Evaluation of State-Led Surveillance of Neonatal Abstinence Syndrome - Six U.S. States, 2018-2021.

Opioid use disorder (OUD) is a significant public health problem in the United States, which affects children as well as adults. During 2010-2017, maternal opioid-related diagnoses increased approximately 130%, from 3.5 to 8.2 per 1,000 hospital deliveries, and neonatal abstinence syndrome (NAS) increased 83%, from 4.0 to 7.3 per 1,000 hospital deliveries (1). NAS, a withdrawal syndrome, can occur among infants following in utero exposure to opioids and other psychotropic substances (2). In 2018, a study of six states with mandated NAS case reporting for public health surveillance (2013-2017) found that mandated reporting helped quantify NAS incidence and guide programs and services (3). To review surveillance features and programmatic development in the same six states, a questionnaire and interview with state health department officials on postimplementation efforts were developed and implemented in 2021. All states reported ongoing challenges with initial case reporting, limited capacity to track social and developmental outcomes, and no requirement for long-term follow-up in state-mandated case reporting; only one state instituted health-related outcomes monitoring. The primary surveillance barrier beyond initial case reporting was lack of infrastructure. To serve identified needs of opioid- or other substance-exposed mother-infant dyads, state health departments reported programmatic successes expanding education and access to maternal medication for opioid use disorder (MOUD), community and provider education or support services, and partnerships with perinatal quality collaboratives. Development of additional infrastructure is needed for states aiming to advance NAS surveillance beyond initial case reporting.

Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT).

AIM: To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial). METHODS: Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m2 , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA1c <48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2 ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss. RESULTS: Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission. CONCLUSIONS: Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.

The Role of Antiseptic Irrigation Solutions and Topical Antibiotics in Total Joint Arthroplasty.

Prosthetic joint infections (PJI) are devastating complications. Antiseptic irrigation fluids have shown promising in vitro results in eradicating planktonic bacteria and decreasing biofilm burden. Topical antibiotics, specifically vancomycin, represents another potentially cost-effective way to prevent acute postoperative PJI. We provide a review of the current literature and recommendations on these measures. Overall, a current lack of high-powered, prospective studies exists to definitively support the use of any specific antiseptic solution or topical antibiotic in primary or revision total joint arthroplasty. Some studies support the use of dilute povidone-iodine lavage when combined with vancomycin powder. Data also exists to support the cost effectiveness of povidone-iodine, with the necessary risk reduction to justify its cost. Contradictory evidence exists demonstrating no differences in PJI rates with these measures and possibly higher rates of aseptic wound complications associated with vancomycin power. Further study is warranted. (Journal of Surgical Orthopaedic Advances 30(4):226-230, 2021).

First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

Can type 2 diabetes be reversed and how can this best be achieved? James Lind Alliance research priority number one.

The James Lind Alliance, in association with Diabetes UK, conducted a survey of people with Type 2 diabetes to establish their priorities for research. The number one research priority was found to be 'Can Type 2 diabetes be cured or reversed, what is the best way to achieve this, and is there a point beyond which the condition cannot be reversed?'. The present review summarizes the current understanding of weight loss-induced reversal of Type 2 diabetes. It considers the diagnostic criteria for remission and describes the clinical features of post-diabetes. It is of great importance to recognize these, as post-diabetes differs considerably from the high cardiovascular risk state of prediabetes. Current data demonstrate long-term stable ß-cell function, providing weight regain is prevented. If an individual, having previously demonstrated susceptibility to Type 2 diabetes, returns to their previous weight then recurrence of the condition is certain. Appropriate use of the terms 'reversal' and 'remission' is discussed, with emphasis that the word 'cure' is inappropriate. Evidence-based means of achieving and maintaining remission of Type 2 diabetes are described, together with a summary of the information on the steadily diminishing chance of achieving reversal with increasing duration of Type 2 diabetes.

Views, experience and adherence among pregnant women with gestational diabetes participating in a weight loss study (WELLBABE).

AIMS: To investigate the views and experience of pregnant women newly diagnosed with gestational diabetes mellitus participating in a 1200 kcal/day diet to achieve moderate weight loss (the WELLBABE study), and to explore barriers to and facilitators of adherence. METHODS: Twelve participants engaged in semi-structured interviews after completion of the 4-week diet. An interview schedule was devised using open-ended questions guided by the Theoretical Domains Framework. Transcript responses were analysed thematically. RESULTS: Participants were anxious about their diagnosis of gestational diabetes, but concerns related to dieting in pregnancy were allayed by reassurance from the research team. Participants expected health benefits, improved knowledge and support from enrolling on the study. The participants' primary motivator to diet adherence was their baby's wellbeing. Other facilitatory factors included improving their own health and reducing any future risk of diabetes. Trying to provide reliable results and receiving extra care also facilitated adherence. Partners, friends and family were an important source of social support and no barrier caused by concern about weight loss in pregnancy was encountered. Observed and experienced physical changes and feedback from the research team positively reinforced adherence. The main barrier was that learning new skills was initially time-consuming. CONCLUSIONS: Weight loss was acceptable to women with gestational diabetes provided with clear information about likely benefit. A randomized controlled trial of this intervention is now required, employing clear information and feedback of glycaemic benefit to facilitate efficacy.

Epizootics of Streptococcus agalactiae infection in captive rays from Queensland, Australia.

The aim of this study was to describe two epizootics of high mortalities from infection with Streptococcus agalactiae, occurring in captive rays held in a marine display aquarium in south-east Queensland, Australia, in 2009 and 2010. Five different species of rays were affected, including mangrove whiprays (Himantura granulata), estuary rays (Dasyatis fluviorum), eastern shovelnose rays (Aptychotrema rostrata), white-spotted eagle rays (Aetobatus narinari) and blue-spotted mask rays (Neotrygon kuhlii). This report describes the history of both epizootics including collection, quarantine and husbandry of rays, the disease epizootics, clinico-pathological features of the disease, antimicrobial therapy, autogenous vaccine production, and laboratory studies including clinical and histopathology, bacteriology, PCR, molecular serotyping and sequencing of the bacterium S. agalactiae.

Mothers and teenage daughters walking to health: using the behaviour change wheel to develop an intervention to improve adolescent girls' physical activity.

OBJECTIVES: The majority of adolescent girls fail to meet public health guidelines for physical activity. Engaging mothers in the promotion of physical activity for their daughters may be an important strategy to facilitate behaviour change. The aim of this study was to use the behaviour change wheel (BCW) framework to design the components of an intervention to improve adolescent girls' physical activity. STUDY DESIGN: Cross-sectional study to inform intervention development. METHODS: The BCW framework was used to (1) understand the behaviour, (2) identify intervention functions and (3) select content and implementation options. A circular development process was undertaken by the research team to collectively design the intervention in accordance with the steps recommended by the BCW. RESULTS: The BCW design process resulted in the selection of six intervention functions (education, persuasion, incentivization, training, modelling, enablement) and 18 behaviour change techniques delivered via group-based, face-to-face mode. Behaviour change technique groupings include: goals and planning; feedback and monitoring; social support; shaping knowledge; natural consequences; comparison of behaviour; associations; comparison of outcomes; reward and threat; identity; and, self-belief. CONCLUSIONS: The BCW process allowed an in-depth consideration of the target behaviours and provided a systematic framework for developing the intervention. The feasibility and preliminary efficacy of the programme will be examined.

Multistate outbreak of Listeria monocytogenes infections linked to whole apples used in commercially produced, prepackaged caramel apples: United States, 2014-2015.

Whole apples have not been previously implicated in outbreaks of foodborne bacterial illness. We investigated a nationwide listeriosis outbreak associated with caramel apples. We defined an outbreak-associated case as an infection with one or both of two outbreak strains of Listeria monocytogenes highly related by whole-genome multilocus sequence typing (wgMLST) from 1 October 2014 to 1 February 2015. Single-interviewer open-ended interviews identified the source. Outbreak-associated cases were compared with non-outbreak-associated cases and traceback and environmental investigations were performed. We identified 35 outbreak-associated cases in 12 states; 34 (97%) were hospitalized and seven (20%) died. Outbreak-associated ill persons were more likely to have eaten commercially produced, prepackaged caramel apples (odds ratio 326·7, 95% confidence interval 32·2-3314). Environmental samples from the grower's packing facility and distribution-chain whole apples yielded isolates highly related to outbreak isolates by wgMLST. This outbreak highlights the importance of minimizing produce contamination with L. monocytogenes. Investigators should perform single-interviewer open-ended interviews when a food is not readily identified.

International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder - USA and Canada, 2013-2014.

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

Infection and pathology in Queensland grouper, Epinephelus lanceolatus, (Bloch), caused by exposure to Streptococcus agalactiae via different routes.

Since 2007, 96 wild Queensland groupers, Epinephelus lanceolatus, (Bloch), have been found dead in NE Australia. In some cases, Streptococcus agalactiae (Group B Streptococcus, GBS) was isolated. At present, a GBS isolate from a wild grouper case was employed in experimental challenge trials in hatchery-reared Queensland grouper by different routes of exposure. Injection resulted in rapid development of clinical signs including bilateral exophthalmia, hyperaemic skin or fins and abnormal swimming. Death occurred in, and GBS was re-isolated from, 98% fish injected and was detected by PCR in brain, head kidney and spleen from all fish, regardless of challenge dose. Challenge by immersion resulted in lower morbidity with a clear dose response. Whilst infection was established via oral challenge by admixture with feed, no mortality occurred. Histology showed pathology consistent with GBS infection in organs examined from all injected fish, from fish challenged with medium and high doses by immersion, and from high-dose oral challenge. These experimental challenges demonstrated that GBS isolated from wild Queensland grouper reproduced disease in experimentally challenged fish and resulted in pathology that was consistent with that seen in wild Queensland grouper infected with S. agalactiae.

Predictors of fuel poverty and the equity of local fuel poverty support: secondary analysis of data from Bradford, England.

AIMS: Addressing fuel poverty is a critical public health issue given its recent rise in prevalence across Europe. Although previous research identifies national risk markers of fuel poverty, evidence is lacking on whether these are consistent across local geographies, and the equity of local interventions. In the UK's current economic climate, it is more crucial than ever that services benefit households in greatest need. This study aimed to determine significant predictors of fuel poverty among households in Bradford, England, comparing them to national-level predictors, and evaluate if households possessing significant fuel poverty predictors were equitably referred to a local fuel poverty service (Warm Homes Healthy People, WHHP). METHODS: A multivariate logistic regression model determined significant fuel poverty predictors in Bradford using household-level data from the Energy Saving Trust and the Low Income High Costs fuel poverty definition. Statistical testing highlighted significant differences in predictors of fuel poverty between households referred to WHHP and all Bradford households. RESULTS: Significant (p < .05) predictors of fuel poverty included: living in an area with lower average household incomes and higher proportion of ethnic minority individuals, and living in a property with a lower energy efficiency rating. Households living in a detached or older property, and homeowners were more likely to be fuel poor. Differences in the direction of the relationship with fuel poverty were identified between some national and local predictors. Most predictors were significantly (p < .05) overrepresented among WHHP households, suggesting equitable service reach. Ethnic minorities, younger people, and multiperson households were underrepresented. CONCLUSIONS: Local fuel poverty predictors were similar to many national-level predictors, but identified differences in the direction of the relationship between some national and local predictors reaffirm the value of locally focused research. WHHP successfully targeted households possessing key predictors, but should ensure that ethnic minorities, younger people, and multiperson households are equitably referred.

AI implementation in the UK landscape: Knowledge of AI governance, perceived challenges and opportunities, and ways forward for radiographers.

INTRODUCTION: Despite the rapid increase of AI-enabled applications deployed in clinical practice, many challenges exist around AI implementation, including the clarity of governance frameworks, usability of validation of AI models, and customisation of training for radiographers. This study aimed to explore the perceptions of diagnostic and therapeutic radiographers, with existing theoretical and/or practical knowledge of AI, on issues of relevance to the field, such as AI implementation, including knowledge of AI governance and procurement, perceptions about enablers and challenges and future priorities for AI adoption. METHODS: An online survey was designed and distributed to UK-based qualified radiographers who work in medical imaging and/or radiotherapy and have some previous theoretical and/or practical knowledge of working with AI. Participants were recruited through the researchers' professional networks on social media with support from the AI advisory group of the Society and College of Radiographers. Survey questions related to AI training/education, knowledge of AI governance frameworks, data privacy procedures, AI implementation considerations, and priorities for AI adoption. Descriptive statistics were employed to analyse the data, and chi-square tests were used to explore significant relationships between variables. RESULTS: In total, 88 valid responses were received. Most radiographers (56.6 %) had not received any AI-related training. Also, although approximately 63 % of them used an evaluation framework to assess AI models' performance before implementation, many (36.9 %) were still unsure about suitable evaluation methods. Radiographers requested clearer guidance on AI governance, ample time to implement AI in their practice safely, adequate funding, effective leadership, and targeted support from AI champions. AI training, robust governance frameworks, and patient and public involvement were seen as priorities for the successful implementation of AI by radiographers. CONCLUSION: AI implementation is progressing within radiography, but without customised training, clearer governance, key stakeholder engagement and suitable new roles created, it will be hard to harness its benefits and minimise related risks. IMPLICATIONS FOR PRACTICE: The results of this study highlight some of the priorities and challenges for radiographers in relation to AI adoption, namely the need for developing robust AI governance frameworks and providing optimal AI training.

Speed of facial affect intensity recognition as an endophenotype of first-episode psychosis and associated limbic-cortical grey matter systems.

BACKGROUND: Psychotic disorders are highly heritable such that the unaffected relatives of patients may manifest characteristics, or endophenotypes, that are more closely related to risk genes than the overt clinical condition. Facial affect processing is dependent on a distributed cortico-limbic network that is disrupted in psychosis. This study assessed facial affect processing and related brain structure as a candidate endophenotype of first-episode psychosis (FEP). METHOD: Three samples comprising 30 FEP patients, 30 of their first-degree relatives and 31 unrelated healthy controls underwent assessment of facial affect processing and structural magnetic resonance imaging (sMRI) data. Multivariate analysis (partial least squares, PLS) was used to identify a grey matter (GM) system in which anatomical variation was associated with variation in facial affect processing speed. RESULTS: The groups did not differ in their accuracy of facial affect intensity rating but differed significantly in speed of response, with controls responding faster than relatives, who responded faster than patients. Within the control group, variation in speed of affect processing was significantly associated with variation of GM density in amygdala, lateral temporal cortex, frontal cortex and cerebellum. However, this association between cortico-limbic GM density and speed of facial affect processing was absent in patients and their relatives. CONCLUSIONS: Speed of facial affect processing presents as a candidate endophenotype of FEP. The normal association between speed of facial affect processing and cortico-limbic GM variation was disrupted in FEP patients and their relatives.

Identification of a biological signature for schizophrenia in serum.

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of ~50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms.

Farmer decision-making and risk perceptions towards outwintering cattle.

Increasing financial pressures has led farmers to manage cattle outside for the winter months. In temperate areas the environmental risks of outwintering cattle are exacerbated by cooler and wetter weather and identifying how farmers perceive these risks is essential to understanding how potential hazards could be mitigated. A series of workshops were conducted with cattle producers in England and Wales to understand their perceptions of the risks, their decision-making with respect to outwintering and their options for mitigating these risks. A range of risks were identified, but emphasis was placed on environmentally-related risks, such as soil damage, and on social risks, such as public perception of their treatment of the animals. The uncertainties due to the weather were highlighted as the most unmanageable risk. Another significant barrier to mitigating environmental impacts emerged from the lack of options towards choosing appropriate fields in which to conduct outwintering. We argue that the farmer-led nature of outwintering and the development of a wide range of systems is evidence of outwintering being a systems-innovation. We conclude that there is a role for Government intervention through the provision of information which clarifies cross-compliance breaches, but also encourages farmer-led innovation to develop more responsive outwintering systems.

Examining factors for the adoption of silvopastoral agroforestry in the Colombian Amazon.

Current land use systems in the Amazon largely consist of extensive conventional productivist livestock operations that drive deforestation. Silvopastoral systems (SPS) support a transition to low carbon production if they intensify in sympathy with the needs of biophysical and socio-economic contexts. SPS have been promoted for decades as an alternative livestock production system but widespread uptake has yet to be seen. We provide a schema of associating factors for adoption of SPS based on past literature in tropical agriculture and apply this to a bespoke survey of 172 farms in the Caquetá region of the Colombian Amazon. We find a number of factors which do not apply to this region and argue for a context specific approach. The impact of managing increased market access and opportunities for SPS producers are crucial to avoiding additional deforestation. Further understanding of the underlying antecedents of common factors, such as perceptions of silvopastoral systems, would reduce the risk of perverse policy outcomes.

Functional immune boosters; the herb or its dead microbiome? Antigenic TLR4 agonist MAMPs found in 65 medicinal roots and algae's.

Background: Humans have been consuming medicinal plants (as herbs/ spices) to combat illness for centuries while ascribing beneficial effects predominantly to the plant/phytochemical constituents, without recognizing the power of obligatory resident microorganism' communities (MOCs) (live/dead bacteria, fungus, yeast, molds etc.) which remain after industrial microbial reduction methods. Very little is known about the taxonomic identity of residual antigenic microbial associated molecular patterns (MAMPs) debris in our botanical over the counter (OTC) products, which if present would be recognized as foreign (non-self) antigenic matter by host pattern recognition receptors (PRRs) provoking a host immune response; this the basis of vaccine adjuvants. As of today, only few research groups have removed the herbal MAMP biomass from herbs, all suggesting that immune activation may not be from the plant but rather its microbial biomass; a hypothesis we corroborate. Purpose: The purpose of this work was to conduct a high through put screening (HTPS) of over 2500 natural plants, OTC botanical supplements and phytochemicals to elucidate those with pro-inflammatory; toll like receptor 4 (TLR4) activating properties in macrophages. Study Design: The HTPS was conducted on RAW 264.7 cells vs. lipopolysaccharide (LPS) E. coli 0111:B4, testing iNOS / nitric oxide production (NO2-) as a perimeter endpoint. The data show not a single drug/chemical/ phytochemical and approximately 98 % of botanicals to be immune idle (not effective) with only 65 pro-inflammatory (hits) in a potency range of LPS. Method validation studies eliminated the possibility of false artifact or contamination, and results were cross verified through multiple vendors/ manufacturers/lot numbers by botanical species. Lead botanicals were evaluated for plant concentration of LPS, 1,3:1,6-ß-glucan, 1,3:1,4-ß-D-glucan and α-glucans; where the former paralleled strength in vitro. LPS was then removed from plants using high-capacity endotoxin poly lysine columns, where bioactivity of LPS null "plant" extracts were lost. The stability of E.Coli 0111:B4 in an acid stomach mimetic model was confirmed. Last, we conducted a reverse culture on aerobic plate counts (APCs) from select hits, with subsequent isolation of gram-negative bacteria (MacConkey agar). Cultures were 1) heat destroyed (retested/ confirming bioactivity) and 2) subject to taxonomical identification by genetic sequencing 18S, ITS1, 5.8 s, ITS2 28S, and 16S. Conclusion: The data show significant gram negative MAMP biomass dominance in A) roots (e.g. echinacea, yucca, burdock, stinging nettle, sarsaparilla, hydrangea, poke, madder, calamus, rhaponticum, pleurisy, aconite etc.) and B) oceanic plants / algae's (e.g. bladderwrack, chlorella, spirulina, kelp, and "OTC Seamoss-blends" (irish moss, bladderwrack, burdock root etc), as well as other random herbs (eg. corn silk, cleavers, watercress, cardamom seed, tribulus, duckweed, puffball, hordeum and pollen). The results show a dominance of gram negative microbes (e.g. Klebsilla aerogenes, Pantoae agglomerans, Cronobacter sakazakii), fungus (Glomeracaea, Ascomycota, Irpex lacteus, Aureobasidium pullulans, Fibroporia albicans, Chlorociboria clavula, Aspergillus_sp JUC-2), with black walnut hull, echinacea and burdock root also containing gram positive microbial strains (Fontibacillus, Paenibacillus, Enterococcus gallinarum, Bromate-reducing bacterium B6 and various strains of Clostridium). Conclusion: This work brings attention to the existence of a functional immune bioactive herbal microbiome, independent from the plant. There is need to further this avenue of research, which should be carried out with consideration as to both positive or negative consequences arising from daily consumption of botanicals highly laden with bioactive MAMPS.

Rare and declining bird species benefit most from designating protected areas for conservation in the UK.

There have been recent renewed commitments to increase the extent of protected areas to combat the growing biodiversity crisis but the underpinning evidence for their effectiveness is mixed and causal connections are rarely evaluated. We used data gathered by three large-scale citizen science programmes in the UK to provide the most comprehensive assessment to date of whether national (Sites of Special Scientific Interest) and European (Special Protection Areas/Special Areas of Conservation) designated areas are associated with improved state (occurrence, abundance), change (rates of colonization, persistence and trend in abundance), community structure and, uniquely, demography (productivity) on a national avifauna, while controlling for differences in land cover, elevation and climate. We found positive associations with state that suggest these areas are well targeted and that the greatest benefit accrued to the most conservation-dependent species since positive associations with change were largely restricted to rare and declining species and habitat specialists. We suggest that increased productivity provides a plausible demographic mechanism for positive effects of designation.

Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix.

Deficiency of any component of the ER-resident collagen prolyl 3-hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7-year-old Egyptian boy with non-lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3-hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3-hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long-term cultures, we identified a severe deficiency (10-15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse-chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI.