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Abstract Background Prokaryotic microbes have impacted marine biogeochemical cycles for billions of years. Viruses also impact these cycles, through lysis, horizontal gene transfer, and encoding and expressing genes that contribute to metabolic reprogramming of prokaryotic cells. While this impact is difficult to quantify in nature, we hypothesized that it can be examined by surveying virus-encoded auxiliary metabolic genes (AMGs) and assessing their ecological context. Results We systematically developed a global ocean AMG catalog by integrating previously described and newly identified AMGs and then placed this catalog into ecological and metabolic contexts relevant to ocean biogeochemistry. From 7.6 terabases of Tara Oceans paired prokaryote- and virus-enriched metagenomic sequence data, we increased known ocean virus populations to 579,904 (up 16%). From these virus populations, we then conservatively identified 86,913 AMGs that grouped into 22,779 sequence-based gene clusters, 7248 (~ 32%) of which were not previously reported. Using our catalog and modeled data from mock communities, we estimate that ~ 19% of ocean virus populations carry at least one AMG. To understand AMGs in their metabolic context, we identified 340 metabolic pathways encoded by ocean microbes and showed that AMGs map to 128 of them. Furthermore, we identified metabolic “hot spots” targeted by virus AMGs, including nine pathways where most steps (≥ 0.75) were AMG-targeted (involved in carbohydrate, amino acid, fatty acid, and nucleotide metabolism), as well as other pathways where virus-encoded AMGs outnumbered cellular homologs (involved in lipid A phosphates, phosphatidylethanolamine, creatine biosynthesis, phosphoribosylamine-glycine ligase, and carbamoyl-phosphate synthase pathways). Conclusions Together, this systematically curated, global ocean AMG catalog and analyses provide a valuable resource and foundational observations to understand the role of viruses in modulating global ocean metabolisms and their biogeochemical implications. Video Abstract

Through a behavioural coordination game played by groups of humans and simulated with agent-based models, we investigated a social network dilemma that we call fraughtness. Seven players, connected to one another in various topologies via a computer network, each had to move a slider to the left or right along a horizontal bar on their screen. The goal was for all the players to move their slider to the same side. Players received feedback indicating the degree to which they and their neighbours agreed about the choice of side. When the topology had a hierarchical branching structure, the groups often got stuck in fraughtness: players on one branch favoured one side, while players on the other branch favoured the other; because all were receiving supportive local feedback, nobody wanted to change. Nevertheless, after being stuck in fraughtness for some time, most groups managed to escape it. Fraughtness is arguably an analog of generally negatively viewed social phenomena like polarization and echo chambers. Our analyses suggest that while fraughtness is problematic, it is closely linked to successful structure formation—it thus may be most effective to focus not on how to banish it, but on how to resolve it.

Abstract Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.

Introduction and objective: Bladder neck contracture is an uncommon yet problematic adverse event following BPH surgery. In its most severe form, complete outlet obliteration can result. In the face of a long segment obliteration, reconstruction may involve a urethral ‘pull-through’ technique, or alternatively, excision of the intervening segment with primary urethrovesical anastomosis; this may require additional maneuvers such as partial prostatectomy. Recently, a robotic-assisted laparoscopic (RAL) subtrigonal inlay of buccal mucosal graft was described for bladder neck reconstruction in the setting of refractory contracture formation. We elaborate on this technique with the addition of an advancement bladder flap to form the anterior plate, opposing a posteriorly positioned buccal mucosal graft, for the treatment of complete prostatic urethral obliteration. Methods: A 71-year old male with a history of BPH and detrusor underactivity presented after open simple prostatectomy with urinary retention and bilateral hydronephrosis. Bladder emptying was managed with a suprapubic tube. Retrograde urethrogram (RUG)/voiding cystourethrogram (VCUG) demonstrated complete obliteration from the bladder neck through the prostatic urethra. The patient underwent a RAL reconstruction with buccal mucosal graft and advancement bladder flap without intraoperative complication. There was no perineal incision or open conversion. Results: The patient was discharged on postoperative day 1. His-urethral catheter was removed at 1 month, and RUG/VCUG showed no obstruction or extravasation. He voids spontaneously with large residual volumes, for which he performs nightly clean intermittent catheterization. Cystoscopy at most recent follow-up demonstrated patency and a well-healed posterior buccal graft and anterior advancement bladder flap. Conclusions: We describe one option for repairing prostatic urethral obliteration which utilizes a posterior buccal mucosal graft inlay and an anterior advancement bladder flap. Perineal dissection and urethral transection is avoided, thus preserving urethral blood supply by not compromising the bulbar artery. Additionally, it avoids extirpative surgery with attendant risks of erectile dysfunction and urinary incontinence.

This study on the person-organization fit theory, measured in terms of value congruence, explored qualitative data from a survey of non-managerial retail employees in a Northwestern state in the United States in relation to job satisfaction and employee-organization value congruence in a retail establishment that has shown a remarkable deviation from the norm with employee turnover far below what is obtainable in the retail industry. The results of a field study of 18 employees, through open ended interviews and survey transcripts, analyzed thematically using Nvivo qualitative data analysis tool, identified five themes that influence job satisfaction and employee retention: Friendly workplace environment, Flexibility, Stability, Management Support, and Independence.

Introduction International research suggests free online postal self-sampling for sexually transmitted infection (STI) testing is an acceptable alternative to clinic-based testing. A user-pays online STI testing service exists in Aotearoa New Zealand, but acceptability among priority populations is unknown. Aim To explore Māori and Pacific young people's perspectives on online postal self-sampling for STI testing (as prospective service users). Methods Four wānanga (knowledge-sharing forum) were held between November 2022 and May 2023 with Māori and Pacific participants aged 15-24 years who were recruited via youth-focused community organisations. Three facilitators guided discussions about STI testing and use of an online service. Inductive thematic analysis was used to analyse data generated from audio-recorded discussions, group work notes and facilitator field notes. Results None of the 38 participants were aware of online STI testing and all considered it cost-prohibitive. Perceptions of online testing were mixed, and discussion about concerns outweighed perceived benefits. Three themes were identified: (i) potential to support autonomy (perceived benefits and positive features of self-sample collection kits); (ii) barriers and process-related concerns; and (iii) tailoring online STI testing to young people's needs (facilitating engagement with online testing). Discussion For online STI testing to be an accessible alternative to clinic-based testing for priority populations, cost, low awareness and other barriers in the testing pathway need to be addressed. Clinician follow-up on positive results and free treatment would be critical to ensure the cycle of best practice care is completed. Regardless of where testing is accessed, investment is needed to support young people's knowledge of when, why and how to access a sexual health check.

Introduction Gender affirming hormone therapy (GAHT) is an important aspect of health care for many transgender and non-binary (TNB) people, but little is known about the long-term outcomes for TNB people in Aotearoa New Zealand (NZ). Pathways to access GAHT are shifting from secondary care towards primary care, so this is an opportune time to commence local research on long-term health and wellbeing outcomes for people initiating GAHT. Aim This paper aims to report on the key findings from four meetings held to inform the design of a prospective cohort study to follow the journey of people initiating GAHT in primary and secondary care settings in NZ. Methods We worked with a community advisory group of six TNB young people and sought input from 14 health care providers involved in the care of TNB people initiating GAHT (GPs, secondary care doctors, and mental health providers). Semi-structured interview schedules were used to guide discussions. Template analysis was used to initially code data based on themes identified from the interview schedule and new themes from discussions were added. Results Participants shared ideas about recruitment and data collection priorities for baseline and follow-up surveys. These included understanding the journey to starting hormone therapy (information-seeking, decision-making), access to services for GAHT initiation, appropriateness of information provision, receipt of the first prescription, goals for and experience of GAHT, and the unique needs of non-binary people. Discussion Input from a TNB advisory group and health care professionals has informed the development of a survey that will be used to understand the experience of, and outcomes for, people starting GAHT in NZ. Findings from this planned prospective cohort study have the potential to improve access to GAHT for TNB people who wish to pursue this option.

Background: Rainbow young people (RYP; people of diverse genders, sexualities, and variations in sex characteristics) face barriers accessing primary care, often report negative experiences and the need to educate clinicians on rainbow-specific issues. This study explores general practice staff views and experiences of providing care to RYP., Methods: Three focus groups were held with staff from 5 general practices in an urban area of Aotearoa New Zealand (25 participants in total). Practices were purposively selected to include some known to be more "rainbow-friendly" seeing larger numbers of RYP and some with no particular focus on RYP. All members of each practice were invited to participate, including administration and reception staff. Focus groups were audio-recorded, transcribed, and analysed in NVivo using inductive thematic analysis., Results: Four main themes were identified: (i) Practice experience, (ii) Feeling awkward, (iii) Knowledge and training, and (iv) Structural barriers. Differences were apparent in health provider knowledge, comfort, and experience in providing care to RYP. Participants identified a lack of knowledge and training and wanted more resources and education. Systems limitations were common (e.g. with IT systems for recording gender) and often contributed to awkward clinical encounters., Conclusions: Participants recognized shortcomings in their training, knowledge, and level of confidence providing care to RYP and expressed a desire to improve their competency. Further work is needed to identify and trial practical strategies that help improve communication skills, knowledge, and the delivery of more equitable healthcare to RYP., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Mental distress is on the rise for young people, and there are high levels of unmet need for support. Increasingly, young people are engaging with online mechanisms of support to avoid cost and wait times; however, online support does have its limitations. We surveyed young people, 15-30 years of age, in Aotearoa New Zealand to explore their views of digital support for mental health. The aim of this study was to find out from young people what they thought about various types of online support and perceived benefits and drawbacks., Methods: A cross-sectional online survey promoted through social media advertising was used. Participants included anyone aged 15-30 years living in Aotearoa New Zealand. The survey ran for 10 weeks between February and May 2022. It included demographic questions and asked about (i) use of digital support for mental health; (ii) what digital support is best used for; (iii) best ways of publicising mental health supports to young people; and (iv) where they would choose to get information about mental health support. Questions were a mix of forced choice and free text. Participants could opt to take part in a follow-up interview., Results: Surveys were completed by 1471 participants; two respondents participated in an interview. A total of 641 participants had used digital support before (44%). The most used forms of digital support were websites (n = 324) and watching videos (n = 260), although these were not necessarily rated as the most helpful. Alternatives that people most wanted to try were podcasts and phone or video consultations with a counsellor or therapist. Drawbacks of digital support included privacy concerns, technical issues, lack of quality and motivation requirements. Benefits included ease of access, anonymity and a non-threatening starting point., Conclusions: Digital support has a place in mental health care, but strong sentiment was expressed in favour of real-life support. It may also be worth investing in more innovative types of digital support such as online performing arts and podcasts., Patient or Public Contribution: A group of young people were recruited as co-researchers, had input into survey design, data analysis and interpretation and are co-authors (list of co-authors). Survey respondents also included young people with lived experience who are members of the general public., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Competing Interests: The authors have no conflicts of interest to declare. Data are not publicly available. Study participants were not asked for permission, and nor was ethical approval granted for data to be shared publicly.

Background: Māori and Pacific young people are disproportionately impacted by sexually transmitted infections (STIs). Access to STI screening is important to reduce transmission and reproductive health complications., Methods: Between November 2022 and May 2023, we held four wānanga (workshops) with Māori and Pacific participants (15-24years old) to find out what barriers they encounter to STI testing, and hear their ideas about how to overcome these. Participants were recruited via youth-focused community organisations in the Wellington region of Aotearoa New Zealand. Inductive thematic analysis was used to understand data generated from discussions, drawing on Māori and Pacific models of wellbeing to frame themes., Results: Thirty-eight participants were involved in the wānanga. Barriers to STI testing related to five themes: (1) differences in cultural values and expression; (2) family/friends; (3) educational gaps; (4) psychological factors; and (5) structural obstacles. Suggested strategies to improve access to sexual health care included the need for free, flexible services, education and health promotion activities to reach young people in their spaces (e.g. church, marae, social media). Participants stressed the need for approaches to be community-based, delivered by trusted individuals using culturally appropriate messages, and saw participation in STI testing as beneficial for whānau/family and communities., Conclusions: To improve access to STI testing, participants described the need for free services, together with education and health promotion to improve inter-generational sexual health knowledge. Reframing messages around STIs to align with Māori and Pacific models of wellbeing was identified as a way to normalise conversations, in turn reducing the stigma surrounding STI testing.

Background: Telehealth became more widely used when the global COVID-19 pandemic restricted access to in-person consultations for primary care during periods of 'lockdown'., Methods: In 2021 (August-September), 15-to 25-year-olds in the Wellington region of Aotearoa New Zealand were invited to participate in an online survey that aimed to find out about telehealth experiences, perceived advantages and disadvantages, and willingness to use it for receipt of primary care., Results: Surveys were completed by 346 participants, 133 of whom had ever used telehealth (38%). Overall, 73% (84/115) were happy with health care received via telehealth, but only 26% preferred it to in-person consultations. Perceived benefits related to convenience and time efficiency, but participants had concerns about the inability to be physically examined, technological issues, clarity around follow-up actions, payment and lack of privacy. All participants had access to a phone or device, yet almost half reported challenges with connectivity, coverage or data that might limit their ability to access telehealth (47.3%, 159/336). Half of participants wanted to use telehealth in future (preferring phone over video (160/315))., Conclusions: Young people surveyed acknowledged the convenience of telehealth, but many were hesitant about receiving primary care in this way. Understanding young people's reservations and provision of detailed information about what telehealth entails will help prepare and support them to use telehealth in future.

Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth factor-II (IGF-II) is overexpressed in lung tissues and fibroblasts from SSc patients, and IGF-II fosters fibrosis by upregulating collagen type I, fibronectin, and TGFβ. We now show that IGF-II augments mRNA levels of profibrotic signaling molecules TGFβ2 ( p ≤ 0.01) and TGFβ3 ( p ≤ 0.05), collagen type III ( p ≤ 0.01), and the collagen posttranslational modification enzymes P4HA2 ( p ≤ 0.05), P3H2 ( p ≤ 0.05), LOX ( p = 0.065), LOXL2 ( p ≤ 0.05), LOXL4 ( p ≤ 0.05) in primary human lung fibroblasts. IGF-II increases protein levels of TGFβ2 ( p ≤ 0.01), as well as COL3A1, P4HA2, P4Hβ, and LOXL4 ( p ≤ 0.05). In contrast, IGF-II decreases mRNA levels of the collagen degradation enzymes cathepsin (CTS) K, CTSB , and CTSL and protein levels of CTSK ( p ≤ 0.05). The SRY-box transcription factor 9 (SOX9) is overexpressed in SSc lung tissues at the mRNA ( p ≤ 0.05) and protein ( p ≤ 0.01) levels compared to healthy controls. IGF-II induces SOX9 in lung fibroblasts ( p ≤ 0.05) via the IGF1R/IR hybrid receptor, and SOX9 regulates TGFβ2 ( p ≤ 0.05), TGFβ3 ( p ≤ 0.05), COL3A1 ( p ≤ 0.01), and P4HA2 ( p ≤ 0.001) downstream of IGF-II. Our results identify a novel IGF-II signaling axis and downstream targets that are regulated in a SOX9-dependent and -independent manner. Our findings provide novel insights on the role of IGF-II in promoting pulmonary fibrosis.

Introduction Education on health care for patients with diverse sexual orientation, sex characteristics and gender identities is lacking in Aotearoa's medical schools. Aim This study surveyed fifth-year medical students at the University of Otago Wellington (UOW) about confidence in providing health care to lesbian, gay, bisexual, transgender, queer, intersex and asexual (LGBTQIA+) patients to identify learning needs. Methods This anonymous cross-sectional survey was designed with input from an advisory group (community members, education, research and subject matter experts). It was administered on paper during class, using Likert scales (level of agreement) and open-ended questions. All fifth-year medical students at the UOW campus were invited to participate in May 2021. Data were analysed in Microsoft Excel (Microsoft Corporation) and free-text comments were analysed using template analysis. Results In total, 74.7% (71/95) of students completed a survey. Participants lacked knowledge and confidence in their consultation skills with LGBTQIA+ patients and did not feel they had enough teaching in this area. Most (≥78.8%) were comfortable with common terms, but half or fewer could explain intersex, gender affirmation and Takatāpui. Free-text comments revealed learning needs relating to consultation skills, ways to approach this topic with sensitivity, and a desire to learn more about the cultural context. Discussion Medical students view LGBTQIA+ health care as an important topic and want opportunities to improve knowledge and confidence in this area. Students lack confidence in consulting with LGBTQIA+ patients, suggesting that more education focused on practical experience and interactions with real patients would be of benefit.

Organ fibrosis, particularly of the lungs, causes significant morbidity and mortality. Effective treatments are needed to reduce the health burden. A fragment of the carboxyl-terminal end of collagen XVIII/endostatin reduces skin and lung fibrosis. This fragment was modified to facilitate its production in plants, which resulted in the recombinant fusion protein, END55. We found that expression of END55 had significant anti-fibrotic effects on the treatment and prevention of skin and lung fibrosis in a bleomycin mouse model. We validated these effects in a second mouse model of pulmonary fibrosis involving inducible, lung-targeted expression of transforming growth factor β1. END55 also exerted anti-fibrotic effects in human lung and skin tissues maintained in organ culture in which fibrosis was experimentally induced. The anti-fibrotic effect of END55 was mediated by a decrease in the expression of extracellular matrix genes and an increase in the levels of matrix-degrading enzymes. Finally, END55 reduced fibrosis in the lungs of patients with systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) who underwent lung transplantation due to the severity of their lung disease, displaying efficacy in human tissues directly relevant to human disease. These findings demonstrate that END55 is an effective anti-fibrotic therapy in different organs.

Young people are known to face challenges when accessing healthcare and generally have low rates of health service utilisation. Use of telehealth might be one way to improve access, but evidence is needed from young people as to how acceptable it is. This online survey of 15- to 25-year olds in the greater Wellington region of New Zealand sought young people's views on telehealth (phone and videocalls) as a means of accessing primary care. The survey included both forced-choice questions and free-text options. We report here on the free-text data from open-ended questions that were qualitatively analysed using template analysis. A total of 346 participants took part between August 6 and September 21, 2021, of whom 60% were female, 12% Māori (indigenous) ethnicity, and 38% had used telehealth methods of consulting previously. Analysis was undertaken of the free-text comments that were provided by 132 participants (38%). Although those contributing comments described both benefits and drawbacks to using telehealth, more drawbacks were cited, with specific examples given to illustrate a range of concerns and potential limitations of telehealth including privacy, communication difficulties and compromised quality of care. Participants thought telehealth could be used successfully in specific situations, for example by people concerned about leaving the house due to anxiety, illness or being immunocompromised and for simple consultations or when the person knows exactly what they need. Respondents expressed a strong desire to be offered the choice between in-person and telehealth consultations. Providing young people with a choice of consultation mode together with clear information about all aspects of a telehealth consultation is important if clinicians want young people to engage with this method of primary care service delivery., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Although cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010-2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014-2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample-size-adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P < .0001): (Stage IVA) nearly exclusive bone-only metastases (n = 59 049, 12.8%; median survival 12.7 months; common in lung, breast and prostate cancers); (IVB) predominant lung metastases (n = 62 491, 13.5%; 11.4 months; common in breast, stomach, kidney, ovary, uterus, thyroid, cervix and soft tissue cancers); (IVC) predominant liver/lung metastases (n = 130 014, 28.2%; 7.0 months; common in colorectum, pancreatic, lung, esophagus and stomach cancers); (IVD) bone/liver/lung metastases predominant over brain (n = 61 004, 13.2%; 5.9 months; common in lung and breast cancers); and (IVE) brain/lung metastases predominant over bone/liver (n = 148 799, 32.3%; 5.7 months; lung cancer and melanoma). Long-term survivors were identified, particularly in Stages IVA-B. A pan-cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provides 13% better prognostication than AJCC: 1-month concordance index of 0.67 (95% confidence interval [CI]: 0.66-0.67) vs 0.61 (95% CI: 0.60-0.61). STARS is simple, uses easily accessible variables, better prognosticates survival outcomes and provides a platform to develop novel metastasis-directed clinical trials., (© 2021 UICC.)

Background Young people need equitable access to high-quality sexual and reproductive health care to enjoy good sexual health. Methods This online survey of people aged 15-24years in a defined region of New Zealand asked about unmet need for sexual health care and sought views on improving access to sexual health care. Results Fivehundred participants took part in the study between August and October 2020, of whom 60% were female, 25% were of Māori (indigenous) ethnicity, and 21.4% were gender and/or sexuality diverse. Sixty percent had ever received sexual health care (300/500), and 74.3% received it from a general practice clinic (223/300). Overall, 41% (204/500) reported they needed, but had not received sexual health care in the past ('unmet need'). Reasons for unmet need included being shy, embarrassed or ashamed (74.5%, 152/204), fear of judgment by clinic staff (42.6%, 87/204), cost (32.8%, 67/204), concerns about confidentiality (28.9%, 59/204), and not knowing where to go (24%, 49/204). Māori participants were more likely to report not knowing where to go (32.1% vs 20%, P=0.04). Participants identified the need to reduce stigma, normalise sexual health care, improve convenience, affordability and awareness of services as key to improving access. Reassurance about confidentiality and being treated with kindness, empathy and respect were deemed critical to service acceptability. Conclusions Action is urgently needed at policy, funding and practice levels to improve access to services by: reducing societal stigma, normalising discussions around sexual health, improving affordability and raising awareness of services. Quality improvement is also needed in general practice to ensure young people can routinely access youth-friendly sexual and reproductive health care.

Background: New Zealand's response to the COVID-19 pandemic involved a nationwide stay-at-home lockdown in March-April 2020 that restricted access to primary healthcare services., Methods: An online survey of 15-24-year-olds in a high deprivation region of New Zealand asked about the need for, and receipt of, sexual healthcare during lockdown. Experience of telehealth and preferences for future receipt of sexual healthcare were also explored. Social media advertising was used to recruit participants over five weeks in August and October 2020., Results: The survey sample included 500 respondents comprising 58.8% females, 25.4% Māori (indigenous) ethnicity and 21.4% LGBTQI+ (lesbian, gay, bisexual, transgender, queer, intersex +) young people. During lockdown, 22.2% of respondents reported sexual health needs (111/500), but fewer than half this group got help (45%, 50/111), believing their issue could wait, or due to barriers contacting services and lack of information about service availability. Experience of telehealth consultations (by 28/50 participants) was mostly favourable though only 46% agreed it was easier than going to the clinic. Telehealth methods were the preferred option by some participants for future receipt of sexual healthcare; but for most scenarios suggested, respondents favoured in-person clinic visits., Conclusions: Young people experienced unmet need for sexual healthcare during lockdown in New Zealand, but not because services were unavailable. Findings point to the need for targeted information dissemination to young people about available services and the importance of seeking help during lockdown. More research is needed to understand the advantages and disadvantages of sexual healthcare delivered via telehealth to inform future service provision., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To understand young people's expectations of, and experience with sexual healthcare in New Zealand., Methods: Online survey of 15-24 year olds in a region with high socioeconomic deprivation, with selected outcomes compared for Māori and Europeans., Results: Of 500 respondents, 60% had received sexual healthcare (74.3% in general practice) and 81% were happy with care received. Fewer Māori and people not in education, employment, or training reported positive experiences of sexual healthcare on arrival and in the consultation., Conclusions: Findings highlight the need for equitable delivery of youth-friendly, culturally safe, sexual and reproductive healthcare in general practice settings., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2021 Taylor & Francis Group, LLC.)

INTRODUCTION Routinely following an evidence-based clinical pathway of care for bacterial sexually transmitted infections (STIs) such as chlamydia or gonorrhoea is important to help reduce the spread of infections, prevent reinfections and avoid associated health complications. AIM To develop an easy-to-use tool for routine use by primary care clinicians to ensure best practice management of patients tested for and diagnosed with chlamydia or gonorrhoea. METHODS The tool (a MedTech Advanced Form) was developed in consultation with seven primary care clinicians and included different tabs for use during the STI care pathway (testing, treatment, advice, partner notification and follow up) with clickable links to relevant online resources. The tool was trialled over 3 months by 19 clinicians in three Wellington primary care clinics - two youth health and a student health service. Outcome measures were frequency of use, completeness of fields related to best practice care and clinician acceptance of the tool (from focus group feedback). RESULTS The tool was used for approximately one in four patients who were tested during the trial period, with 'forgetting' reported as the most common reason for non-use. Clinician views about the tool were favourable, with most indicating they would like to continue use and would recommend it to colleagues. Documentation of best practice care was excellent; fields to record reasons for testing, discussion of sexual history, provision of treatment and advice given were used for most patients for whom the form was completed. CONCLUSIONS Inclusion of this STI management tool in the electronic patient records system appeared to improve primary care clinicians' delivery and documentation of best practice sexual health care at a practice level. Wider use of a modified version of this tool could facilitate more comprehensive best practice management of bacterial STIs.

Background: Reinfection with chlamydia or gonorrhea is common and can lead to significant reproductive health complications so testing for reinfection after treatment is recommended. This study described retesting and reinfection rates in regions of New Zealand with higher-than-average population rates of chlamydia., Methods: This retrospective cohort study analyzed chlamydia and gonorrhea testing data from 2 laboratories providing community testing services for 4 higher-rate regions in the North Island of New Zealand. Three years of data were obtained (2015-2017) to include a minimum of 6-month follow-up for all individuals. Retesting and reinfection rates between 6 weeks and 6 months of a positive result were calculated, and time to retesting was plotted using Kaplan-Meier curves. Logistic regression modeling was used to determine the odds of retesting (outcome 1) and reinfection (outcome 2) between 6 weeks and 6 months of follow-up., Results: Overall, 34% (3151/9241) of the cohort was retested within the recommended period, of whom 21% retested positive. Significant differences were observed in the odds of retesting by sex, age band, ethnic group, clinic type, and region (P < 0.01). The odds of a subsequent positive on retesting within 6 months differed significantly by sex, age band, and ethnic group (P < 0.01)., Conclusions: These findings reflect substantial gaps in the delivery of best-practice sexually transmitted infection management in New Zealand. There is a clear need to prioritize the implementation of clinic-level processes to support clinicians in the routine delivery of best-practice sexual health care. These should include routine provision of patient advice about retesting and strategies to promote timely and equitable access to retesting.

Type 2 insulin-like growth factor (IGF-II) levels are increased in fibrosing lung diseases such as idiopathic pulmonary fibrosis (IPF) and scleroderma/systemic sclerosis-associated pulmonary fibrosis (SSc). Our goal was to investigate the contribution of IGF receptors to IGF-II-mediated fibrosis in these diseases and identify other potential mechanisms key to the fibrotic process. Cognate receptor gene and protein expression were analyzed with qRT-PCR and immunoblot in primary fibroblasts derived from lung tissues of normal donors (NL) and patients with IPF or SSc. Compared to NL, steady-state receptor gene expression was decreased in SSc but not in IPF. IGF-II stimulation differentially decreased receptor mRNA and protein levels in NL, IPF, and SSc fibroblasts. Neutralizing antibody, siRNA, and receptor inhibition targeting endogenous IGF-II and its primary receptors, type 1 IGF receptor (IGF1R), IGF2R, and insulin receptor (IR) resulted in loss of the IGF-II response. IGF-II tipped the TIMP:MMP balance, promoting a fibrotic environment both intracellularly and extracellularly. Differentiation of fibroblasts into myofibroblasts by IGF-II was blocked with a TGFβ1 receptor inhibitor. IGF-II also increased TGFβ2 and TGFβ3 expression, with subsequent activation of canonical SMAD2/3 signaling. Therefore, IGF-II promoted fibrosis through IGF1R, IR, and IGF1R/IR, differentiated fibroblasts into myofibroblasts, decreased protease production and extracellular matrix degradation, and stimulated expression of two TGFβ isoforms, suggesting that IGF-II exerts pro-fibrotic effects via multiple mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Background: Evidence-based guidelines for the management of Chlamydia trachomatis and Neisseria gonorrhoeae recommend testing for reinfection 3-6 months following treatment, but retesting rates are typically low., Methods: Participants included six primary care clinics taking part in a pilot study of strategies designed to improve partner notification, follow-up and testing for reinfection. Rates of retesting between 6 weeks and 6 months of a positive chlamydia or gonorrhoea diagnosis were compared across two time periods: (1) a historical control period (no systematic approach to retesting) and (2) during an intervention period involving clinician education, patient advice about reinfection risk reduction and retesting, and short messaging service/text reminders sent 2-3 months post-treatment inviting return for retesting. Retesting was calculated for demographic subgroups (reported with 95% CI)., Results: Overall 25.4% (61 of 240, 95% CI 20.0 to 31.4) were retested during the control period and 47.9% (116 of 242, 95% CI 43.2 to 55.1) during the intervention period. Retesting rates increased across most demographic groups, with at least twofold increases observed for men, those aged 20-29 years old, and Māori and Pasifika ethnic groups. No significant difference was observed in repeat positivity rates for the two time periods, 18% (11 of 61) retested positive during the control and 16.4% (19 of 116) during the intervention period (p>0.05)., Conclusions: Clinician and patient information about retesting and a more systematic approach to follow-up resulted in significant increases in proportions tested for reinfection within 6 months. These simple strategies could readily be implemented into primary healthcare settings to address low rates of retesting for bacterial sexually transmitted infections., Trial Registration Number: ACTRN12616000837426., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to test the acceptability and utility of strategies designed to facilitate the delivery of clinical best practice for patients diagnosed with chlamydia or gonorrhea in primary care., Methods: A nonrandomized pilot intervention study with a historic control period was run over 9 months in six primary health care clinics (2 youth services, 3 low-fee clinics, and 1 student health service) in Wellington, New Zealand. "Study nurses" in participating clinics oversaw the implementation of strategies designed to facilitate partner notification and follow-up for patients diagnosed with chlamydia or gonorrhea. Clinics chose which of 2 approaches they wished to trial-either managing all study processes themselves or drawing on the assistance of an external specialist sexual health advisor. Outcome measures included acceptability and utility of study processes ascertained via structured interviews with study nurses and collection of clinical data., Results: Outcomes for 287 patients seen during the intervention were compared with 240 historic controls. Participant views on study processes were positive overall, and all clinics intended to continue all or most of the study processes implemented. During the intervention, substantial improvements were observed in documented patient management (sexual history, partner notification, and outcomes, P < 0.05). Increases were observed in percentages of patients reached for follow-up (74% vs. 26% at baseline, P < 0.05) and partners reported to have been notified (79% vs. 23%, P < 0.05)., Conclusions: Nurse-led strategies implemented were deemed acceptable and appeared to facilitate delivery of best practice care for patients diagnosed with bacterial sexually transmitted infections in participating primary care practices.

Th17 cells are a subset of effector T helper cells that produce interleukin (IL)-17A, IL-17F, IL-22, and IL-26, which can promote tissue inflammation and contribute to the pathogenesis of rheumatic, fibrosing, and other diseases. Research into these diseases is often limited by a lack of an animal model that closely mimics human disease and the paucity of patient clinical tissues. Therefore, the development of relevant experimental models is crucial. Three media formulations of Th17-skewing cocktail (CT) were evaluated for the ability to induce a Th17 signature in an ex vivo human skin model: CT9 contained αCD3, αCD28, IL-23, IL-1β, IFNγ, IL-4, IL-6, IL-21, and TGFβ; CT8 lacked IL-1β; and CT4 only contained αCD3, αCD28, IL-23, and IL-1β. Healthy donor skin was defatted, distributed as 3 mm punch biopsies, and incubated with one of the cocktail formulations or vehicle for 48 h. All of the cocktail formulations independently significantly stimulated the expression of each gene examined. CT4 induced IL-17A expression 1024-fold, significantly higher than CT9 and CT8. IL-17F was robustly stimulated by CT4 (1557-fold), CT9 (622-fold), and CT8 (111-fold), with significant differences between the CT groups. All of the formulations significantly induced IL-22 (16-42-fold). CT9 stimulated the highest IL-26 response (41-fold), which was significantly higher than CT4 and CT8. IL-10 was stimulated significantly higher with CT8 (10-fold) than CT4 or CT9. The secretion of IL-17A was significantly elevated with all cocktail formulations. Robust IL-17A / IL-17F cytokine induction was preferentially mediated by CT4, which suggested that its components are the minimal constituents necessary for the full induction of these genes in this human skin explant model, while the downstream cytokines were preferentially upregulated by CT4 ( IL-22 ), CT9 ( IL-26 ), or CT8 ( IL-10 ). In summary, our findings suggest that the induction of a Th17 phenotype in human skin is feasible and can be used as a model for rheumatic and fibrosing diseases where Th17 skewing is observed.

Insulin-like growth factor binding protein-5 (IGFBP-5) induces production of the extracellular matrix (ECM) components collagen and fibronectin both in vitro and in vivo and is overexpressed in patients with fibrosing lung diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). However, the mechanism by which IGFBP-5 exerts its fibrotic effect is incompletely understood. Recent reports have shown a substantial role of reactive oxygen species (ROS) in fibrosis; thus we hypothesized that IGFBP-5 induces production of ROS to mediate the profibrotic process. In vitro analyses revealed that ROS production was induced by recombinant and adenoviral vector-mediated IGFBP-5 (AdBP5) in a dose- and time-dependent manner, regulated through MEK/ERK and JNK signaling, and primarily mediated by NADPH oxidase (Nox). Silencing IGFBP-5 in SSc and IPF fibroblasts reduced ROS production. The antioxidants diphenyleneiodonium and N-acetylcysteine blocked IGFBP-5-stimulated ECM production in normal, SSc, and IPF human primary lung fibroblasts. In murine fibroblasts lacking critical components of the Nox machinery, AdBP5-stimulated ROS production and fibronectin expression were reduced compared with wild-type fibroblasts. IGFBP-5 stimulated transcriptional expression of Nox3 in human fibroblasts while selective knockdown of Nox3 reduced ROS production by IGFBP-5. Thus IGFBP-5 mediates fibrosis through production of ROS in a Nox-dependent manner.

Background: Connective tissue growth factor (CTGF), is a secreted matricellular factor that has been linked to increased risk of cardiovascular disease in diabetic subjects. Despite the biological role of CTGF in diabetes, it still remains unclear how CTGF expression is regulated. In this study, we aim to identify the clinical parameters that modulate plasma CTGF levels measured longitudinally in type 1 diabetic patients over a period of 10 years. A number of patients had negligible measured values of plasma CTGF that formed a point mass at zero, whereas others had high positive values of CTGF that were measured on a continuous scale. The observed combination of excessive zero and continuous positively distributed non-zero values in the CTGF outcome is referred to as semicontinuous data., Methods: We propose a novel application of a marginalized two-part model (mTP) extended to accommodate longitudinal semicontinuous data in which the marginal mean is expressed in terms of the covariates and estimates of their effect on the mean responses are generated. The continuous component is assumed to follow distributions that stem from the generalized gamma family whereas the binary measure is analyzed using logistic model and both have correlated random effects. Other approaches including the one- and two-part with uncorrelated and correlated random effects models were also applied and their estimates were all compared., Results: Our results using the mTP model identified intensive glucose control treatment and smoking as clinical factors that were associated with decreased and increased odds of observing non-zero CTGF values respectively. In addition, hemoglobin A1c, systolic blood pressure, and high density lipoprotein were all shown to be significant risk factors that contribute to increasing CTGF levels. These findings were consistently observed under the mTP model but varied with the distributions for the other models. Accuracy and precision of the mTP model was further validated using simulation studies., Conclusion: The mTP model identified new clinical determinants that modulate the levels of CTGF in diabetic subjects. Applicability of this approach can be extended to other biomarkers measured in patient populations that display a combination of negligible zero and non-zero values.

INTRODUCTION Bacterial sexually transmitted infections (STIs) contribute to a significant burden of ill-health despite being easy to diagnose and treat. STI management guidelines provide clinicians with evidence-based guidance on best-practice case management. AIM To determine the extent of adherence to STI management guidelines for partner notification, follow up and testing for reinfection following diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae. METHODS Retrospective review of electronic patient records for individuals diagnosed with chlamydia or gonorrhoea in eight primary care clinics in Wellington, New Zealand. At each clinic, 40 clinical records were reviewed (320 in total). Outcome measures were: overall numbers (%) of cases with documented evidence of reason for testing, sexual history, treatment, advice, partner notification and follow up. Partner notification outcomes were: n (%) with evidence of partner notification discussion and n (%) with partners advised, tested and treated. Proportions retested between 6 weeks and 6 months and n (%) positive on retesting were also determined. RESULTS Presenting features and treatment were generally well documented. Recent sexual history including number of partners was documented for half of cases reviewed (159/320). Partner notification discussion was documented for 74% (237/320) of cases, but only 24.4% (78/320) had documentation on numbers of partners notified and 17% (54/320) on numbers of partners treated. Testing for reinfection between 6 weeks and 6 months occurred for 24.7% (79/320), of whom 19% (15/79) re-tested positive. CONCLUSIONS This research suggests there are gaps in important aspects of patient care following bacterial STI diagnosis - a factor that may be perpetuating our high rates of infection. A more systematic approach will be needed to ensure people diagnosed with an STI receive the full cycle of care in line with best practice guidelines.

Objective: Connective tissue growth factor (CTGF), also known as CCN2, is a potent chemotactic and extracellular matrix-inducing matricellular protein that has been implicated in progression of inflammatory and fibroproliferative disorders. An emerging role of CTGF/CCN2 is that of a prosclerotic factor implicated in the development of cardiac disease. Our objective was to determine the role of CTGF/CCN2 as a predictor of cardiovascular events in type 2 diabetes in the Veterans Affairs Diabetes Trial (VADT) cohort., Research Design and Methods: Levels of CTGF/CCN2 were measured in 952 VADT patients a median of 1.9 years after entry into the study. Participants were followed for an average of 3.3 years for vascular outcomes. CTGF/CCN2 categories were defined as below the detectable limit (referent, 54.5%), lower half of detectable values (22.8%), and upper half of detectable values (22.7%). Hazard ratios (HRs) for cardiovascular end points in relation to CTGF/CCN2 categories were calculated by Cox proportional hazards models., Results: During follow-up, 4.8% had a myocardial infarction (MI), 6.9% had an MI or cardiovascular death, and 6.9% died. After adjustments by conventional risk factors, individuals in the highest category of CTGF/CCN2 were at higher risk of MI (HR 2.43 [95% CI 1.15, 5.14]), MI or cardiovascular death (HR 2.71 [95% CI 1.44, 5.08]), and all-cause mortality (HR 2.70 [95% CI 1.43, 5.08]) relative to individuals with CTGF below the detectable limit., Conclusions: Our study indicates that high levels of CTGF/CCN2 predict future MI and cardiovascular death in patients with type 2 diabetes., (© 2018 by the American Diabetes Association.)

Our laboratory recently made the novel observation that 5-hydroxytryptamine 1F (5-HT 1F ) receptor activation induces mitochondrial biogenesis (MB), the production of new, functional mitochondria, in vitro and in vivo. We sought to determine the mechanism linking the 5-HT 1F receptor to MB in renal proximal tubule cells. Using LY344864 , a selective 5-HT 1F receptor agonist, we determined that the 5-HT 1F receptor is coupled to Gα i/o and induces MB through Gβγ-dependent activation of Akt, endothelial nitric oxide synthase (eNOS), cyclic guanosine-monophosphate (cGMP), protein kinase G (PKG), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). We also report that the 5-HT 1F receptor signals through a second, Gβγ-dependent pathway that is linked by Akt phosphorylation of Raf. In contrast to the activated Akt pathway, Raf phosphorylation reduced extracellular signal regulated kinases (ERK1/2) and foxhead box O3a (FOXO3a) phosphorylation, suppressing an inhibitory MB pathway. These results demonstrate that the 5-HT 1F receptor regulates MB through Gβγ-dependent dual mechanisms that activate a stimulatory MB pathway, Akt/eNOS/cGMP/PKG/PGC-1α, while simultaneously repressing an inhibitory MB pathway, Raf/MEK/ERK/FOXO3a. Novel mechanisms of MB provide the foundation for new chemicals that induce MB to treat acute and chronic organ injuries.

Background: Long-acting reversible contraception (LARC) effectively protects against pregnancy but provides no protection against sexually transmitted infections (STIs)., Aim: To compare rates of chlamydia testing and diagnosis for women initiating long-acting versus oral contraception., Materials and Methods: Retrospective cohort study involving data collection for 6160 women initiating post-abortion contraception at a large New Zealand regional public hospital abortion clinic (2009-2012), with chlamydia testing data obtained from the local laboratory during two-year follow up. Negative binomial regression modelling examined the effect of contraceptive method on two outcome measures: chlamydia testing and chlamydia diagnosis (adjusting for potential covariates of age, ethnicity, past chlamydia infection, pregnancy history) in year one and two of follow up., Results: Two thousand seven hundred and twenty nine women (44%) received a LARC and 1764 (28.6%) were prescribed oral contraception. Adjusted testing rates differed by contraceptive method only in year one (P < 0.01): with higher rates among copper intrauterine device users (relative risk (RR) 1.2, 95% CI 1.06-1.35), and lower rates for implant users (RR 0.84, 95% CI 0.72-0.99) compared with oral contraceptive users (reference group). No significant differences were observed in chlamydia diagnosis rates by contraceptive method (P > 0.05). Younger age, past chlamydia infection, Maori and Pacific ethnicity were associated with higher rates of chlamydia diagnosis (P < 0.01)., Conclusions: Known STI-related risk factors (age, ethnicity, past infection) but not contraceptive method were independently related to rates of subsequent chlamydia diagnosis. This suggests that increased LARC uptake would not occur at the expense of chlamydia control. Regular screening and risk reduction advice (including condom use) are important chlamydia control measures for at-risk groups., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Testing for reinfection at 3 to 6 months following treatment for Chlamydia Trachomatis or Neisseria gonorrhoea is recommended in best practice sexual health management guidelines. This study aimed to describe rates of retesting and repeat positivity following diagnosis of chlamydia or gonorrhoea in a defined geographic region of New Zealand., Methods: Retrospective cohort study in Wellington, New Zealand involving analysis of laboratory data for chlamydia and gonorrhoea tests performed in primary care and sexual health clinics (July 2012-July 2015)., Outcome Measures: rate of retesting and rate of repeat positivity 6 weeks to 6 months after a positive result (index event). Kaplan-Meier curves were used to plot time from first index event to retest. Logistic regression modelling was used to determine the odds of retesting and repeat positivity between 6 weeks and 6 months of follow-up, adjusting for potential confounders (age, gender, ethnicity and socioeconomic deprivation)., Results: Overall 29.4% (1919/6530) of the cohort was retested between 6 weeks and 6 months, with 18% (347/1919) of those retested returning positive results. Lower odds of retesting were observed for males (OR 0.4, 95% CI 0.34-0.48), and individuals of NZ Maori (OR 0.72, 0.61-0.85) and Pacific ethnicities (OR 0.49, 0.39-0.62, reference European). Factors associated with higher odds of repeat positivity on retesting included male gender (OR 2.0, 1.14-2.82), age 15-19 years (OR 1.78, 1.32-2.41, reference 20-24 years), chlamydia/gonorrhoea co-infection (OR 2.39, 1.32-4.35, reference chlamydia only), Maori (OR 1.6, 1.18-2.17) and Pacific ethnicities (OR 1.88, 1.22-2.9, reference European)., Conclusions: We observed low adherence to STI retesting guidelines, and marked gender and ethnic disparities in rates of retesting and repeat positivity. Low retesting rates are suggestive of low levels of awareness of this aspect of patient management, and an absence of a systematic approach to retesting. High rates of repeat positivity reinforce the importance of advising patients about reducing their risk of reinfection, including notification and treatment of all recent sexual partners. Greater priority needs to be placed on increasing retesting and reducing rates of reinfection, with strategies implemented to improve these important aspects of patient care and population STI control.

INTRODUCTION Sexual health guidelines recommend that partner notification and testing for reinfection are undertaken when individuals are diagnosed with bacterial sexually transmitted infections (STIs). AIM To understand factors influencing the effective delivery of partner notification and follow up after diagnosis of STIs in primary care, and to identify strategies that might facilitate these processes. METHODS A postal survey was sent to 216 primary care doctors and nurses working in 72 Wellington primary care settings. Eligible clinicians were identified from laboratory testing data, and included clinicians who had diagnosed relatively high numbers of chlamydia and/or gonorrhoea cases during a 12-month period. Response frequencies were tabulated and chi-squared testing was used to test for significant differences between doctor and nurse responses for selected items. RESULTS In total, 121 surveys were completed (56% response rate) by 78 doctors and 43 nurses, from 55 primary care settings (76% of sites surveyed). Responding health professionals thought that patients were open to partner notification discussion, but appreciated that this sometimes raised difficult issues for patients. Lack of time or resources to follow up, and difficulty getting hold of patients, were cited as key factors that limit assessment of partner notification success. Factors deemed likely to facilitate partner notification included readily available patient resources, training to upskill practice team members, guidance on what to say and record, and access to external advice and assistance. DISCUSSION This study provides insight into provider- and patient-level factors perceived to be hindering successful partner notification. Strategies that could facilitate partner notification were identified, and suggestions made as to how these could be integrated into practice.

Fibroblasts are the effector cells of fibrosis characteristic of systemic sclerosis (SSc, scleroderma) and other fibrosing conditions. The excess production of extracellular matrix (ECM) proteins is the hallmark of fibrosis in different organs, such as skin and lung. Experiments designed to assess the pro-fibrotic capacity of factors, their signaling pathways, and potential inhibitors of their effects that are conducted in fibroblasts have paved the way for planning clinical trials in SSc. As such, fibroblasts have proven to be valuable tools in the search for effective anti-fibrotic therapies for fibrosis. Herein we highlight the characteristics of fibroblasts, their role in the etiology of fibrosis, utility in experimental assays, and contribution to drug development and clinical trials in SSc., Competing Interests: Disclosures: Conflict of interest: None of the authors has financial interest related to this study.

Objective: To determine whether there is regional variation in the immediate postabortion initiation of long-acting reversible contraception (LARC) in New Zealand., Materials and Methods: Retrospective analysis of nationally collected data on receipt of intrauterine and implantable contraception at the time of an abortion, together with demographic characteristics and region of residence for the year 2013., Results: Postabortion LARC initiation varied significantly between the 16 regions of New Zealand, ranging from 32% (95% CI 23.2-42) to 61.4% (95% CI 53.3-69). Implant use ranged from 6.8% to 32.7% across regions, and intrauterine method use ranged from 21.4% to 54.7%. Regional variation in total LARC uptake was most marked for under 20-year-olds (20.3% to 70.9%). The ratio of intrauterine to implant users ranged from 0.7 to 4.1 across regions, with intrauterine methods prescribed two and a half times more frequently nationwide., Conclusions: These regional differences in postabortion LARC initiation suggest there are between-clinic differences in prescribing. Reasons for these differences need to be examined to identify and address any barriers faced by clinics in the routine provision of postabortion LARC. Equitable access to LARC at the time of an abortion is needed throughout New Zealand to assist women in the prevention of future unintended pregnancies., (© 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Purpose: To describe changes in receipt of immediate postabortion long-acting reversible contraception (LARC) by adolescent and nulliparous women in New Zealand., Methods: Nationally collected data on immediate postabortion receipt of an intrauterine method (intrauterine device [IUD]/intrauterine system [IUS]) or contraceptive implant were analyzed to describe proportions and demographic characteristics of women receiving LARC between 2007 and 2013. Changes in uptake over time were presented for adolescent, nulliparous, and parous women., Results: Postabortion LARC uptake increased between 2007 and 2013, rising from 7.9% to 42.7% for adolescents and from 8.8% to 36.9% for nulliparous women. The increase was highest among nulliparous adolescents with a seven-fold increase in LARC uptake between 2007 and 2013. Adolescents had a five-fold increase and nulliparous women (of all ages) a four-fold increase. In 2013, IUD/IUS use was lowest among adolescents (22.4%) and increased with increasing age (43% by ages 40+ years), whereas implant use was highest among adolescents (20.3%) and decreased with increasing age (to 4.6% by age 40+ years). Nulliparous women had the lowest use of both IUD/IUS and implants in 2013, with 24.6% receiving an intrauterine method (compared with 43.2% for para 3+), and 12.3% an implant (compared with 17.5% for para 3+)., Conclusions: Despite an overall trend toward increased uptake of postabortion LARC by adolescent and nulliparous women, uptake in these groups still lags behind that of parous and older women. Reasons for differential uptake need to be explored and addressed if necessary to ensure all women have equitable access to the most effective methods of contraception., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Post-abortion initiation of long-acting reversible contraception (LARC) reduces subsequent abortion rates within 24 months, but the prevalence of post-abortion LARC use in New Zealand is unknown., Aim: To describe post-abortion initiation of intrauterine and implantable LARC methods in New Zealand between 2007 and 2012, and to determine what impact the introduction of government-funded (free) levonorgestrel (LNG) implants in August 2010 had on overall LARC use., Design and Setting: Retrospective observational study involving New Zealand abortion clinic data., Methods: Nationally collated data on post-abortion LARC insertions were obtained for the period 2007-2012, and individual-level discharge data for patients attending a large urban hospital abortion clinic were analysed using descriptive statistics to describe annual uptake rates, and the demographic profile of LARC users during this period. Logistic regression analyses examined whether LARC use differed by parity and/or age over time., Results: Post-abortion LARC use increased from 20.2% in 2007 to 45.6% in 2012. Intrauterine device use increased from 20.2% to 31.8% during this period, with implants contributing a further 14% to the overall use of LARC methods by 2012. Clinic data showed that LARC use increased among most demographic subgroups between 2009 and 2012, with the greatest increase among nulliparous under-20-year-olds (from 17.2% to 42.0%)., Conclusions: Post-abortion LARC use has been steadily increasing in New Zealand since 2007. Overall LARC use significantly increased following the introduction of government-funded implants, particularly among young and nulliparous women. Improving access to alternative methods of LARC may further increase uptake and reduce unwanted pregnancy rates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: The aims of this study were to compare immediate postabortion uptake of recently subsidized (no-cost) levonorgestrel-releasing implants with already available intrauterine and shorter-acting methods and to compare the incidence of subsequent pregnancies (ending in birth or abortion) within 2 years., Study Design: Retrospective chart review of 4698 women attending a New Zealand public hospital abortion clinic over 2 years (2010-2012) to describe postabortion contraceptive choice, with follow-up via clinic and national births records to assess subsequent pregnancies at 12, 24, 36, and 48 months., Results: Twenty percent of the cohort (934/4698) received an implant, 26% an intrauterine method (927 copper intrauterine device, 301 levonorgestrel-releasing intrauterine system [LNG-IUS]), and 54% chose other shorter-acting methods (2536/4698). Method choice was significantly associated with age, ethnicity, and pregnancy history (p < .001). At 24 months, the unadjusted incidence of subsequent abortion for implant users was 3.8% (95% confidence interval [CI] = 2.5-5.0) and 11.6% (95% CI = 10.3-12.8) for those choosing other short-acting methods. By 48 months, 6.6% of implant users had a subsequent abortion (compared with 18.3% for short-acting methods). The incidence of continued pregnancy at 24 months was 6.3% (95% CI = 4.4-8.1) for implant users and 15.7% (95% CI = 14-17.2) for those choosing other short-acting methods. Adjusted hazard ratios (HRs) for subsequent abortion were lowest for women initiating an implant (HR = 0.26, 95% CI = 0.20-0.35) or LNG-IUS (HR = 0.26, 0.16-0.44, reference group: short-acting methods)., Conclusions: Immediate postabortion insertion of an implant significantly reduced rates of subsequent pregnancy for at least 2 years. Abortion service providers should ensure women have barrier-free access to all long-acting reversible contraceptions to delay or prevent pregnancy., Implications: Initiation of an levonorgestrel implant immediately postabortion was associated with a 74% reduction in subsequent abortion over the next 4 years compared with use of short-acting methods. Implants were popular among adolescents-a group at high-risk of subsequent pregnancy, and who have not historically been considered appropriate candidates for intrauterine contraceptive methods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Angiotensin II (AngII) plays a critical role in the regulation of vascular tone and blood pressure mainly via regulation of Ca(2+) mobilization. Several reports have implicated sphingosine kinase 1 (SK1)/sphingosine 1-phosphate (S1P) in the mobilization of intracellular Ca(2+) through a yet-undefined mechanism. Here we demonstrate that AngII-induces biphasic calcium entry in vascular smooth muscle cells, consisting of an immediate peak due to inositol tris-phosphate-dependent release of intracellular calcium, followed by a sustained transmembrane Ca(2+) influx through store-operated calcium channels (SOCs). Inhibition of SK1 attenuates the second phase of transmembrane Ca(2+) influx, suggesting a role for SK1 in AngII-dependent activation of SOC. Intracellular S1P triggers SOC-dependent Ca(2+) influx independent of S1P receptors, whereas external application of S1P stimulated S1P receptor-dependent Ca(2+) influx that is insensitive to inhibitors of SOCs, suggesting that the SK1/S1P axis regulates store-operated calcium entry via intracellular rather than extracellular actions. Genetic deletion of SK1 significantly inhibits both the acute hypertensive response to AngII in anaesthetized SK1 knockout mice and the sustained hypertensive response to continuous infusion of AngII in conscious animals. Collectively these data implicate SK1 as the missing link that connects the angiotensin AT1A receptor to transmembrane Ca(2+) influx and identify SOCs as a potential intracellular target for SK1.

Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT1F) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]-4-fluorobenzamide; 1-100 nM) increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone-uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase β, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1β subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT1F receptor blocked agonist-induced MB. Furthermore, LY344864 increased peroxisome proliferator-activated receptor coactivator 1-α, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT1F receptor is linked to MB, 5-HT1F receptor agonism promotes MB in vitro and in vivo, and 5-HT1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction., (U.S. Government work not protected by U.S. copyright.)

Objectives: Experiments were conducted to evaluate whether or not bovine supramammary lymph node extract (LNE) could support cell proliferation when it was substituted for bovine growth serum (BGS) in cell culture media., Materials and Methods: Two different preparations of LNE were tested. The first yielded protein concentration of 3 mg/mL and the second contained 27 mg/mL protein. Three cell lines (MDA-MB-435, MAC-T and 1C6) were used in serum starvation assays to evaluate LNE. Cell proliferation assays were used to determine growth stimulation in the presence of LNE, and short-term or rapid adaptation cultures were evaluated for LNE effects on cell survival., Results: Heat-inactivated preparation 1 supported cell proliferation as well as or better (12-39%) than BGS following 2 days of serum starvation in culture. The second lymph node preparation provided a stimulatory effect (263-702% greater than BGS across all cell lines) following serum starvation at 2.7 and 5.4 mg/mL protein supplementation. A gradual adaptation process with lymph node supplementation into media maintained cell population growth on a short-term basis. However, once cells were trypsinized or scraped and re-seeded into 2.7 mg/mL LNE protein containing media, cells were unable to re-adhere, leaving them detached, and eventually appearing to be dead., Conclusions: Substitution of BGS with LNE protein dramatically stimulated cells to proliferate, but did not allow for rapid cell population growth adaptation in vitro.

A central aim of robotics research is to design robots that can perform in the real world; a real world that is often highly changeable in nature. An important challenge for researchers is therefore to produce robots that can improve their performance when the environment is stable, and adapt when the environment changes. This paper reports on experiments which show how evolutionary methods can provide lifelong adaptation for robots, and how this evolutionary process was embodied on the robot itself. A unique combination of training and lifelong adaptation are used, and this paper highlights the importance of training to this approach.

The field of Artificial Immune Systems (AIS) concerns the study and development of computationally interesting abstractions of the immune system. This survey tracks the development of AIS since its inception, and then attempts to make an assessment of its usefulness, defined in terms of 'distinctiveness' and 'effectiveness.' In this paper, the standard types of AIS are examined--Negative Selection, Clonal Selection and Immune Networks--as well as a new breed of AIS, based on the immunological 'danger theory.' The paper concludes that all types of AIS largely satisfy the criteria outlined for being useful, but only two types of AIS satisfy both criteria with any certainty.

Motivation: Perhaps the greatest challenge of modern biology is to develop accurate in silico models of cells. To do this we require computational formalisms for both simulation (how according to the model the state of the cell evolves over time) and identification (learning a model cell from observation of states). We propose the use of qualitative reasoning (QR) as a unified formalism for both tasks. The two most commonly used alternative methods of modelling biochemical pathways are ordinary differential equations (ODEs), and logical/graph-based (LG) models., Results: The QR formalism we use is an abstraction of ODEs. It enables the behaviour of many ODEs, with different functional forms and parameters, to be captured in a single QR model. QR has the advantage over LG models of explicitly including dynamics. To simulate biochemical pathways we have developed 'enzyme' and 'metabolite' QR building blocks that fit together to form models. These models are finite, directly executable, easy to interpret and robust. To identify QR models we have developed heuristic chemoinformatics graph analysis and machine learning procedures. The graph analysis procedure is a series of constraints and heuristics that limit the number of ways metabolites can combine to form pathways. The machine learning procedure is generate-and-test inductive logic programming. We illustrate the use of QR for modelling and simulation using the example of glycolysis., Availability: All data and programs used are available on request.

This study compared the growth indexes of first-grade, white children living in geographic areas of high poverty (n = 281) and low poverty (n = 442) in the state of Washington. Obesity was the most common growth deviance observed in these children. In the low-poverty area, 18% of children had a weight for height greater than the 90th percentile on the National Center for Health Statistics (NCHS) growth standards, whereas only 12% of children from the high-poverty area were in this category. Neither area had high numbers of children with reduced weight for height (less than the 10th percentile on the NCHS growth standards), but children from the high-poverty area were almost twice as likely to be short for their age; 9% of children from the high-poverty area and 5% of children from the low-poverty area had height-for-age values less than the 10th percentile on the NCHS growth standards. Criteria used to determine students' eligibility for financial support for school lunch did not accurately identify children who were thin or short. The prevalence of obesity in these first-grade children suggests that school-based growth screening as well as weight management and physical fitness programs are needed to identify and avert childhood obesity.