Chlorination and oxidation of heparin and hyaluronan by hypochlorous acid and hypochlorite anions: effect of sulfate groups on reaction pathways and kinetics.

Hypochlorous acid (HOCl), produced in inflammatory conditions by the enzyme myeloperoxidase, and its anion hypochlorite (OCl(-)) exist in vivo at almost equal concentrations. Their reactions with hyaluronan and heparin (as a model for sulfated glycosaminoglycans in the extracellular matrix) have been studied as a function of pH. The major product in these reactions is the chloramide derivative of the glycosaminoglycans. Spectral, chloramide yield, and kinetic measurements show sharply contrasting behavior of heparin and hyaluronan and the data allow the calculation of second-order rate constants for the reactions of both HOCl and OCl(-) for all reaction pathways leading to the formation of chloramides and also oxidation products. By comparison with hyaluronan, it can be demonstrated that both N-sulfate and O-sulfate groups in heparin influence the proportions of these pathways in this glycosaminoglycan. Evidence is also given for further oxidation pathways involving a reaction of HOCl with the chloramide product of hyaluronan but not with heparin. The significance of these results for the mechanisms of inflammation, particularly for fragmentation of extracellular matrix glycosaminoglycans, is discussed

Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Beating the channel capacity limit for linear photonic superdense coding

Dense coding is arguably the protocol that launched the field of quantum communication. Today, however, more than a decade after its initial experimental realization, the channel capacity remains fundamentally limited as conceived for photons using linear elements. Bob can only send to Alice three of four potential messages owing to the impossibility of carrying out the deterministic discrimination of all four Bell states with linear optics, reducing the attainable channel capacity from 2 to log_2 3 \approx 1.585 bits. However, entanglement in an extra degree of freedom enables the complete and deterministic discrimination of all Bell states. Using pairs of photons simultaneously entangled in spin and orbital angular momentum, we demonstrate the quantum advantage of the ancillary entanglement. In particular, we describe a dense-coding experiment with the largest reported channel capacity and, to our knowledge, the first to break the conventional linear-optics threshold. Our encoding is suited for quantum communication without alignment and satellite communication.Comment: Letter: 6 pages, 4 figures. Supplementary Information: 4 pages, 1 figur

Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

The Scottish clinical supervision model for midwives

Following a change in UK legislation, the Nursing and Midwifery Council (NMC) model of statutory supervision for midwives ceased in 2017. In response, the Scottish Government (SG) and NHS Education for Scotland (NES) worked with the NHS Health Boards to develop a new employer-led model of clinical supervision. The aim of this new model is to help midwives provide improved services, safer care and improved outcomes for childbearing women and infants in keeping with professional regulation. The new Scottish Clinical Supervision Model is also designed to increase midwives personal wellbeing and help them deal with everyday challenges of clinical practice. This design of supervision is a radical departure from the prior NMC model, given that it incorporates facilitation and coaching methods which teach midwives to respond, reflect, and restore self, and through doing so reduce stress and increase resilience. In an attempt to improve nurturing leadership, the key components of this new model are underpinned by a person-centred approach, during which the supervisor provides unconditional positive regard and empathy towards the supervisee. Equipping midwives to develop contemporary supervision is supported by NES through online education that can be accessed at: https://www.nes.scot.nhs.uk/education-and-training/by-theme-initiative/maternity-care/about-us/clinical-supervision.asp

Psychosocial issues of women with type 1 diabetes transitioning to motherhood: a structured literature review

BACKGROUND: Life transitions often involve complex decisions, challenges and changes that affect diabetes management. Transition to motherhood is a major life event accompanied by increased risk that the pregnancy will lead to or accelerate existing diabetes-related complications, as well as risk of adverse pregnancy outcomes, all of which inevitably increase anxiety. The frequency of hyperglycaemia and hypoglycaemia often increases during pregnancy, which causes concern for the health and physical well-being of the mother and unborn child. This review aimed to examine the experiences of women with T1DM focusing on the pregnancy and postnatal phases of their transition to motherhood. METHODS: The structured literature review comprised a comprehensive search strategy identifying primary studies published in English between 1990-2012. Standard literature databases were searched along with the contents of diabetes-specific journals. Reference lists of included studies were checked. Search terms included: 'diabetes', 'type 1', 'pregnancy', 'motherhood', 'transition', 'social support', 'quality of life' and 'psychological well-being'. RESULT: Of 112 abstracts returned, 62 articles were reviewed in full-text, and 16 met the inclusion criteria. There was a high level of diversity among these studies but three common key themes were identified. They related to physical (maternal and fetal) well-being, psychological well-being and social environment. The results were synthesized narratively. CONCLUSION: Women with type 1 diabetes experience a variety of psychosocial issues in their transition to motherhood: increased levels of anxiety, diabetes-related distress, guilt, a sense of disconnectedness from health professionals, and a focus on medicalisation of pregnancy rather than the positive transition to motherhood. A trusting relationship with health professionals, sharing experiences with other women with diabetes, active social support, shared decision and responsibilities for diabetes management assisted the women to make a positive transition. Health professionals can promote a positive transition to motherhood by proactively supporting women with T1DM in informed decision-making, by facilitating communication within the healthcare team and co-ordinating care for women with type 1 diabetes transitioning to motherhood

Effectiveness of motivational interviewing and physical activity on prescription on leisure exercise time in subjects suffering from mild to moderate hypertension

<p>Abstract</p> <p>Background</p> <p>Physical inactivity is considered to be the strongest individual risk factor for poor health in Sweden. It has been shown that increased physical activity can reduce hypertension and the risk of developing cardiovascular diseases. The objective of the present pilot study was to investigate whether a combination of Motivational Interviewing (MI) and Physical Activity on Prescription (PAP) would increase leisure exercise time and subsequently improve health-related variables.</p> <p>Methods</p> <p>This pilot study was of a repeated measures design, with a 15 months intervention in 31 patients with mild to moderate hypertension. Primary outcome parameter was leisure exercise time and secondary outcome parameters were changes in blood pressure, Body Mass Index (BMI), waist circumference, lipid status, glycosylated haemoglobin (HbA1c) and maximal oxygen uptake (VO_{2 max}). Assessments of the outcome parameters were made at baseline and after 3, 9 and 15 months.</p> <p>Results</p> <p>Leisure exercise time improved significantly from < 60 min/week at baseline to a mean activity level of 300 (± 165) minutes/week at 15 months follow up. Furthermore, statistically significant improvements (p < 0.05) were observed in systolic (-14,5 ± 8.3 mmHg) and diastolic blood pressure (-5,1 ± 5.8 mmHg), heart rate (-4.9 ± 8.7 beats/min, weight (-1.2 ± 3.4 kg) BMI -0.6 ± 1.2 kg/m²), waist circumference (-3.5 ± 4.1 cm) as well as in VO_{2 max}(2.94 ± 3.8 ml/kg and 0.23, ± 0.34 lit/min) upon intervention as compared to baseline.</p> <p>Conclusions</p> <p>A 15 month intervention period with MI, in combination with PAP, significantly increased leisure exercise time and improved health-related variables in hypertensive patients. This outcome warrants further research to investigate the efficacy of MI and PAP in the treatment of mild to moderate hypertension.</p

Age shall not weary us: Deleterious effects of self-regulation depletion are specific to younger adults

Self-regulation depletion (SRD), or ego-depletion, refers to decrements in self-regulation performance immediately following a different self-regulation-demanding activity. There are now over a hundred studies reporting SRD across a broad range of tasks and conditions. However, most studies have used young student samples. Because prefrontal brain regions thought to subserve self-regulation do not fully mature until 25 years of age, it is possible that SRD effects are confined to younger populations and are attenuated or disappear in older samples. We investigated this using the Stroop color task as an SRD induction and an autobiographical memory task as the outcome measure. We found that younger participants (<25 years) were susceptible to depletion effects, but found no support for such effects in an older group (40–65 years). This suggests that the widely-reported phenomenon of SRD has important developmental boundary conditions casting doubt on claims that it represents a general feature of human cognition

Is there a cloud in the silver lining for imatinib?

Imatinib mesylate (Gleevec&#174; or Glivec&#174;), a small molecule tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia, has been said to herald the dawn of a new er-a of rationally designed, molecularly targeted oncotherapy. Lurking on the same new horizon, however, is the age-old spectre of drug resistance. This review sets the intoxicating clinical perspective against the more sobering laboratory evidence of such divergent mechanisms of imatinib resistance as gene amplification and stem cell quiescence. Polychemotherapy has already been considered to combat resistance, but a more innovative, as yet unformulated, approach may be advocated