The Use of a Pressure-Indicating Sensor Film to Provide Feedback upon Hydrogel-Forming Microneedle Array Self-Application In Vivo

PURPOSE:
To evaluate the combination of a pressure-indicating sensor film with hydrogel-forming microneedle arrays, as a method of feedback to confirm MN insertion in vivo.
METHODS:
Pilot in vitro insertion studies were conducted using a Texture Analyser to insert MN arrays, coupled with a pressure-indicating sensor film, at varying forces into excised neonatal porcine skin. In vivo studies involved twenty human volunteers, who self-applied two hydrogel-forming MN arrays, one with a pressure-indicating sensor film incorporated and one without. Optical coherence tomography was employed to measure the resulting penetration depth and colorimetric analysis to investigate the associated colour change of the pressure-indicating sensor film.
RESULTS:
Microneedle insertion was achieved in vitro at three different forces, demonstrating the colour change of the pressure-indicating sensor film upon application of increasing pressure. When self-applied in vivo, there was no significant difference in the microneedle penetration depth resulting from each type of array, with a mean depth of 237 μm recorded. When the pressure-indicating sensor film was present, a colour change occurred upon each application, providing evidence of insertion.
CONCLUSIONS:
For the first time, this study shows how the incorporation of a simple, low-cost pressure-indicating sensor film can indicate microneedle insertion in vitro and in vivo, providing visual feedback to assure the user of correct application. Such a strategy may enhance usability of a microneedle device and, hence, assist in the future translation of the technology to widespread clinical use.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Reducing child conduct disordered behaviour and improving parent mental health in disadvantaged families: a 12 month follow-up and cost analysis of a parenting intervention

The effectiveness of the Incredible Years Basic parent programme (IYBP) in reducing child conduct problems and improving parent competencies and mental health was examined in a 12-month follow-up. Pre- to post-intervention service use and related costs were also analysed. A total of 103 families and their children (aged 32–88 months), who previously participated in a randomised controlled trial of the IYBP, took part in a 12-month follow-up assessment. Child and parent behaviour and well-being were measured using psychometric and observational measures. An intention-to-treat analysis was carried out using a one-way repeated measures ANOVA. Pairwise comparisons were subsequently conducted to determine whether treatment outcomes were sustained 1 year post-baseline assessment. Results indicate that post-intervention improvements in child conduct problems, parenting behaviour and parental mental health were maintained. Service use and associated costs continued to decline. The results indicate that parent-focused interventions, implemented in the early years, can result in improvements in child and parent behaviour and well-being 12 months later. A reduced reliance on formal services is also indicated.

Exploring the effects of a universal classroom management training programme on teacher and child behaviour: a group randomised controlled trial and cost analysis

Teachers frequently struggle to cope with conduct problems in the classroom. The aim of this study was to assess the effectiveness of the Incredible Years Teacher Classroom Management Training Programme for improving teacher competencies and child adjustment. The study involved a group randomised controlled trial which included 22 teachers and 217 children (102 boys and 115 girls). The average age of children included in the study was 5.3 years (standard deviation = 0.89). Teachers were randomly allocated to an intervention group (n = 11 teachers; 110 children) or a waiting-list control group (n = 11; 107 children). The sample also included 63 ‘high-risk’ children (33 intervention; 30 control), who scored above the cut-off (>12) on the Strengths and Difficulties Questionnaire for abnormal socioemotional and behavioural difficulties. Teacher and child behaviours were assessed at baseline and 6 months later using psychometric and observational measures. Programme delivery costs were also analysed. Results showed positive changes in teachers’ self-reported use of positive classroom management strategies (effect size = 0.56), as well as negative classroom management strategies (effect size = −0.43). Teacher reports also highlight improvements in the classroom behaviour of the high-risk group of children, while the estimated cost of delivering the Incredible Years Teacher Classroom Management Training Programme was modest. However, analyses of teacher and child observations were largely non-significant. A need for further research exploring the effectiveness and cost-effectiveness of the Incredible Years Teacher Classroom Management Training Programme is indicated.

Time-Independent Discrete Gaussian Sampling for Post-Quantum Cryptography

As the development of a viable quantum computer nears, existing widely used public-key cryptosystems, such as RSA, will no longer be secure. Thus, significant effort is being invested into post-quantum cryptography (PQC). Lattice-based cryptography (LBC) is one such promising area of PQC, which offers versatile, efficient, and high performance security services. However, the vulnerabilities of these implementations against side-channel attacks (SCA) remain significantly understudied. Most, if not all, lattice-based cryptosystems require noise samples generated from a discrete Gaussian distribution, and a successful timing analysis attack can render the whole cryptosystem broken, making the discrete Gaussian sampler the most vulnerable module to SCA. This research proposes countermeasures against timing information leakage with FPGA-based designs of the CDT-based discrete Gaussian samplers with constant response time, targeting encryption and signature scheme parameters. The proposed designs are compared against the state-of-the-art and are shown to significantly outperform existing implementations. For encryption, the proposed sampler is 9x faster in comparison to the only other existing time-independent CDT sampler design. For signatures, the first time-independent CDT sampler in hardware is proposed. 

Behavior change theory, content and delivery of interventions to enhance adherence in chronic respiratory disease: A systematic review

Background: We sought to describe the theory used to design treatment adherence interventions, the content delivered, and the mode of delivery of these interventions in chronic respiratory disease. Methods: We included randomized controlled trials of adherence interventions (compared to another intervention or control) in adults with chronic respiratory disease (8 databases searched; inception until March 2015). Two reviewers screened and extracted data: post-intervention adherence (measured objectively); behavior change theory, content (grouped into psychological, education and self-management/supportive, telemonitoring, shared decision-making); and delivery. “Effective” studies were those with p < 0.05 for adherence rate between groups. We conducted a narrative synthesis and assessed risk of bias. Results: 12,488 articles screened; 46 included studies (n = 42,91% in OSA or asthma) testing 58 interventions (n = 27, 47% were effective). Nineteen (33%) interventions (15 studies) used 12 different behavior change theories. Use of theory (n = 11,41%) was more common amongst effective interventions. Interventions were mainly educational, self-management or supportive interventions (n = 27,47%). They were commonly delivered by a doctor (n = 20,23%), in face-to-face (n = 48,70%), one-to-one (n = 45,78%) outpatient settings (n = 46,79%) across 2–5 sessions (n = 26,45%) for 1–3 months (n = 26,45%). Doctors delivered a lower proportion (n = 7,18% vs n = 13,28%) and pharmacists (n = 6,15% vs n = 1,2%) a higher proportion of effective than ineffective interventions. Risk of bias was high in >1 domain (n = 43, 93%) in most studies. Conclusions: Behavior change theory was more commonly used to design effective interventions. Few adherence interventions have been developed using theory, representing a gap between intervention design recommendations and research practice.

Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R(2 ) = 0.0021; P = 0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies.

Endothelial cell-derived Pentraxin 3 limits the vasoreparative therapeutic potential of Circulating Angiogenic Cells

AIMS: Circulating Angiogenic Cells (CACs) promote revascularization of ischemic tissues although their underlying mechanism of action and the consequences of delivering varying numbers of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation.

METHODS & RESULTS: CACs at low (2x10(5)cells/ml) and mid (2x10(6)cells/ml) cellular densities significantly enhanced endothelial cell (EC) tube formation in vitro, while high density CACs (2x10(7)cells/ml) significantly inhibited this angiogenic process. In vivo, Matrigel-based angiogenesis assays confirmed mid-density CACs as pro-angiogenic and high density CACs as anti-angiogenic. Secretome characterization of CAC-EC conditioned media identified pentraxin 3 (PTX3) as only present in the high density CAC-EC co-culture. Recombinant PTX3 inhibited endothelial tube formation in vitro and in vivo Importantly, our data revealed that the anti-angiogenic effect observed in high density CAC-EC co-cultures was significantly abrogated when PTX3 bioactivity was blocked using neutralizing antibodies or PTX3 siRNA in endothelial cells. We show evidence for an endothelial source of PTX3, triggered by exposure to high density CACs. In addition, we confirmed that PTX3 inhibits FGF2-mediated angiogenesis, and that the PTX3 N-terminus, containing the FGF-binding site, is responsible for such anti-angiogenic effects.

CONCLUSIONS: Endothelium, when exposed to high density CACs, releases PTX3 which markedly impairs the vascular regenerative response in an autocrine manner. Therefore, CAC density and accompanying release of angiocrine PTX3 are critical considerations when using these cells as a cell therapy for ischemic disease.

The Adolescent Empathy Paradox and Juvenile Offending

Thesis (Master's)--University of Washington, 2016-08

Trafficking in human beings for for forced labour in domestic and international law: a comparative legal study of the kingdom of Saudi Arabia and the United Kingdom

This thesis examines the effect of combating of human trafficking as a crime. Special emphasis has been placed on forced labour and the rights of trafficked victims and their protection. The study explores various legislations undertaken at regional, national and international levels and considers rights of trafficked victims under international human rights and Islamic rights. The aim of the thesis is to provide a critical and comparative analysis of the legal systems of the Kingdom of Saudi Arabia (KSA) and the United Kingdom (UK) in terms of human trafficking. The thesis consists of eight chapter; each covering a different aspect of the study. It begins by providing background information regarding the issue of human trafficking and proceeds to examine developments of legal frameworks across the two jurisdictions to combat this crime and penalize the criminals. It seeks to examine the legal system pertaining to human trafficking for forced labour and analyse the three distinct platforms, that is, prevention, protection, and punishment, by comparing the legal systems of the KSA and the UK. The examination of both countries aims to identify the strength and weaknesses of the KSA system as compared to the UK system. Thus, it concludes that the KSA can improve its ranking from Tier 2 watch list to Tier 1 if reforms are introduced in the legislation and enforcement domains. The study also demonstrates how the UK and the KSA portray ‘human trafficking’ in their regional laws. A problem often faced during the information-gathering and investigation stages is the lack of available evidence against traffickers, a particular issue in the KSA. The thesis concludes that the transnational aspect of this phenomenon makes it necessary to establish a thorough and comprehensive legal framework to cover all matters pertaining to this crime, including the protection of victims and punishment of criminals in the KSA and the UK, including immigration and ‘kafala’ strategies that may be of value in future researches.

Constructivism, constitutionalism and the EU's area of freedom security and justice post-Lisbon

This essay addresses the fundamental conceptual challenges which face the development of the Area of Freedom Security and Justice (AFSJ) in the post-Lisbon Treaty era. It argues that Onuf style constructivism is a valid lens with which to examine the development of the AFSJ to date, involving as it does the development of a shared understanding by practitioners, predominantly law enforcement and prosecution professionals, within the structures provided for them, in order to develop a completely new area of law and practice. While this approach will continue to need to be deployed in the development of further new operational areas, such as cybercrime, a new approach is now required, that of constitutionalism. A variety of forms of constitutionalism are then examined in order to establish their suitability as a mode of analysis for these developments.

New challenges for the EU internal security strategy

In recent years, the EU and its member states have experienced a number of changes, as well as challenges, in the areas of politics, economics, security and law. As these areas are interconnected, changes and challenges to any of them have implications for the others, as well as implications for the populations and institutions of the EU or those coming into contact with its international power and influence. This edited collection focuses primarily on security and law, particularly the EU’s internal security strategy. The EU’s Internal Security Strategy, adopted by the Spanish presidency early in 2010, followed the Lisbon Treaty in 2009, building on previous developments within the EU in the Area of Freedom Security and Justice (AFSJ) policy. The focus of the EU Internal Security Strategy is to prevent and combat “serious and organised crime, terrorism and cybercrime, in strengthening the management of our external borders and in building resilience to natural and man-made disasters”. The Internal Security strategy intersects and overlaps with the European Union’s Counter-terrorism strategy, the Strategy for the External Dimension of JHA, and the EU’s Security Strategy. The role of and interaction between these strategies, their supplementing documents, and their implications for crime, victims, the law, political relations, democracy and human rights, form the backdrop against which the chapters in this collection are written. Building on original research by its contributors, this collection comprises work by authors from a wide variety of academic and professional areas and perspectives, as well as different countries, on a variety of areas and issues related to or raised by the EU’s Internal Security Strategy, from intelligence-led policing to human trafficking and port security. This book examines, from a wide variety of disciplinary perspectives including law, geography, politics and practice, both this further refinement of existing internal provisions on cross-border crime, and the increasing external relations of the EU in the AFSJ.