History of Northfield, New Hampshire, 1780-1905. In two parts with many biographical sketches and portraits; also pictures of public buildings and private residences.

Pt. 2 : Genealogies

Wnt16 Elicits a Protective Effect Against Fractures and Supports Bone Repair in Zebrafish

Bone homeostasis is a dynamic, multicellular process which is required throughout life to maintain bone integrity, prevent fracture and respond to skeletal damage. WNT16 has been linked to bone fragility and osteoporosis in human genome wide association studies, as well as the functional haematopoiesis of leukocytes in vivo. However, the mechanisms by which WNT16 promotes bone health and repair are not fully understood. We used CRISPR-Cas9 to generate mutant zebrafish lacking Wnt16 (wnt16-/-) to study its effect on bone dynamically. wnt16 mutants displayed variable tissue mineral density and were susceptible to spontaneous fractures and the accumulation of bone calluses at an early age. Fractures were induced in the lepidotrichia of the caudal fins of wnt16-/- and wild type (WT) zebrafish; this model was used to probe the mechanisms by which Wnt16 regulates skeletal and immune cell-dynamics in vivo. In WT fins, wnt16 expression increased significantly during the early stages for bone repair. Mineralization of bone during fracture repair was significantly delayed in wnt16 mutants compared to WT zebrafish. Surprisingly, we found no evidence that the recruitment of innate immune cells to fractures or soft callus formation was altered in wnt16 mutants. However, osteoblast recruitment was significantly delayed in wnt16 mutants post-fracture, coinciding with precocious activation of the canonical Wnt signalling pathway. In situ hybridization suggests that canonical Wnt-responsive cells within fractures are osteoblast progenitors, and that osteoblast differentiation during bone repair is coordinated by the dynamic expression of runx2a and wnt16. This study highlights zebrafish as an emerging model for functionally validating osteoporosis-associated genes and investigating fracture repair dynamically in vivo. Using this model, we demonstrate that Wnt16 protects against fracture and supports bone repair, likely by modulating canonical Wnt activity, via runx2a, to facilitate osteoblast differentiation and bone matrix deposition

Interventions for treating urinary incontinence after stroke in adults

Background Urinary incontinence can affect 40% to 60% of people admitted to hospital after a stroke, with 25% still having problems when discharged from hospital and 15% remaining incontinent after one year. This is an update of a review published in 2005 and updated in 2008. Objectives To assess the effects of interventions for treating urinary incontinence after stroke in adults at least one‐month post‐stroke. Search methods We searched the Cochrane Incontinence and Cochrane Stroke Specialised Registers (searched 30 October 2017 and 1 November 2017 respectively), which contain trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearched journals and conference proceedings. Selection criteria We included randomised or quasi‐randomised controlled trials. Data collection and analysis Two review authors independently undertook data extraction, risk of bias assessment and implemented GRADE. Main results We included 20 trials (reporting 21 comparisons) with 1338 participants. Data for prespecified outcomes were not available except where reported below. Intervention versus no intervention/usual care Behavioural interventions: Low‐quality evidence suggests behavioural interventions may reduce the mean number of incontinent episodes in 24 hours (mean difference (MD) –1.00, 95% confidence interval (CI) –2.74 to 0.74; 1 trial; 18 participants; P = 0.26). Further, low‐quality evidence from two trials suggests that behavioural interventions may make little or no difference to quality of life (SMD ‐0.99, 95% CI ‐2.83 to 0.86; 55 participants). Specialised professional input interventions: One trial of moderate‐quality suggested structured assessment and management by continence nurse practitioners probably made little or no difference to the number of people continent three months after treatment (risk ratio (RR) 1.28, 95% CI 0.81 to 2.02; 121 participants; equivalent to an increase from 354 to 453 per 1000, 95% CI 287 to 715). Complementary therapy: Five trials assessed complementary therapy using traditional acupuncture, electroacupuncture and ginger‐salt‐partitioned moxibustion plus routine acupuncture. Low‐quality evidence from five trials suggested that complementary therapy may increase the number of participants continent after treatment; participants in the treatment group were three times more likely to be continent (RR 2.82, 95% CI 1.57 to 5.07; 524 participants; equivalent to an increase from 193 to 544 per 1000, 95% CI 303 to 978). Adverse events were reported narratively in one study of electroacupuncture, reporting on bruising and postacupuncture abdominal pain in the intervention group. Physical therapy: Two trials reporting three comparisons suggest that physical therapy using transcutaneous electrical nerve stimulation (TENS) may reduce the mean number of incontinent episodes in 24 hours (MD –4.76, 95% CI –8.10 to –1.41; 142 participants; low‐quality evidence). One trial of TENS reporting two comparisons found that the intervention probably improves overall functional ability (MD 8.97, 95% CI 1.27 to 16.68; 81 participants; moderate‐quality evidence). Intervention versus placebo Physical therapy: One trial of physical therapy suggests TPTNS may make little or no difference to the number of participants continent after treatment (RR 0.75, 95% CI 0.19 to 3.04; 54 participants) or number of incontinent episodes (MD –1.10, 95% CI –3.99 to 1.79; 39 participants). One trial suggested improvement in the TPTNS group at 26‐weeks (OR 0.04, 95% CI 0.004 to 0.41) but there was no evidence of a difference in perceived bladder condition at six weeks (OR 2.33, 95% CI 0.63 to 8.65) or 12 weeks (OR 1.22, 95% CI 0.29 to 5.17). Data from one trial provided no evidence that TPTNS made a difference to quality of life measured with the ICIQLUTSqol (MD 3.90, 95% CI –4.25 to 12.05; 30 participants). Minor adverse events, such as minor skin irritation and ankle cramping, were reported in one study. Pharmacotherapy interventions: There was no evidence from one study that oestrogen therapy made a difference to the mean number of incontinent episodes per week in mild incontinence (paired samples, MD –1.71, 95% CI –3.51 to 0.09) or severe incontinence (paired samples, MD –6.40, 95% CI –9.47 to –3.33). One study reported no adverse events. Specific intervention versus another intervention Behavioural interventions: One trial comparing a behavioural intervention (timed voiding) with a pharmacotherapy intervention (oxybutynin) contained no useable data. Complementary therapy: One trial comparing different acupuncture needles and depth of needle insertion to assess the effect on incontinence reported that, after four courses of treatment, 78.1% participants in the elongated needle group had no incontinent episodes versus 40% in the filiform needle group (57 participants). This trial was assessed as unclear or high for all types of bias apart from incomplete outcome data. Combined intervention versus single intervention One trial compared a combined intervention (sensory motor biofeedback plus timed prompted voiding) against a single intervention (timed voiding). The combined intervention may make little or no difference to the number of participants continent after treatment (RR 0.55, 95% CI 0.06 to 5.21; 23 participants; equivalent to a decrease from 167 to 92 per 1000, 95% CI 10 to 868) or to the number of incontinent episodes (MD 2.20, 95% CI 0.12 to 4.28; 23 participants). Specific intervention versus attention control Physical therapy interventions: One study found TPTNS may make little or no difference to the number of participants continent after treatment compared to an attention control group undertaking stretching exercises (RR 1.33, 95% CI 0.38 to 4.72; 24 participants; equivalent to an increase from 250 to 333 per 1000, 95% CI 95 to 1000). Authors' conclusions There is insufficient evidence to guide continence care of adults in the rehabilitative phase after stroke. As few trials tested the same intervention, conclusions are drawn from few, usually small, trials. CIs were wide, making it difficult to ascertain if there were clinically important differences. Only four trials had adequate allocation concealment and many were limited by poor reporting, making it impossible to judge the extent to which they were prone to bias. More appropriately powered, multicentre trials of interventions are required to provide robust evidence for interventions to improve urinary incontinence after stroke

Inequalities in access to health and social care among adults with multiple sclerosis: A scoping review of the literature

Variations in access to health care are known to contribute to differences in life expectancy, morbidity and health-related quality-of-life across population subgroups. We undertook a scoping review to identify what is known about in-country variations in access to services for adults with multiple sclerosis and to identify gaps in the literature to inform future research and national policies. We searched MEDLINE, CINAHL, EMBASE, PSYCHINFO, SocINDEX and Social Science Abstracts from inception to end of December 2016 for quantitative studies which had investigated differences in access to prevention services, healthcare services, treatments and social care between inequality groups, defined using the PROGRESS-PLUS framework. A total of 4959 unique abstracts yielded 36 papers which met our eligibility criteria. Only 3 studies were cohort studies and only 4 were population-based; most were from the United States (n = 27). There were 6 studies on access to MS focused care and 6 on access to Disease Modifying drugs. There were 3 studies on access to prevention/lifestyle programmes and none on access to welfare services or information support. There were no papers examining inequalities in access for 'vulnerable' groups, such as, those with learning disability. In the available studies, there was evidence of inequalities in access to services with a trend for worse access among men, older age groups, those from lower socio-economic groups or the least educated, non-caucasians, those with mental health problems and those from rural areas. In the studies on access to disease modifying treatments, older age and lower socioeconomic status were consistently associated with a lower rate of uptake, while race and gender were not. Inequalities or disparities in access to all levels of services and treatments will need to be addressed through a strategic research agenda with an emphasis on population-based studies and development and evaluation of interventions to reduce inequality. [Abstract copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Developing clinical academic researchers: insights from practitioners and managers in nursing, midwifery and allied health

Background: Developing a clinical academic role in Nursing, Midwifery and the Allied Health Professions (NMAHP) is challenging due to lack of a national career pathway, recognition and understanding of the role. Aims: This evaluation explored perspectives of aspiring or active clinical academics and health care managers in NMAHP about the benefits, barriers and enablers of engagement in these career pathways. Methods: Eight workshops were facilitated across England (four each for managers and prospective clinical academics); 162 participants shared their experiences and perceptions of clinical academic research activities. Findings: Three major themes were identified related to the perceived benefits, barriers and enablers of engagement in these career pathways: Building health research capacity; Building individuals’ health research capability; and Improving patient care. Conclusion: This report demonstrates factors that are valued and perceived to be working well by practitioners and their clinical service managers, and highlights key priorities for further strategic support

Exploring blog narratives of parental loneliness: A thematic network analysis

UK-based national surveys and international longitudinal studies have shown that around a third of parents experience chronic or persistent loneliness. There is limited research about the experience of loneliness in parenthood, however blogs authored by parents, sharing their personal experiences about loneliness offer a potential rich data source. The purpose of this study was to identify and analyse blog narratives written by parents who had experienced loneliness to increase understanding of their experiences. One hundred and ninety-six relevant blog posts were identified, of which 157 had contact details to request permission to use the blog post in the study. Twenty-two parent bloggers gave their permission. Thematic network analysis was used to open code the blogs and 4 organising themes and subthemes emerged, which centred on a global theme of disconnection. Disconnection underpinned themes relating to a sense that being a parent was overwhelming, changes in identity linked to becoming a parent, difficulties in sharing feelings of loneliness with others, and a need for social connection. Findings point to parents being unprepared for the transition to parenthood, with implications for perinatal education and support, including further opportunities for parents to connect to reduce social isolation

Quantification of Extracellular DNA Network Abundance and Architecture within Streptococcus gordonii Biofilms Reveals Modulatory Factors

Extracellular DNA (eDNA) is an important component of biofilm matrix that serves to maintain biofilm structural integrity, promotes genetic exchange within the biofilm, and provides protection against antimicrobial compounds. Advances in microscopy techniques have provided evidence of the cobweb- or lattice-like structures of eDNA within biofilms from a range of environmental niches. However, methods to reliably assess the abundance and architecture of eDNA remain lacking. This study aimed to address this gap by development of a novel, high-throughput image acquisition and analysis platform for assessment of eDNA networks in situ within biofilms. Utilizing Streptococcus gordonii as the model, the capacity for this imaging system to reliably detect eDNA networks and monitor changes in abundance and architecture (e.g., strand length and branch number) was verified. Evidence was provided of a synergy between glucans and eDNA matrices, while it was revealed that surface-bound nuclease SsnA could modify these eDNA structures under conditions permissive for enzymatic activity. Moreover, cross talk between the competence and hexaheptapeptide permease systems was shown to regulate eDNA release by S. gordonii. This novel imaging system can be applied across the wider field of biofilm research, with potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit. IMPORTANCE Extracellular DNA (eDNA) is critical for maintaining the structural integrity of many microbial biofilms, making it an attractive target for the management of biofilms. However, our knowledge and targeting of eDNA are currently hindered by a lack of tools for the quantitative assessment of eDNA networks within biofilms. Here, we demonstrate use of a novel image acquisition and analysis platform with the capacity to reliably monitor the abundance and architecture of eDNA networks. Application of this tool to Streptococcus gordonii biofilms has provided new insights into how eDNA networks are stabilized within the biofilm and the pathways that can regulate eDNA release. This highlights how exploitation of this novel imaging system across the wider field of biofilm research has potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit

SCOPE New Photographic Practices

The photographic practices brought together for this exhibition and publication provide a broad scope of how photographic and lens based media may be used in order to have a visceral and conceptual impact. The methods on show demonstrate the way that artists might pick and choose from the approaches, processes and debates that have arisen through the medium’s history. This collection of work features film, video and photography that demand a renegotiation of the relationship between camera, subject and viewer. Visual Art Centre Gallery, Tsinghua University, Beijing, Chin

Feasibility of a complex behaviour change intervention in secondary care to safely and substantially reduce antibiotic use

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