Facilitators and barriers to the successful implementation of pediatric antibacterial drug trials: Findings from CTTI's survey of investigators.

An urgent need exists to develop new antibacterial drugs for children. We conducted research with investigators of pediatric antibacterial drug trials to identify facilitators and barriers in the conduct of these trials. Seventy-three investigators completed an online survey assessing the importance of 15 facilitators (grouped in 5 topical categories) and the severity of 36 barriers (grouped in 6 topical categories) to implementing pediatric antibacterial drug trials. Analysis focused on the identification of key factors that facilitate the successful implementation of pediatric antibacterial drug trials and the key barriers to implementation. Almost all investigators identified two factors as very important facilitators: having site personnel for enrollment and having adequate funding. Other top factors were related to staffing. Among the barriers, factors related to parent concerns and consent were prominent, particularly obtaining parental consent when there was disagreement between parents, concerns about the number of blood draws, and concerns about the number of invasive procedures. Having overly narrow eligibility criteria was also identified as a major barrier. The survey findings suggest three areas in which to focus efforts to help facilitate ongoing drug development: (1) improving engagement with parents of children who may be eligible to enroll in a pediatric antibacterial drug trial, (2) broadening inclusion criteria to allow more participants to enroll, and (3) ensuring adequate staffing and establishing sustainable financial strategies, such as funding pediatric trial networks. The pediatric antibacterial drug trials enterprise is likely to benefit from focused efforts by all stakeholders to remove barriers and enhance facilitation

Towards Understanding Photodegradation Pathways in Lignins:The Role of Intramolecular Hydrogen Bonding in Excited States

The photoinduced dynamics of the lignin building blocks syringol, guaiacol, and phenol were studied using time-resolved ion yield spectroscopy and velocity map ion imaging. Following irradiation of syringol and guaiacol with a broad-band femtosecond ultraviolet laser pulse, a coherent superposition of out-of-plane OH torsion and/or OMe torsion/flapping motions is created in the first excited 1ππ* (S1) state, resulting in a vibrational wavepacket, which is probed by virtue of a dramatic nonplanar → planar geometry change upon photoionization from S1 to the ground state of the cation (D0). Any similar quantum beat pattern is absent in phenol. In syringol, the nonplanar geometry in S1 is pronounced enough to reduce the degree of intramolecular H bonding (between OH and OMe groups), enabling H atom elimination from the OH group. For guaiacol, H bonding is preserved after excitation, despite the nonplanar geometry in S1, and prevents O–H bond fission. This behavior affects the propensities for forming undesired phenoxyl radical sites in these three lignin chromophores and provides important insight into their relative “photostabilities” within the larger biopolymer

Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation

Parallel Microbial Ecology of Pasteuria and Nematode Species in Scottish Soils

Copyright © 2020 Orr, Neilson, Freitag, Roberts, Davies, Blok and Cock.Pasteuria spp. are endospore forming bacteria which act as natural antagonists to many of the most economically significant plant parasitic nematodes (PPNs). Highly species-specific nematode suppression may be observed in soils containing a sufficiently high density of Pasteuria spp. spores. This suppression is enacted by the bacteria via inhibition of root invasion and sterilization of the nematode host. Molecular methods for the detection of Pasteuria spp. from environmental DNA (eDNA) have been described; however, these methods are limited in both scale and in depth. We report the use of small subunit rRNA gene metabarcoding to profile Pasteuria spp. and nematode communities in parallel. We have investigated Pasteuria spp. population structure in Scottish soils using eDNA from two sources: soil extracted DNA from the second National Soil Inventory of Scotland (NSIS2); and nematode extracted DNA collected from farms in the East Scotland Farm Network (ESFN). We compared the Pasteuria spp. community culture to both nematode community structure and the physiochemical properties of soils. Our results indicate that Pasteuria spp. populations in Scottish soils are broadly dominated by two sequence variants. The first of these aligns with high identity to Pasteuria hartismeri, a species first described parasitizing Meloidogyne ardenensis, a nematode parasite of woody and perennial plants in northern Europe. The second aligns with a Pasteuria-like sequence which was first recovered from a farm near Edinburgh which was found to contain bacterial feeding nematodes and Pratylenchus spp. encumbered by Pasteuria spp. endospores. Further, soil carbon, moisture, bulk density, and pH showed a strong correlation with the Pasteuria spp. community composition. These results indicate that metabarcoding is appropriate for the sensitive, specific, and semi-quantitative profiling of Pasteuria species from eDNA.Peer reviewe

The association between impulsivity and alcohol/drug use among prison inmates

Background: Few studies have examined the relation between impulsivity and drug involvement with prison inmates, in spite of their heavy drug use. Among this small body of work, most studies look at clinically relevant drug dependence, rather than drug use specifically. Method: N = 242 adult inmates (34.8% female, 52% White) with an average age of 35.58 (SD = 9.19) completed a modified version of the 15-item Barratt Impulsiveness Scale (BIS) and measures assessing lifetime alcohol, opiate, benzodiazepine, cocaine, cannabis, hallucinogen, and polysubstance use. Lifetime users also reported the frequency of use for the 30 days prior to incarceration. Results: Impulsivity was higher among lifetime users (versus never users) of all substances other than cannabis. Thirty day drug use frequency was only related to impulsivity for opiates and alcohol. Discussion: This study extends prior work, by showing that a lifetime history of non-clinical substance use is positively associated with impulsivity among prison inmates. Implications for drug interventions are considered for this population, which is characterized by high rates of substance use and elevated impulsivity

Describing current use, barriers, and facilitators of patient portal messaging for research recruitment: Perspectives from study teams and patients at one institution

Abstract Introduction: The electronic health record (EHR) and patient portal are used increasingly for clinical research, including patient portal recruitment messaging (PPRM). Use of PPRM has grown rapidly; however, best practices are still developing. In this study, we examined the use of PPRM at our institution and conducted qualitative interviews among study teams and patients to understand experiences and preferences for PPRM. Methods: We identified study teams that sent PPRMs and patients that received PPRMs in a 60-day period. We characterized these studies and patients, in addition to the patients’ interactions with the PPRMs (e.g., viewed, responded). From these groups, we recruited study team members and patients for semi-structured interviews. A pragmatic qualitative inquiry framework was used by interviewers. Interviews were audio-recorded and analyzed using a rapid qualitative analysis exploratory approach. Results: Across ten studies, 35,037 PPRMs were sent, 33% were viewed, and 17% were responded to. Interaction rates varied across demographic groups. Six study team members completed interviews and described PPRM as an efficient and helpful recruitment method. Twenty-eight patients completed interviews. They were supportive of receiving PPRMs, particularly when the PPRM was relevant to their health. Patients indicated that providing more information in the PPRM would be helpful, in addition to options to set personalized preferences. Conclusions: PPRM is an efficient recruitment method for study teams and is acceptable to patients. Engagement with PPRMs varies across demographic groups, which should be considered during recruitment planning. Additional research is needed to evaluate and implement recommended changes by study teams and patients

Outcomes of selective nonoperative management of civilian abdominal gunshot wounds: a systematic review and meta-analysis

Abstract Background Although mandatory laparotomy has been standard of care for patients with abdominal gunshot wounds (GSWs) for decades, this approach is associated with non-therapeutic operations, morbidity, and long hospital stays. This systematic review and meta-analysis sought to summarize outcomes of selective nonoperative management (SNOM) of civilian abdominal GSWs. Methods We searched electronic databases (March 1966–April 1, 2017) and reference lists of articles included in the systematic review for studies reporting outcomes of SNOM of civilian abdominal GSWs. We meta-analyzed the associated risks of SNOM-related failure (defined as laparotomy during hospital admission), mortality, and morbidity across included studies using DerSimonian and Laird random-effects models. Between-study heterogeneity was assessed by calculating I2 statistics and conducting tests of homogeneity. Results Of 7155 citations identified, we included 41 studies [n = 22,847 patients with abdominal GSWs, of whom 6777 (29.7%) underwent SNOM]. The pooled risk of failure of SNOM in hemodynamically stable patients without a reduced level of consciousness or signs of peritonitis was 7.0% [95% confidence interval (CI) = 3.9–10.1%; I2 = 92.6%, homogeneity p  0.99). In patients who failed SNOM, the pooled estimate of the risk of therapeutic laparotomy was 68.0% (95% CI = 58.3–77.7%; I2 = 91.5%; homogeneity p < 0.001). Risks of failure of SNOM were lowest in studies that evaluated patients with right thoracoabdomen (3.4%; 95% CI = 0–7.0%; I2 = 0%; homogeneity p = 0.45), flank (7.0%; 95% CI = 3.9–10.1%), and back (3.1%; 95% CI = 0–6.5%) GSWs and highest in those that evaluated patients with anterior abdomen (13.2%; 95% CI = 6.3–20.1%) GSWs. In patients who underwent mandatory abdominopelvic computed tomography (CT), the pooled risk of failure was 4.1% versus 8.3% in those who underwent selective CT (p = 0.08). The overall sample-size-weighted mean hospital length of stay among patients who underwent SNOM was 6 days versus 10 days if they failed SNOM or developed an in-hospital complication. Conclusions SNOM of abdominal GSWs is safe when conducted in hemodynamically stable patients without a reduced level of consciousness or signs of peritonitis. Failure of SNOM may be lower in patients with GSWs to the back, flank, or right thoracoabdomen and be decreased by mandatory use of abdominopelvic CT scans

A search for fast radio bursts associated with gamma-ray bursts

The detection of seven fast radio bursts (FRBs) has recently been reported. FRBs are short duration (~1 ms), highly dispersed radio pulses from astronomical sources. The physical interpretation for the FRBs remains unclear but is thought to involve highly compact objects at cosmological distance. It has been suggested that a fraction of FRBs could be physically associated with gamma-ray bursts (GRBs). Recent radio observations of GRBs have reported the detection of two highly dispersed short duration radio pulses using a 12 m radio telescope at 1.4 GHz. Motivated by this result, we have performed a systematic and sensitive search for FRBs associated with GRBs. We have observed five GRBs at 2.3 GHz using a 26 m radio telescope located at the Mount Pleasant Radio Observatory, Hobart. The radio telescope was automated to rapidly respond to Gamma-ray Coordination Network notifications from the Swift satellite and slew to the GRB position within ~140 s. The data were searched for pulses up to 5000 pc cm−3 in dispersion measure and pulse widths ranging from 640μs to 25.60 ms. We did not detect any events ≥6σ. An in depth statistical analysis of our data shows that events detected above 5σ are consistent with thermal noise fluctuations only. A joint analysis of our data with previous experiments shows that previously claimed detections of FRBs from GRBs are unlikely to be astrophysical. Our results are in line with the lack of consistency noted between the recently presented FRB event rates and GRB event rates

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A life course approach to injury prevention: a "lens and telescope" conceptual model

<p>Abstract</p> <p>Background</p> <p>Although life course epidemiology is increasingly employed to conceptualize the determinants of health, the implications of this approach for strategies to reduce the burden of injuries have received little recognition to date.</p> <p>Methods</p> <p>The authors reviewed core injury concepts and the principles of the life course approach. Based on this understanding, a conceptual model was developed, to provide a holistic view of the mechanisms that underlie the accumulation of injury risk and their consequences over the life course.</p> <p>Results</p> <p>A "lens and telescope" model is proposed that particularly draws on (a) the extended temporal dimension inherent in the life course approach, with links between exposures and outcomes that span many years, or even generations, and (b) an ecological perspective, according to which the contexts in which individuals live are critical, as are changes in those contexts over time.</p> <p>Conclusions</p> <p>By explicitly examining longer-term, intergenerational and ecological perspectives, life course concepts can inform and strengthen traditional approaches to injury prevention and control that have a strong focus on proximal factors. The model proposed also serves as a tool to identify intervention strategies that have co-benefits for other areas of health.</p