAM provided a mixture of oxygen and isoflurane for maintenance of anesthesia. Manual ventilation was performed using draw-over bellows until spontaneous ventilation recurred, when clinically appropriate, artificial airways were removed. Intraoperative medication was administered at the anesthesiologist's discretion. The institutional review board at the U.S. anesthesiologists' affiliated institution and the Haitian hospital approved this study; patients were consented in their native language. RESULTS: Two anesthesiologists used the UAM to deliver general anesthesia to 20 patients in a Haitian hospital without access to an external oxygen supply, reliable power grid, or opioids. The patients' average age was ~40 years, and 90% of them were male. Most of the cases were herniorrhaphy (50%) and hydrocelectomy (25%) surgeries. The median American Society of Anesthesiologists (ASA) score was 2; 45% of the patients had an ASA score of 1, and none had an ASA score >3. Of the 20 cases, 55% of patients received an endotracheal tube, and 40% received a laryngeal mask airway; for one patient, only a masked airway was used. Every patient was discharged on the day of the surgery. No complications occurred in the perioperative or 1-month follow-up period. CONCLUSION: The UAM can be used where a lack of resources and training exist because of its simple design, built-in oxygen concentrator, and capacity to revert from continuous-flow to draw-over anesthesia in the event of a power failure or if external oxygen supplies are unavailable. We believe the UAM addresses some of the shortcomings of modern anesthesia machines and has the potential to improve the delivery of safe general anesthesia in combat and austere scenarios. Further studies could consider different types of surgeries than those reported here and involve more complex patients. Studies involving alternative anesthetic agents and non-anesthesiologist personnel are also needed. Overall, this brief report detailing the use of the UAM following a natural disaster in a LMIC is proof of concept that the machine can provide reliable anesthesia for surgical procedures in austere and resource-limited environments, including disaster areas and modern combat zones.

Corporate medical cultures: MD Anderson as a case study in American corporate medical values.

This paper contributes to the evolving body of literature diagnosing the 'business-like' transformation of American medicine by historicising and recuperating the concepts of medical leadership and the corporation. In an analysis of the evolving uses of 'leadership' in medical literature, we argue that the term's appeal derives from its ability to productively articulate the inevitable conflicts that arise between competing values in corporations, and so should be understood as a response to the neoliberal corporation's false resolutions of conflict according to the single value of profit (or consumer welfare for the business-like non-profit). Drawing on mid-century theories of the corporation to reframe dominant social histories of medical corporatisation, we go on to argue that large medical institutions are productive sites for deliberation over the medical profession's social contract. Our primary case study for this longer historical and broader theoretical argument is the MD Anderson Cancer Center, the world's foremost treatment hospital for patients with cancer. We hold that the historical trajectory that led to MD Anderson's exceptional but exemplary place in the evolution of American corporate medicine is reflective of historical trends in the practice.

Random access in large-scale DNA data storage.

Synthetic DNA is durable and can encode digital data with high density, making it an attractive medium for data storage. However, recovering stored data on a large-scale currently requires all the DNA in a pool to be sequenced, even if only a subset of the information needs to be extracted. Here, we encode and store 35 distinct files (over 200 MB of data), in more than 13 million DNA oligonucleotides, and show that we can recover each file individually and with no errors, using a random access approach. We design and validate a large library of primers that enable individual recovery of all files stored within the DNA. We also develop an algorithm that greatly reduces the sequencing read coverage required for error-free decoding by maximizing information from all sequence reads. These advances demonstrate a viable, large-scale system for DNA data storage and retrieval.

Mindfulness of voices, self-compassion, and secure attachment in relation to the experience of hearing voices.

OBJECTIVES: Developing compassion towards oneself has been linked to improvement in many areas of psychological well-being, including psychosis. Furthermore, developing a non-judgemental, accepting way of relating to voices is associated with lower levels of distress for people who hear voices. These factors have also been associated with secure attachment. This study explores associations between the constructs of mindfulness of voices, self-compassion, and distress from hearing voices and how secure attachment style related to each of these variables. DESIGN: Cross-sectional online. METHOD: One hundred and twenty-eight people (73% female; Mage  = 37.5; 87.5% Caucasian) who currently hear voices completed the Self-Compassion Scale, Southampton Mindfulness of Voices Questionnaire, Relationships Questionnaire, and Hamilton Programme for Schizophrenia Voices Questionnaire. RESULTS: Results showed that mindfulness of voices mediated the relationship between self-compassion and severity of voices, and self-compassion mediated the relationship between mindfulness of voices and severity of voices. Self-compassion and mindfulness of voices were significantly positively correlated with each other and negatively correlated with distress and severity of voices. CONCLUSION: Mindful relation to voices and self-compassion are associated with reduced distress and severity of voices, which supports the proposed potential benefits of mindful relating to voices and self-compassion as therapeutic skills for people experiencing distress by voice hearing. PRACTITIONER POINTS: Greater self-compassion and mindfulness of voices were significantly associated with less distress from voices. These findings support theory underlining compassionate mind training. Mindfulness of voices mediated the relationship between self-compassion and distress from voices, indicating a synergistic relationship between the constructs. Although the current findings do not give a direction of causation, consideration is given to the potential impact of mindful and compassionate approaches to voices.

Delivery of cognitive-behaviour therapy for psychosis: a service user preference trial.

BACKGROUND: Clinical guidelines recommend cognitive behaviour therapy (CBT) for people with psychosis, however, implementation is poor and not everyone wishes to engage with therapy. Understanding service user (SU) preferences for receiving such treatments is a priority for services. AIMS: To explore SU preferences and outcomes of different methods of delivering CBT for psychosis. METHOD: SUs experiencing psychosis could choose between treatment as usual (TAU); TAU plus telephone-delivered CBT with self-help, CBT recovery manual (TS); high support CBT (HS - TAU plus TS plus group sessions) or randomisation. Participants received their option of choice and were followed-up on several outcomes over 9 and 15 months. RESULTS: Of 89 people recruited, three chose to be randomised and 86 expressed a treatment preference (32 chose TAU, 34 chose TS, 23 chose HS). There were few differences between those who chose therapy compared to those who chose TAU. Those who had more positive impacts from their symptoms were significantly more likely to choose TAU. CONCLUSIONS: Most people had strong preferences about treatment delivery and a substantial number did not wish to receive additional therapy. These findings have to be considered when planning and allocating resources for people with psychosis.

Travel health and pretravel preparation in the patient with inflammatory bowel disease.

BACKGROUND AND AIMS: Foreign travel for people with inflammatory bowel disease (IBD) carries an increased risk of travel-related morbidity. There is limited research looking specifically at travel-associated health risks and travel preparation in patients with IBD. The aims of this study are to explore the experience of travel, pretravel preparation undertaken by the patient with IBD and examine IBD healthcare professionals' (HCP) confidence at providing travel advice and the content of that advice. METHODS: A survey of patients with IBD attending an outpatient clinic with a separate online survey sent to IBD HCPs recruited using regional and international network databases. RESULTS: A total of 132 patients with IBD, Crohn's disease (67/132, 51%), male (60/132, 45%) and 128 HCPs (IBD nurse specialist 113, 88%; IBD physician 15, 12%) completed the questionnaires. IBD affected travel to some extent in 62% (82/132) of patients, and 64% (84/132) had experienced an IBD flare, of whom 64% still travelled overseas during this time. Only 23% (31/132) travellers sought pretravel medical advice and 40% (53/132) obtained travel insurance. Forty-eight per cent of respondents on immunomodulator therapy were unaware of the need to avoid live vaccines. Twenty-seven per cent (34/128) of IBD HCPs are not confident at providing pretravel advice; vaccination advice (54%), obtaining travel insurance (61%) and healthcare abroad (78%) are the areas of most uncertainty. CONCLUSIONS: Patients do not seek adequate pretravel advice and consultations for those who do are often deficient. The majority of IBD professionals are not confident to provide comprehensive travel advice. Greater IBD-specific travel education and awareness is needed for both patients with IBD and professionals.

Barriers and facilitators to recruitment in mental health services: care coordinators' expectations and experience of referring to a psychosis research trial.

OBJECTIVE: High-quality research trials are necessary to provide evidence for the effective management of mental health difficulties, but successful recruitment can be challenging. DESIGN: This qualitative study examines the perceived barriers and facilitators to referring mental health service users to research trials. Seven care coordinators (n = 7) who facilitated the recruitment of participants to a cognitive behaviour therapy - informed psychosis intervention trial were interviewed. METHOD: Demographic information was collected by questionnaire and a semi-structured guide was used to explore barriers and facilitators to referring to a partially randomized participant preference trial. Qualitative data were thematically analysed. RESULTS: Four key themes, each with a number of sub-themes, were identified: (1) engage the care coordinator in the recruitment process, (2) barriers to referring to research studies, (3) facilitators to referring to research studies; (4) organisational constraints impact on implementing research outcomes into routine clinical practice. CONCLUSIONS: Understanding the barriers and facilitators to recruitment in mental health research could improve recruitment strategies. Our findings highlight the need for researchers' to closely consider their recruitment strategies as service users are not always given the choice to participate in research. Several key recommendations are made based on these findings in order to maximize successful recruitment to research studies. Overall, we recommend that researchers' adopt a flexible, tailor-made approach for each clinical team to ensure a collaborative relationship is developed between research staff and clinicians. PRACTITIONER POINTS: A qualitative approach to understanding recruitment challenges provides a useful opportunity to explore the barriers and facilitators to recruiting participants to research studies. These findings have practical implications that highlight the need for a collaborative partnership between researchers and clinical services. Understanding the challenges and issues related to recruitment can help researchers consider strategies to overcome recruitment issues. More research with a larger sample, across a broader population and in different mental health services is required.

Recovery-focused cognitive-behavioural therapy for recent-onset bipolar disorder: randomised controlled pilot trial.

BACKGROUND: Despite evidence for the effectiveness of structured psychological therapies for bipolar disorder no psychological interventions have been specifically designed to enhance personal recovery for individuals with recent-onset bipolar disorder. AIMS: A pilot study to assess the feasibility and effectiveness of a new intervention, recovery-focused cognitive-behavioural therapy (CBT), designed in collaboration with individuals with recent-onset bipolar disorder intended to improve clinical and personal recovery outcomes. METHOD: A single, blind randomised controlled trial compared treatment as usual (TAU) with recovery-focused CBT plus TAU (n = 67). RESULTS: Recruitment and follow-up rates within 10% of pre-planned targets to 12-month follow-up were achieved. An average of 14.15 h (s.d. = 4.21) of recovery-focused CBT were attended out of a potential maximum of 18 h. Compared with TAU, recovery-focused CBT significantly improved personal recovery up to 12-month follow-up (Bipolar Recovery Questionnaire mean score 310.87, 95% CI 75.00-546.74 (s.e. = 120.34), P = 0.010, d = 0.62) and increased time to any mood relapse during up to 15 months follow-up (χ2 = 7.64, P<0.006, estimated hazard ratio (HR) = 0.38, 95% CI 0.18-0.78). Groups did not differ with respect to medication adherence. CONCLUSIONS: Recovery-focused CBT seems promising with respect to feasibility and potential clinical effectiveness. Clinical- and cost-effectiveness now need to be reliably estimated in a definitive trial.

An exploration of the therapeutic alliance within a telephone-based cognitive behaviour therapy for individuals with experience of psychosis.

OBJECTIVES: This study investigated the therapeutic alliance (TA) between clients and therapists involved in a telephone-based cognitive behaviour therapy (CBT) oriented psychological intervention for individuals experiencing psychosis. DESIGN: The telephone intervention involved recovery-focused CBT with use of a self-help guide and group intervention co-facilitated by colleagues with personal experience of psychosis. It was delivered as part of a Participant Preference Trial. METHODS: Twenty-one client/therapist dyads were examined within this study. In addition to a measure of TA, clients completed measures of depression, social functioning, symptom severity, and strength of treatment preference, while therapists completed measures related to the level of shared formulation, therapist confidence, and therapeutic change estimates. RESULTS: Therapeutic alliance levels were comparable to previously reported face-to-face psychosis intervention studies. Clients consistently reported significantly higher TA ratings compared to therapists. Depression scores and the strength of preference for treatment were significantly associated with client TA. Greater therapist perceived change was associated with higher therapist rated TA, while higher numbers of missed therapy sessions associated with lower therapist ratings. CONCLUSIONS: Telephone-based psychosis interventions may support the formation of positive relationships that are comparable to the quality of relationships developed between therapists and clients during face-to-face CBT therapy. Methodological limitations including low participant numbers and heightened risk of a Type I error necessitate caution when interpreting findings. Further research into therapist and client variables associated with TA is required. PRACTITIONER POINTS: Telephone delivered interventions to support people with psychosis-related difficulties can result in the development of a good quality TA between therapists and clients. There is a significant difference between therapist and client ratings of TA. Clients tend to score the quality of the TA significantly more highly than therapists. Providing clients with choice when participating in therapeutic interventions could potentially contribute towards improved TA reporting by clients.

Assessing therapist adherence to recovery-focused cognitive behavioural therapy for psychosis delivered by telephone with support from a self-help guide: psychometric evaluations of a new fidelity scale.

BACKGROUND: Recent research has highlighted the importance of psychological interventions such as cognitive behavioural therapy (CBT) in improving outcomes and promoting recovery for people with experience of psychosis, although a lack of trained therapists means that availability of face-to-face CBT is low. Alternative modes of delivering CBT are being explored, such as telephone and self-help methods, although research to date on whether they can be implemented effectively is limited. AIMS: The aims of the present study were to describe and evaluate a new therapy fidelity scale (ROSTA; Recovery Oriented Self-help and Telephone therapy Adherence). This scale was developed to assess fidelity to cognitive behaviour therapy for psychosis (CBTp) focused on improving recovery, with optional subscales for delivery over the telephone and alongside a self-help guide. METHOD: Experienced CBT therapists rated recorded therapy sessions using the ROSTA scale. The scores were used to assess internal consistency and inter-rater reliability, before being compared to scores from an independent expert rater using an alternative fidelity scale for cognitive therapy in psychosis (the CTS-Psy), to investigate concurrent validity. RESULTS: The ROSTA scale demonstrated excellent internal consistency, inter-rater reliability and validity when evaluated as a whole, although findings were mixed in terms of the individual subscales and items. CONCLUSIONS: The ROSTA scale is, on the whole, a reliable and valid tool, which may be useful in training and supervision, a utility that would be further emphasized if the therapeutic intervention it assesses is deemed to be efficacious based on future work.

Informal caregivers in early psychosis: evaluation of need for psychosocial intervention and unresolved grief.

AIM: Relatives of service users involved with Early Intervention in Psychosis services often experience substantial distress and need associated with their role as caregivers. This study adapted versions of the relatives cardinal needs schedule and the Texas inventory of grief and tested their utility for use among relatives of service users experiencing a first episode of psychosis. METHODS: staff, service users and relatives were consulted and a pilot took place which facilitated the creation of the relatives' urgent needs schedule-early Intervention version (RUNS-EI) and the Texas inventory of grief-early Intervention version (TIG-EI). Thirty service user-caregiver dyads were recruited for the evaluation of reliability and validity. RESULTS: The level of 'urgent need' identified by the RUNS-EI demonstrated good concurrent validity with measures of service user social and global functioning as well as measures assessing relatives' distress, expressed emotion and grief. The measure demonstrated acceptable interrater and test-retest reliability. The profile of need is reported. The TIG-EI demonstrated 'excellent' internal consistency. It also demonstrated good concurrent validity with increased TIG-EI scores correlated with reduced service user social and global functioning as well as increased scores on measures assessing relatives' distress, expressed emotion and caregiving needs. CONCLUSIONS: Results appear to support these assessments' utility as measures of need for psychosocial intervention and grief among relatives supporting service users experiencing a first episode of psychosis.

GeneCite: a stand-alone open source tool for high-throughput literature and pathway mining.

Systematic extraction of relevant biological facts from available massive scientific knowledge source is emerging as a significant task for the science community. Its success depends on several key factors, including the precision of a given search, the time of its accomplishment, and the communicative prowess of the mined information to the users. GeneCite - a stand-alone Java-based high-throughput data mining tool - is designed to carry out these tasks for several important knowledge sources simultaneously, allowing the users to integrate the results and interpret biological significance in a time-efficient manner. GeneCite provides an integrated high-throughput search platform serving as an information retrieval (IR) tool for probing online literature database (PubMed) and the sequence-tagged sites' database (UniSTS), respectively. It also operates as a data retrieval (DR) tool to mine an archive of biological pathways integrated into the software itself. Furthermore, GeneCite supports a retrieved data management system (DMS) showcasing the final output in a spread-sheet format. Each cell of the output file holds a real-time connection (hyperlink) to the given online archive reachable at the users' convenience. The software is free and currently available online www.bioinformatics.org; www.wrair.army.mil/Resources.

Improving growth of very low birth weight infants in the first 28 days.

OBJECTIVE: To increase weight gain in the first 28 days after birth for very low birth weight (VLBW) infants by isolating and sharing meaningful process differences between high- and low-weight-gain centers within a neonatal network. DESIGN/METHODS: We identified weight gain as an important target for improvement in 1999 for our national group practice of neonatologists. Site-specific average weight gain during the first 28 days was the primary outcome measure. Our target population was defined as inborn infants who survived and remained in the hospital of birth, whose birth weights were between 401 and 1500 g (VLBW), and who were >22 weeks' estimated gestational age. A team of 6 neonatologists and 1 nurse met, reviewed processes that might influence growth, and developed a structured observation guide for site visits. Weight gain data were obtained from an existing administrative database for the period January 1, 1997, through June 30, 1999. Centers were ranked and divided into upper, middle, and lower thirds. Seven team members visited 1 high- and 1 low-weight-gain center without being informed of the center's performance. Following the site visits, the team isolated 16 meaningful differences between high- and low-weight-gain sites. Meaningful differences were defined as processes observed in all or virtually all (for this project, 6 or 7 of 7 centers) of the high and none or virtually none (for this project, 0 or 1 of 7) of the low centers. The meaningful differences were distributed to our medical directors in August 2000 along with their site-specific weight-gain performance. To document the impact of sharing this material, we compared weight gain in a baseline period of January 1 through December 31, 1999 and a posteducational intervention period of January 1 through September 30, 2001. RESULTS: Compared with neonates admitted to our national neonatal practice in 1999, neonates admitted in 2001 were similar in birth weight, gestational age at birth, exposure to antenatal steroids, and male gender. Average daily weight gain during the first 28 days increased from 10.4 +/- 6 g for neonates cared for in 1999 to 12.5 +/- 6 g for neonates cared for in 2001. Thirty-nine of 51 (76%) units noted improvements, 4 were unchanged and 8 noted a decrease in average weight gain. Despite similar average lengths of stay, the average discharge weight for neonates sent home increased from 2.15 +/- 0.5 kg for 1999 to 2.29 +/- 0.5 kg for 2001. There were no differences in frequencies of mortality or major morbidities, including severe intraventricular hemorrhage, retinopathy, or necrotizing enterocolitis, between the 2 time periods. An increase in the use of continuous positive airway pressure was noted in the post implementation period. CONCLUSIONS: Variation in common processes can alter clinical outcomes. Although temporal trends in weight gain may be, in part, responsible for this trend, it appears that isolation and implementation of meaningful differences in processes can augment our desire to rapidly improve clinical outcomes.