Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the ...potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES.
Graphical abstract
Hiccups (singultus) usually present as a common annoyance lasting for short periods. Rarely, they may be the harbinger of a serious disease. We present the case of a 19-year-old man in which ...intractable hiccups was the first and most prominent symptom of a serious underlying neurologic disorder. The patient had been examined by his pediatrician, and despite multiple medical regiments and physical maneuvers, his symptoms persisted. A thorough head and neck examination revealed a right-sided vocal cord paralysis. This finding prompted obtaining a magnetic resonance imaging scan, which demonstrated a type I Arnold-Chiari malformation associated with a large cervicothoracic syringomyelia. The patient was referred to the neurosurgical service and subsequently underwent a ventriculoperitoneal shunt placement. There was considerable initial improvement in his neurologic status and cessation of the hiccups. However, the symptoms recurred within 1 month. The case report as well as a brief review of the relevant pathophysiologic and etiologic considerations and several treatment modalities for hiccups is presented.
This article is written jointly by the Director of Social Services and the Joint Commissioning Manager from the London Borough of Greenwich. It represents their personal views on the development of ...primary care groups, setting out the local picture, highlighting specific issues from the social service perspective and looking at the challenges and opportunities which lie ahead.The Government's proposals for modernising the National Health Service, and in particular its proposals for the development of primary care groups, are broadly welcome. However, they do raise a number of issues not only for social services departments, but also for local authorities in general. This article is a personal perspective on what these developments might mean for social services and the challenges and opportunities which are likely to arise.
Methods. The diagnostic performance of transrectal ultrasound (TRUS) gland volume and prostate specific antigen (PSA) results were evaluated in 204 men consecutively scheduled to undergo ...transurethral prostatic resection (TUR).
Results. Nonpalpable prostate cancer was detected by TRUS alone in 18% (29 of 161) and by TUR alone in 9% (14/161), for an overall cancer incidence of 27%. A predicted PSA value (TRUS gland volume × 0.20 ng/ml/g = polyclonal PSA) was used for comparison with serum PSA for each patient. TRUS positive predictive value improved from 52% to 86% when serum PSA exceeded the predicted value. The specificity and positive predictive value of PSA at 2.5 ng/ml were 23% and 37%, respectively, which increased to 88% and 72%, respectively, when serum PSA exceeded the predicted value.
Conclusions. Predicted PSA values produce decision levels near the 95th percentile for each patient and assist individual biopsy decisions better than grouped gland volume ranges. Wider application of TRUS and PSA in any clinical setting or early detection program is now possible.
Summary
The composition of the gut microbiota and excessive ingestion of high‐fat diets (HFD) are considered to be important factors for development of obesity. In this review we describe a coherent ...mechanism of action for the development of obesity, which involves the composition of gut microbiota, HFD, low‐grade inflammation, expression of fat translocase and scavenger receptor CD36, and the scavenger receptor class B type 1 (SR‐BI). SR‐BI binds to both lipids and lipopolysaccharide (LPS) from Gram‐negative bacteria, which may promote incorporation of LPS in chylomicrons (CMs). These CMs are transported via lymph to the circulation, where LPS is transferred to other lipoproteins by translocases, preferentially to HDL. LPS increases the SR‐BI binding, transcytosis of lipoproteins over the endothelial barrier,and endocytosis in adipocytes. Especially large size adipocytes with high metabolic activity absorb LPS‐rich lipoproteins. In addition, macrophages in adipose tissue internalize LPS‐lipoproteins. This may contribute to the polarization from M2 to M1 phenotype, which is a consequence of increased LPS delivery into the tissue during hypertrophy. In conclusion, evidence suggests that LPS is involved in the development of obesity as a direct targeting molecule for lipid delivery and storage in adipose tissue.
STUDY QUESTION
What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)?
...SUMMARY ANSWER
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively.
WHAT IS KNOWN ALREADY?
The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS.
STUDY DESIGN, SIZE, DURATION
From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20–40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark.
PARTICIPANTS/MATERIAL, SETTING, METHODS
We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2–5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured.
MAIN RESULTS AND THE ROLE OF CHANCE
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women < 30 years to 14.7% in women aged 30–34 years, and 10.2% in women ≥ 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for polycystic ovaries with a significant age-related decrease from 69.0% in women < 30 years to 55.8% in women aged 30–34 years, and 42.8% in women ≥ 35 years (P < 0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of polycystic ovaries in women with PCOS according to the Rotterdam criteria area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990–0.999 and AUC 0.992 (95% CI: 0.987–0.998), respectively, and an AMH cut-off value of 18 pmol/l and AMH Z-score of −0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total, AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of AFC > 19 or AMH > 35 in the age groups < 30, 30–34 and ≥ 35 years was 31.0 and 35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30–34 and ≥ 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6 and 4.8%, respectively.
LIMITATIONS, REASON FOR CAUTION
The participants of the study were all health-care workers, which may be a source of selection bias. Furthermore, the exclusion of hormonal contraceptive users from the study population may have biased the results, potentially excluding women with symptoms of PCOS.
WIDER IMPLICATIONS OF THE FINDINGS
AMH may be used as a marker of polycystic ovaries in PCOS. However, future studies are needed to validate AMH threshold levels, and AMH Z-score may be appropriate to adjust for the age-related decline in the AFC.
STUDY FUNDING/COMPETING INTEREST(S)
None.
TRIAL REGISTRATION NUMBER
Not applicable.
Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible ...explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated.
PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including <100 children. The main outcome measure was preterm birth (PTB defined as delivery <37 weeks of gestation), and a random effects model was used for meta-analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW, small for gestational age and perinatal mortality.
The search returned 1255 articles and 65 of these met the inclusion criteria. The following were identified as predictors for PTB in singletons: SC in couples with time to pregnancy (TTP) > 1 year versus SC singletons in couples with TTP ≤ 1 year adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB.
Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.
Building a quantum computer is a daunting challenge since it requires good control but also good isolation from the environment to minimize decoherence. It is therefore important to realize quantum ...gates efficiently, using as few operations as possible, to reduce the amount of required control and operation time and thus improve the quantum state coherence. Here we propose a superconducting circuit for implementing a tunable system consisting of a qutrit coupled to two qubits. This system can efficiently accomplish various quantum information tasks, including generation of entanglement of the two qubits and conditional three-qubit quantum gates, such as the Toffoli and Fredkin gates. Furthermore, the system realizes a conditional geometric gate which may be used for holonomic (non-adiabatic) quantum computing. The efficiency, robustness and universality of the presented circuit makes it a promising candidate to serve as a building block for larger networks capable of performing involved quantum computational tasks.
Biologics targeting interleukin (IL)‐17 and IL‐23 are generally well‐tolerated and considered safe, though adverse events are seen more often compared with placebo. The objectives of this systematic ...review and meta‐analysis were to assess the prevalence of adverse events in patients with psoriasis or psoriatic arthritis with any adverse events after 12, 16, 24 and 52 weeks of treatment with IL‐17 or IL‐23 inhibitors. Two independent authors searched the databases PubMed and EMBASE for studies reporting on adverse events in phase 3 trials of IL‐17 and IL‐23 inhibitors for patients with psoriasis and psoriatic arthritis. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Data synthesis was performed using a random‐effects model. In total, 44 publications (43 studies) were included in the analyses. The proportion of patients with any adverse events for all treatments pooled were 0.57 95% confidence interval (CI): 0.55–0.59 after 12 weeks, 0.52 (95% CI: 0.49–0.55) after 16 weeks, 0.72 (95% CI: 0.66–0.78) after 24 weeks and 0.81 (95% CI: 0.76–0.86) after 52 weeks. Across therapies, the most prevalent AEs were infections, nasopharyngitis and headache. For ixekizumab one of the most prevalent AEs was injection site reactions, reported in 15.7% of the patients after 52 weeks. Overall, IL‐17 and IL‐23 inhibitors appear to be well‐tolerated with good safety profiles. Our findings may aid the clinical decision making when choosing the most appropriate therapy for patients with moderate‐to‐severe psoriasis.