HES-SO Genève

Growing out of a child’s cognitive developmental history, formal operations become established at Cognitive development about the age of 12–15 years. Reflected in his ability to reason Adolescence hypothetically and independently on concrete states of affairs, these structures may be represented by reference to Logic combinatorial systems and to 4-groups. The essence of the Environmental differences logic of cultured adults and the basis for elementary scientific Individual differences thought are thereby provided. The rate at which a child progresses through the developmental succession may vary, especially from one culture to another. Different children also vary in terms of the areas of functioning to which they apply formal operations, according to their aptitudes and their professional specializations. Thus, although formal operations are logically independent of the reality content to which they are applied, it is best to test the young person in a field which is relevant to his career and interests.

The Clinical System In Parent-Infant Psychotherapy * An Overview of the Clinical Situation * The Parents Representational World * The Parents Representations Enacted * The Parent-Infant Interaction * The Nature and Formation of the Infants Representations * The Infants Representations Viewed Clinically * The Therapist Therapeutic Approaches In Parent-Infant Psychotherapy And Their Common * Approaches That Aim to Change the Parents Representation * Approaches That Aim to Change the Interactive Behaviors * Commonalities Among the Different Approaches Synthesis * The Motherhood Constellation * Some Wider Implications for Other Clinical Situations

BACKGROUND: There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. METHODS: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. RESULTS: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as 'strong' and plenary voting revealed 'strong agreement' for 99 (98%) recommendations. CONCLUSIONS: The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Abstract An integrative explanation proposes that culture and gender interact to produce fundamentally different patterns of association between positive and negative emotions. People in independent-based cultures (e.g. the United States) experience emotions in oppositional (i.e. bipolar) ways, whereas people in interdependent-based cultures (e.g. China) experience emotions in dialectic ways. These patterns are stronger for women than men in both cultures. In support of the theory, Study 1 showed that positive and negative emotions are strongly correlated inversely for American women and weakly correlated inversely for American men, but strongly correlated positively for Chinese women and weakly correlated positively for Chinese men. In Study 2, findings for Koreans, although mixed, were closer to the results for Chinese.

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single-cell transcriptomics, ribosome profiling, and two MS/MS search tools in combination. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides, including an immunogenic peptide derived from an open reading frame downstream of the melanoma stem cell marker gene ABCB5. These findings hold great promise for the discovery of previously unknown tumor antigens for cancer immunotherapy.

Introduction It is well documented that the prevalence of venous leg ulcers (VLUs) is increasing, coinciding with an ageing population. Accurate global prevalence of VLUs is difficult to estimate due to the range of methodologies used in studies and accuracy of reporting. (1) Venous ulceration is the most common type of leg ulceration and a significant clinical problem, affecting approximately 1% of the population and 3% of people over 80 years of age (2) in westernised countries. Moreover, the global prevalence of VLUs is predicted to escalate dramatically, as people are living longer, often with multiple comorbidities. Recent figures on the prevalence of VLUs are based on a small number of studies, conducted in Western countries, and the evidence is weak. However, it is estimated that 93% of VLUs will heal in 12 months, and 7% remain unhealed after five years. (3) Furthermore, the recurrence rate within 3 months after wound closure is as high as 70%. (4) (-6) Thus, cost-effective adjunct evidence-based treatment strategies and services are needed to help prevent these ulcers, facilitate healing when they occur and prevent recurrence. The impact of a VLU represents social, personal, financial and psychological costs on the individual and further economic drain on the health-care system. This brings the challenge of providing a standardised leg ulcer service which delivers evidence-based treatment for the patient and their ulcer. It is recognised there are variations in practice and barriers preventing the implementation of best practice. There are patients not receiving appropriate and timely treatment in the initial development of VLUs, effective management of their VLU and preventing recurrence once the VLU has healed. Health-care professionals (HCPs) and organisations must have confidence in the development process of clinical practice guidelines and have ownership of these guidelines to ensure those of the highest quality guide their practice. These systematic judgments can assist in policy development, and decision making, improve communication, reduce errors and improve patient outcomes. There is an abundance of studies and guidelines that are available and regularly updated, however, there is still variation in the quality of the services offered to patients with a VLU. There are also variations in the evidence and some recommendations contradict each other, which can cause confusion and be a barrier to implementation. (7) The difference in health-care organisational structures, management support and the responsibility of VLU management can vary in different countries, often causing confusion and a barrier to seeking treatment. These factors further complicate the guideline implementation process, which is generally known to be a challenge with many diseases. (8).

Abstract. The relationships between the distribution of alpine species and selected environmental variables are investigated by using two types of generalized linear models (GLMs) in a limited study area in the Valais region (Switzerland). The empirical relationships are used in a predictive sense to mimic the potential abundances of alpine species over a regular grid. Here, we present the results for the alpine sedge Carex curvula ssp. curvula . The modelling approach consists of (1) a binomial GLM, including only the mean annual temperature as explanatory variable, which is adjusted to species presence/absence data in the entire study area; (2) a logistic model restricted to stands occurring within the a priori defined temperature range for the species ‐ which allows ordinal abundance data to be adjusted; (3) the two species‐response functions combined in a GIS to generate a map of the species' potential abundance in the study area; (4) model predictions filtered by the classes of the qualitative variables under which the species never occur. Such a stratified approach used to better fit the variability within the optimal altitudinal zone for the species. Removing stand descriptions from altitudes too high or too low, where the species is unlikely to occur, enhances the global modelling performance by allowing the identification of important environmental variables only retained in the second model. The model evaluation is finally carried out with the γ‐measure of association in an ordinal contingency table. It shows that abundance is satisfactorily predicted for C. curvula .

Radiological changes and differences between cemented and uncemented components of Grammont reverse shoulder arthroplasties (DePuy) were analysed at a mean follow-up of 9.6 years (8 to 12). Of 122 reverse shoulder arthroplasties implanted in five shoulder centres between 1993 and 2000, a total of 68 (65 patients) were available for study. The indications for reversed shoulder arthroplasty were cuff tear arthropathy in 48 shoulders, revision of shoulder prostheses of various types in 11 and massive cuff tear in nine. The development of scapular notching, bony scapular spur formation, heterotopic ossification, glenoid and humeral radiolucencies, stem subsidence, radiological signs of stress shielding and resorption of the tuberosities were assessed on standardised true anteroposterior and axillary radiographs. A scapular notch was observed in 60 shoulders (88%) and was associated with the superolateral approach (p = 0.009). Glenoid radiolucency was present in 11 (16%), bony scapular spur and/or ossifications in 51 (75%), and subsidence of the stem and humeral radiolucency in more than three zones were present in three (8.8%) and in four (11.8%) of 34 cemented components, respectively, and in one (2.9%) and two (5.9%) of 34 uncemented components, respectively. Radiological signs of stress shielding were significantly more frequent with uncemented components (p < 0.001), as was resorption of the greater (p < 0.001) and lesser tuberosities (p = 0.009).

We report the detection of a planetary system with three Super-Earths orbiting HD 40307. HD 40307 is a K2 V metal-deficient star at a distance of only 13 parsec, which is part of the HARPS GTO high-precision planet-search programme. The three planets on circular orbits have very low minimum masses of 4.2, 6.9, and 9.2 Earth masses and periods of 4.3, 9.6, and 20.5 days, respectively. The planet with the shortest period is the lowest mass planet detected to-date orbiting a main sequence star. The detection of the correspondingly low amplitudes of the induced radial-velocity variations is secured completely by the 135 high-quality HARPS observations illustrated by the radial-velocity residuals around the 3-Keplerian solution of only 0.85 ms-1. Activity and bisector indicators exclude any significant perturbations of stellar intrinsic origin, which supports a planetary interpretation. In contrast to most planet-host stars, HD 40307 has a significantly sub-solar metallicity ([Fe/H] = -0.31), which suggests that very light planets might have a different dependence on host star metallicity than gas giant planets. In addition to the 3 planets close to the central star, a small drift in the radial-velocity residuals implies the presence of another companion in the system, the nature of which is still unknown.

Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecules, cells, and tissues across diverse states. This Perspective provides a vision on their design and how collaborative efforts to build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, and guiding experimental studies, offering new opportunities for understanding cellular functions and fostering interdisciplinary collaborations in open science.

This chapter argues for a radical departure from the classic paradigms of emotion psychology. It emphasizes the emotion process, that is, the dynamic time course of constantly changing affective tuning of organisms as based on continuous evaluative monitoring of their environment. Whereas many emotion psychologists have theoretically endorsed the notion of emotion as a process, most research has been firmly wedded to the notion of emotional state and its assessment via verbal labels. This situation has led to a theoretical and empirical impasse that only a paradigm shift can remedy. The component process model of emotion (Scherer, 1981, 1984, 1986, 1987) is used to illustrate the type of theoretical approach that, by providing an open architecture for process modeling, might be more germane to the dynamic nature of emotion processes. Most importantly, it is suggested that researchers go beyond classic linear process models and evaluate the potential of recently developed nonlinear dynamic modeling notions vis-à-vis the emotion phenomenon. Particular emphasis is given to the notions of coupled oscillators, as used in dynamic systems theory, and of hysteresis, a central concept in catastrophe theory.

The introduction of lipophilic derivatives of the naturally occurring heme precursor 5-aminolevulinic acid (5-ALA) into photomedicine has led to a true revival of this research area. 5-ALA-mediated photodynamic therapy (PDT) and fluorescence photodetection (FD) of neoplastic disease is probably one of the most selective cancer treatments currently known in oncology. To date, this method has been assessed experimentally for the treatment of various medical indications. However, the limited local bioavailability of 5-ALA has widely prevented its use in daily clinical practice. Although researchers were already aware of this drawback early during the development of 5-ALA-mediated PDT, only recently have well-established concepts in pharmaceutical science been adapted to investigate ways to overcome this drawback. Recently, two derivatives of 5-ALA, methylaminolevulinate (MAL) and hexylaminolevulinate (HAL), gained marketing authorization from the regulatory offices in Europe and Australia. MAL is marketed under the trade name Metvix for the treatment of actinic keratosis and difficult-to-treat basal cell carcinoma. HAL has recently been launched under the trade name Hexvix to improve the detection of superficial bladder cancer in Europe. This review will first present the fundamental concepts underlying the use of 5-ALA derivatives in PDT and FD from a chemical, biochemical and pharmaceutical point of view. Experimental evidences from preclinical data on the improvements and limits observed with 5-ALA derivatives will then be introduced. The state-of-the-art from clinical studies with 5-ALA esters will be discussed, with special emphasis placed on the process that led to the development of MAL in dermatology and to HAL in urology. Finally, we will discuss promising medical fields in which use of 5-ALA derivatives might potentially lead to further use of this methodology in photomedicine.

The neXtProt knowledgebase (https://www.nextprot.org) is an integrative resource providing both data on human protein and the tools to explore these. In order to provide comprehensive and up-to-date data, we evaluate and add new data sets. We describe the incorporation of three new data sets that provide expression, function, protein-protein binary interaction, post-translational modifications (PTM) and variant information. New SPARQL query examples illustrating uses of the new data were added. neXtProt has continued to develop tools for proteomics. We have improved the peptide uniqueness checker and have implemented a new protein digestion tool. Together, these tools make it possible to determine which proteases can be used to identify trypsin-resistant proteins by mass spectrometry. In terms of usability, we have finished revamping our web interface and completely rewritten our API. Our SPARQL endpoint now supports federated queries. All the neXtProt data are available via our user interface, API, SPARQL endpoint and FTP site, including the new PEFF 1.0 format files. Finally, the data on our FTP site is now CC BY 4.0 to promote its reuse.

Aims.We analyse the effects of a first generation of fast rotating massive stars on the dynamical and chemical properties of globular clusters.

Estrogens and progesterones are major drivers of breast development but also promote carcinogenesis in this organ. Yet, their respective roles and the mechanisms underlying their action in the human breast are unclear. Receptor activator of nuclear factor κB ligand (RANKL) has been identified as a pivotal paracrine mediator of progesterone function in mouse mammary gland development and mammary carcinogenesis. Whether the factor has the same role in humans is of clinical interest because an inhibitor for RANKL, denosumab, is already used for the treatment of bone disease and might benefit breast cancer patients. We show that progesterone receptor (PR) signaling failed to induce RANKL in PR(+) breast cancer cell lines and in dissociated, cultured breast epithelial cells. In clinical specimens from healthy donors and intact breast tissue microstructures, hormone response was maintained and RANKL expression was under progesterone control, which increased RNA stability. RANKL was sufficient to trigger cell proliferation and was required for progesterone-induced proliferation. The findings were validated in vivo where RANKL protein expression in the breast epithelium correlated with serum progesterone levels and the protein was expressed in a subset of luminal cells that express PR. Thus, important hormonal control mechanisms are conserved across species, making RANKL a potential target in breast cancer treatment and prevention.

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.

We identify the effective field theory describing the physics of super-Hubble scales and show it to be a special case of a class of effective field theories appropriate to open systems. Open systems are those that allow information to be exchanged between the degrees of freedom of interest and those that are integrated out, such as would be appropriate for particles moving through a fluid. Strictly speaking they cannot in general be described by an effective lagrangian; rather the appropriate ‘low-energy’ limit is instead a Lindblad equation describing the time-evolution of the density matrix of the slow degrees of freedom. We derive the equation relevant to super-Hubble modes of quantum fields in de Sitter (and near-de Sitter) spacetimes and derive two of its implications. We show that the evolution of the diagonal density-matrix elements quickly approach the Fokker-Planck equation of Starobinsky’s stochastic inflationary picture. This allows us both to identify the leading corrections and provide an alternative first-principles derivation of this picture’s stochastic noise and drift. (As applications we show that the noise for massless fields is independent of the details of the window function used, and also compute how the noise changes for systems with a sub-luminal speed of sound, c s < 1.) We then argue that the presence of interactions drive the off-diagonal density-matrix elements to zero in the field

OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.