Pseudovirion-binding and neutralizing antibodies to cutaneous Human Papillomaviruses correlated to presence of HPV DNA in skin.

We compared seroreactivity to Human papillomavirus (HPV) antigens measured with two different high-throughput assays. One method used GST-L1 fusion proteins and the other heparin-bound HPV pseudovirions as antigens and both methods used multiplexed fluorescent beads for detection. For six HPV types (5, 6, 15, 16, 32 and 38), seroreactivity could be measured in parallel for 434 serum samples from non-immunosuppressed patients with skin lesions (squamous cell carcinoma of the skin, basal cell carcinoma of the skin, actinic keratosis and benign skin lesions). Biopsies from the skin lesions were tested for presence of HPV DNA using three different PCR methods, with typing by sequencing. Among the types included in the serological tests, HPV DNA of types HPV5, 15, 38 and 76 were most frequently detected in the tumours. Serum samples from subjects with HPV DNA positive biopsies and randomly selected serum samples from subjects with HPV DNA negative biopsies were also tested with neutralization assays with HPV5, 38 and 76 pseudovirions. Agreement of the three serological methods varied from poor to moderate and showed limited consistency. Type-specific seroprevalences among patients positive for the same type of HPV DNA (sensitivity of serology) was improved with the pseudovirion-based method (average of 40%, maximum 63%) compared to the GST-L1 method (average of 20%, maximum of 25%). Neutralization was the most sensitive assay for HPV38 (50%). In summary, the pseudovirion-based methods appeared to have an improved sensitivity

The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome : a systematic review and meta-analysis of randomized controlled trials

Objective: Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps remain regarding its efficacy and the specific outcomes in this population. This review evaluates the effectiveness of metformin and lifestyle modification compared with placebo in the management of PCOS and will inform the forthcoming, 2023 evidence-based PCOS guidelines. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, PsycINFO, All EBM, and CINAHL. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomized controlled trials published in English through July 2022. Results: Moderate certainty of evidence showed a larger reduction of body mass index (BMI) (mean difference [MD] −0.53, 95% confidence interval [CI] −0.95 to −0.12 kg/m2 ), homeostatic model assessment for insulin resistance (MD −0.50, 95% CI −0.91 to −0.09) (critical outcomes), and fasting glucose (MD −0.13, 95% CI −0.19 to −0.07 mmol/L) with metformin compared to placebo with increased mild gastrointestinal adverse effects (odds ratio [OR] 7.67, 95% CI 2.74–21.46). Low certainty of evidence showed a larger reduction of waist–hip ratio (MD −0.02, 95% CI −0.03 to −0.00), total cholesterol (MD −0.24, 95% CI −0.43 to −0.05 mmol/L), low density lipoprotein (MD −0.16, 95% CI −0.30 to −0.01 mmol/L), and triglycerides (MD −0.11, 95% CI −0.20 to −0.02 mmol/L) with metformin than placebo. Conclusions: Metformin should be considered an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance, and lipids

Phylogenetic position of an uncharacterized Brazilian strain of bovine papillomavirus in the genus Xipapillomavirus based on sequencing of the L1 open reading frame

The use of PCR assays with degenerate primers has suggested the existence of numerous as yet uncharacterized bovine papillomaviruses (BPV). Despite the endemic nature of BPV infections, the identification of BPV types in Brazilian cattle is still only sporadic. However, in a recent analysis of a partial segment of the L1 gene, we observed notable diversity among the BPV types detected. The aim of this study was to determine the phylogenetic position of the previously identified wild strain BPV/BR-UEL2 detected in the state of Paraná in Brazil. Since previous analysis of the partial L1 sequence had shown that this strain was most closely related to BPV type 4, genus-specific primers were designed. Phylogenetic analysis using complete L1 ORF sequences revealed that BPV/BR-UEL2 was related to BPV types classified in the genus Xipapillomavirus and shared the highest L1 nucleotide sequence similarity with BPV type 4 (78%). This finding suggests that BPV/BR-UEL2 should be classified as a potential new type of BPV in the genus Xipapillomavirus

Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome

STUDY QUESTION What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S) This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker’s fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker’s fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker’s fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker’s fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker’s fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC

Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Study question What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary answer International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. What is known already The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from 6 continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low- to low-quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus-based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, the evidence quality was low, and evidence-practice gaps persist. Study design, size, and duration The 2023 International Evidence-based Guideline update re-engaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength, and diversity and inclusion were considered throughout. Participants/materials, setting, and methods This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health, and other experts, alongside consumers, project management, evidence synthesis, statisticians, and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and 5 face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across 5 guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council. Main results and the role of chance The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care, and shared decision-making to improve patient experience, alongside greater research; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management. Limitations and reasons for caution Overall, recommendations are strengthened and evidence is improved but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. Wider implications of the findings The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input, and consumer preferences. Research recommendations have been generated, and a comprehensive multifaceted dissemination and translation programme supports the guideline with an integrated evaluation programme

ERP systems' capabilities for supply chain performance management

Purpose – The first purpose of this paper is to describe the demands from supply chain performance management (PM) on enterprise resource planning (ERP) systems. The second purpose is to evaluate the corresponding capabilities of common ERP systems. Design/methodology/approach – The first purpose is handled conceptually: by a literature review, a framework for the demand on ERP systems from supply chain PM is developed. The second purpose is handled with an empirical study, based on the framework. Respondents for 12 common ERP systems on the Swedish market are interviewed. Findings – A framework for the demand on ERP systems from supply chain PM is developed containing ten demands: a theoretical contribution. The studied ERP systems are found overall to have good supply chain PM capabilities, where the most supporting systems in this sense are Oracle and iScala. Research limitations/implications – The findings imply that future research on supply chain PM could focus less on ERP systems’ capabilities and more on how ERP systems are applied. Practical implications – The findings can give two types of input to companies purchasing or upgrading ERP systems; a “checklist” of demands from supply chain PM to consider and an evaluation of the corresponding capabilities for common ERP systems. Originality/value – Even though investments in ERP systems represent significant costs for companies, few studies in the area of ERP systems and supply chain PM are identified

Performance management in supply chains : logistics service providers' perspective

Purpose – Logistics service providers (LSPs) are important actors for creating logistics performance in supply chains. However, there is little previous research on how they handle the performance management process. The purpose of this paper is to explore the handling of the performance management process and its obstacles from the perspective of LSPs. Design/methodology/approach – A multiple-case study is conducted with the three largest LSPs in Sweden. Findings – The handling of the performance management process shows similarities among LSPs in selecting performance variables, defining metrics, and capturing real-time data. The differences are found in target setting, in report-making and analysing, and in the perceived demand for performance management. The following three perceived obstacles are found for supply chain performance management: lack of understanding and knowledge; poor capabilities for adapting performance metrics definitions; and lagging IT solutions for performance report-making. The findings indicate possibilities for an increased supply chain scope where activities are handled by the partner that has the best capabilities, improving efficiency in supply chains. Research limitations/implications – The study contributes to performance management theory by providing exploratory knowledge of the supply chain performance management process and its obstacles from the perspective of three LSPs. The study focuses on large LSPs and has respondents at the managerial level. Practical implications – The study reveals differing supply chain performance management practices among LSPs, which implies that customers can choose an LSP that handles performance management in the way required. Originality/value – Little previous research includes LSPs in studies of supply chain performance management. In particular it is unusual to have the perspective of LSPs and apply case-based methodology

Grazing and the geographical range of seaweeds : The introduced Fucus evanescens and the newly described Fucus radicans

Along the coast of temperate oceans brown algae of the genus Fucus form dense stands on rocky shores and are keystone species of the coastal ecosystem. These large seaweeds are perennial and function as substrate for many sessile marine organisms, provide shelter for fauna and juvenile fish, and are food source. A number of abiotic (e.g. wave-exposure, salinity and substrate) and biotic (e.g. herbivory and competition) factors structures these communities and determines the abundance and composition of fucoids at each specific site. Earlier studies have shown that herbivores may reduce growth of fucoids, thus affecting their distribution, and at high densities eliminate the species from previously occupied sites. In my thesis I focused on investigating herbivore-seaweed interactions and whether such interactions could influence the geographical range limits of Fucus species. A set of laboratory bioassays and a field survey were conducted (1) to investigate the resistance to grazing by a generalist gastropod between introduced (to Sweden) and native (Iceland) Fucus evanescens (Paper I),  (2) to study the distribution pattern of F. radicans and F. vesiculosus along the Swedish coast and specifically the southern limit of F. radicans, (3) to examine the abundance of herbivores in these two species, and (4) to test the hypothesis that Idotea baltica may contribute to restrict F. radicans to the Bothnian Sea (objective 2-4; Paper II). Fucus evanescens, a species that was introduced to the Swedish coast about 100 years ago, was found to be more resistant to grazing by L. littorea compared to F. evanescens from the native Icelandic populations.  It was also shown to contain a higher amount of phlorotannins; a putative chemical defence to herbivory. This indicates that development of resistance to herbivory could be important for a successful introduction and survival in a new range. No gradual change in the proportion, measured as % cover of either F. radicans or F. vesiculosus was found inside the range of F. radicans and its southernmost limit was abrupt without any corresponding abrupt change in any abiotic factor, e.g. salinity. Herbivores, i.e. Idotea spp., Gammarus spp. and Theodoxus fluviatils were found to be more abundant in F. radicans than in F. vesiculosus thalli indicating a habitat preference for F. radicans.  Further, Idotea baltica, whose range only overlaps with that of F. radicans in the south, was shown to prefer F. radicans over F. vesiculosus, possibly due to its lower content of phlorotannins. Based on these findings I propose that Idotea species may contribute in restricting the southern range of F. radicans, although further experiments, especially regarding competition with the larger F. vesiculosus need to be performed. In conclusion, biotic interactions e.g. the ability of to resist herbivore grazing by e.g. high phlorotannin content or having a structure less attractive as habitat to herbivores may be of importance in determining the geographic range of fucoids.Längs kusterna i de tempererade haven bildar brunalger av släktet Fucus täta bestånd på klippiga stränder och är ofta nyckelarter i kustekosystemen. Dessa tångarter är fleråriga och utgör substrat för många fastsittande organismer, ger skydd åt små rörliga djur och fiskyngel, samt utgör föda för betare så som gastropoder, amphipoder och isopoder. Faktorer som vågexponering, bottentyp, salthalt, näringshalter, bete och konkurrens strukturerar tångsamhällen och avgör hur vanlig varje tångart är på en viss lokal. I min avhandling har jag fokuserat på interaktionen mellan betare och tång, samt hur viktig denna interaktion är för att avgöra den geografiska utbredningen av tångarter. Tidigare studier har visat att betare kan minska tillväxten hos tång och på så sätt påverka dess utbredning. I höga densiteter kan de beta ner hela bestånd av tång så att den försvinner från lokaler där de tidigare vuxit. Resistens mot bete hos Fucus evanescens, ishavstång, som är introducerad till Skagerrak, Kattegat och sydvästra Östersjön och inhemsk i norra Atlanten och norra Stilla Havet undersöktes i betesförsök (Artikel I). En betare, generalisten Littorina littorea, strandsnäcka, som är inhemsk i Sverige, dit F. evanescens har introducerats, föredrog att äta F. evanescens från Island där den är inhemsk, framför F. evanescens från Sverige. Det här skulle kunna tyda på att ett välutvecklat försvar är viktigt för att alger som blir introducerade till nya områden ska kunna etablera sig i det nya området. Jag undersökte även utbredningen av den nyligen beskrivna tångarten Fucus radicans, smaltång (Artikel II). Resistensen mot betare hos F. radicans jämfördes med resistensen mot bete hos F. vesiculosus, blåstång, som växer tillsammans med F. radicans, genom att undersöka preferensen mellan de två arterna hos Idotea baltica, tånggråsugga (Artikel II). Det fanns ingen gradient i förekomsten av F. radicans eller F. vesiculosus inom F. radicans utbredningsområde. Istället observerades en ganska abrupt gräns för utbredningen av F. radicans i söder. Eftersom I. baltica, vars utbredning överlappar F. radicans utbredning i söder, föredrog att äta F. radicans framför F. vesiculosus, skulle F. radicans utbredning kunna påverkas av I. baltica. Både I. baltica och två andra betare, Gammarus spp. och Theodoxus fluviatilis, var vanligare i F. radicans än i F. vesiculosus i plantor insamlade i fält. Det innebär att de vanligaste betarna, även i fält, föredrar att uppehålla sig i F. radicans och antagligen konsumerar mer av F. radicans. Slutsatsen från de båda studierna är att betare och tångens försvar mot bete har potentialen att påverka utbredning av olika tångarter