Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators

Complexity metrics and user strength perceptions of the pattern-lock graphical authentication method

One of the most popular contemporary graphical password approaches is the Pattern-Lock authentication mechanism that comes integrated with the Android mobile operating system. In this paper we investigate the impact of password strength meters on the selection of a perceivably secure pattern. We first define a suitable metric to measure pattern strength, taking into account the constraints imposed by the Pattern-Lock mechanism's design. We then implement an app via which we conduct a survey for Android users, retaining demographic information of responders and their perceptions on what constitutes a pattern complex enough to be secure. Subsequently, we display a pattern strength meter to the participant and investigate whether this additional prompt influences the user to change their pattern to a more effective and complex one. We also investigate potential correlations between our findings and results of a previous pilot study in order to detect any significant biases on setting a Pattern-Lock. © 2014 Springer International Publishing

Complexity metrics and user strength perceptions of the pattern-lock graphical authentication method

One of the most popular contemporary graphical password approaches is the Pattern-Lock authentication mechanism that comes integrated with the Android mobile operating system. In this paper we investigate the impact of password strength meters on the selection of a perceivably secure pattern. We first define a suitable metric to measure pattern strength, taking into account the constraints imposed by the Pattern-Lock mechanism's design. We then implement an app via which we conduct a survey for Android users, retaining demographic information of responders and their perceptions on what constitutes a pattern complex enough to be secure. Subsequently, we display a pattern strength meter to the participant and investigate whether this additional prompt influences the user to change their pattern to a more effective and complex one. We also investigate potential correlations between our findings and results of a previous pilot study in order to detect any significant biases on setting a Pattern-Lock. © 2014 Springer International Publishing

Making Health Markets Work Better for Poor People: the Case of Informal Providers

There has been a dramatic spread of market relationships in many low- and middle-income countries. This spread has been much faster than the development of the institutional arrangements to influence the performance of health service providers. In many countries poor people obtain a large proportion of their outpatient medical care and drugs from informal providers working outside a regulatory framework, with deleterious consequences in terms of the safety and efficacy of treatment and its cost. Interventions that focus only on improving the knowledge of these providers have had limited impact. There is a considerable amount of experience in other sectors with interventions for improving the performance of markets that poor people use. This paper applies lessons from this experience to the issue of informal providers, drawing on the findings of studies in Bangladesh and Nigeria. These studies analyse the markets for informal health care services in terms of the sources of health-related knowledge for the providers, the livelihood strategies of these providers and the institutional arrangements within which they build and maintain their reputation. The paper concludes that there is a need to build a systematic understanding of these markets to support collaboration between key actors in building institutional arrangements that provide incentives for better performance.ESR

Efficient preparation and detection of microwave dressed-state qubits and qutrits with trapped ions

We demonstrate a method for preparing and detecting all eigenstates of a three-level microwave dressed system with a single trapped ion. The method significantly reduces the experimental complexity of gate operations with dressed-state qubits, as well as allowing all three of the dressed states to be prepared and detected, thereby providing access to a qutrit that is well protected from magnetic field noise. In addition, we demonstrate individual addressing of the clock transitions in two ions using a strong static magnetic field gradient, showing that our method can be used to prepare and detect microwave dressed states in a string of ions when performing multi-ion quantum operations with microwave and radio frequency fields. The individual addressability of clock transitions could also allow for the control of pairwise interaction strengths between arbitrary ions in a string using lasers

The narratives of Hardship: : The new and the old poor in the aftermath of the 2008 crisis in Europe

This document is the Accepted Manuscript version of the following article: Hulya Dagdeviren, Matthew Donoghue, and Lars Meier, ‘The narratives of hardship: the new and the old poor in the aftermath of the 2008 crisis in Europe’, The Sociological Review, vol. 65 (2): 369-385, May 2017. The final, definitive version of record is available online at doi: https://doi.org/10.1111/1467-954X.12403. Published by SAGE.This paper examines poverty and hardship in Europe after the 2008 crisis, using household interviews in nine European countries. A number of findings deserve highlighting. First, making a distinction between ‘the old poor’ (those who lived in poverty before as well as after the crisis) and ‘the new poor’ (thosewho fell into hardship after the crisis), we show that hardship is experienced quite differently by these groups. Second, the household narratives showed that while material deprivations constitute an important aspect of hardship, the themes of insecurity and dependency also emerged as fundamental dimensions. In contrast to popular political discourse in countries such as the UK, dependency on welfare or family was experienced as a source of distress and manifested as a form of hardship by participants in all countries covered in this study.Peer reviewedFinal Accepted Versio

Constraining the formation history of the TOI-1338/BEBOP-1 circumbinary planetary system

The recent discovery of multiple planets in the circumbinary system TOI-1338/BEBOP-1 raises questions about how such a system formed. The formation of the system was briefly explored in the discovery paper, but only to answer the question do current pebble accretion models have the potential to explain the origin of the system? We use a global model of circumbinary planet formation that utilises N-body simulations, including prescriptions for planet migration, gas and pebble accretion, and interactions with a circumbinary disc, to explore the disc parameters that could have led to the formation of the TOI-1338/BEBOP-1 system. With the disc lifetime being the main factor in determining how planets form, we limit our parameter space to those that determine the disc lifetime. These are: the strength of turbulence in the disc, the initial disc mass, and the strength of the external radiation field that launches photoevaporative winds. When comparing the simulated systems to TOI-1338/BEBOP-1, we find that only discs with low levels of turbulence are able to produce similar systems. The radiation environment has a large effect on the types of planetary systems that form, whilst the initial disc mass only has limited impact since the majority of planetary growth occurs early in the disc lifetime. With the most TOI-1338/BEBOP-1 like systems all occupying similar regions of parameter space, our study shows that observed circumbinary planetary systems can potentially constrain the properties of planet forming discs.Comment: Accepted for publication in MNRAS, 15 pages, 10 figure

Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous, intramuscular, sub-cutaneous and oral administration in healthy volunteers

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. Treatment success is dependent on early intervention and rapid systemic exposure to TXA. The requirement for intravenous (IV) administration can in some situations limit accessibility to TXA therapy. Here we employ physiologically based pharmacokinetic modelling (PBPK) to evaluate if adequate TXA exposure maybe achieved when given via different routes of administration. METHODS: A commercially available PBPK software (GastroPlus®) was used to model published TXA pharmacokinetics. IV, oral and intramuscular (IM) models were developed using healthy volunteer PK data from twelve different single dose regimens (n=48 participants). The model was verified using separate IV and oral validation datasets (n=26 participants). Oral, IM and sub-cutaneous (SQ) dose finding simulations were performed. RESULTS: Across the different TXA regimens evaluated TXA plasma concentrations varied from 0.1 to 94.0 µg/mL. Estimates of the total plasma clearance of TXA ranged from 0.091 to 0.104 L/h/kg, oral bioavailability from 36 to 67 % and Tmax from 2.6 to 3.2 and 0.4 to 1.0 hours following oral and intramuscular administration respectively. Variability in the observed TXA PK could be captured through predictable demographic effects on clearance, combined with intestinal permeability and stomach transit time following oral administration and muscle blood flow and muscle/plasma partition coefficients following intra-muscular dosing. CONCLUSIONS: This study indicates that intramuscular administration is the non-intravenous route of administration with the most potential for achieving targeted TXA exposures. Plasma levels following an IM dose of 1000 mg TXA are predicted to exceed 15 mg/mL in < 15 minutes and be maintained above this level for approximately 3 hours, achieving systemic exposure (AUC0-6) of 99 to 105 µg*hr/mL after a single dose. Well-designed clinical trials to verify these predictions and confirm the utility of intramuscular TXA are recommended

Digital health and inequalities in access to health services in Bangladesh: Mixed methods study

Background: Globally, the rapid growth of technology and its use as a development solution has generated much interest in digital health. In line with global trends, Bangladesh is also integrating technology into its health system to address disparities. Strong political endorsement and uptake of digital platforms by the government has influenced the rapid proliferation of such initiatives in the country. This paper aims to examine the implications of digital health on access to health care in Bangladesh, considering who uses electronic devices to access health information and services and why. Objective: This study aims to understand how access to health care and related information through electronic means (digital health) is affected by sociodemographic determinants (ie, age, gender, education, socioeconomic status, and personal and household ownership of mobile phones) in a semiurban community in Bangladesh. Methods: A cross-sectional survey of 854 households (between October 2013 and February 2014) and 20 focus group discussions (between February 2017 and March 2017) were conducted to understand (1) who owns electronic devices; (2) who, among the owners, uses these to access health information and services and why; (3) the awareness of electronic sources of health information; and (4) the role of intermediaries (family members or peers who helped to look for health information using electronic devices). Results: A total of 90.3% (771/854) of households (471/854, 55.2% of respondents) owned electronic devices, mostly mobile phones. Among these, 7.2% (34/471) used them to access health information or services. Middle-aged (35-54 years), female, less (or not) educated, and poorer people used these devices the least (α=.05, α is the level of significance). The lack of awareness, discomfort, differences with regular care-seeking habits, lack of understanding and skills, and proximity to a health facility were the main reasons for not using devices to access digital health. Conclusions: Although influenced by sociodemographic traits, access to digital health is not merely related to device ownership and technical skill. Rather, it is a combination of general health literacy, phone ownership, material resources, and technical skill as well as social recognition of health needs and inequity. This study’s findings should serve as a basis for better integrating technology within the health system and ensuring equitable access to health care