Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients' experiences, willingness, and preferences.

STUDY QUESTION: Are patients willing to discuss the possibility of treatment being unsuccessful as part of routine care offered at clinics, and what are the factors associated with this willingness? SUMMARY ANSWER: Nine in every 10 patients are willing to discuss this possibility as part of routine care, with willingness being associated with higher perceived benefits, lower barriers, and stronger positive attitudes towards it. WHAT IS KNOWN ALREADY: Fifty-eight percent of patients who complete up to three cycles of IVF/ICSI in the UK do not achieve a live birth. Offering psychosocial care for unsuccessful fertility treatment (PCUFT), defined as assistance and guidance on the implications of treatment being unsuccessful, could reduce the psychosocial distress patients experience when it happens, and promote positive adjustment to this loss. Research shows 56% of patients are willing to plan for an unsuccessful cycle, but little is known about their willingness and preferences towards discussing the possibility of definitive unsuccessful treatment. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a theoretically driven and patient-centred bilingual (English, Portuguese) mixed-methods online survey. The survey was disseminated via social media (April 2021-January 2022). Eligibility criteria included being aged 18 or older, waiting to or undergoing an IVF/ICSI cycle, or having completed a cycle within the previous 6 months without achieving a pregnancy. Out of 651 people accessing the survey, 451 (69.3%) consented to participate. From these, 100 did not complete 50% of the survey questions, nine did not report on the primary outcome variable (willingness), and 342 completed the survey (completion rate 75.8%, 338 women). PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey was informed by the Health Belief Model (HBM) and Theory of Planned Behaviour (TPB). Quantitative questions covered sociodemographic characteristics and treatment history. Quantitative and qualitative questions gathered data on past experiences, willingness, and preferences (with whom, what, how and when) to receive PCUFT, as well as theory-informed factors hypothesized to be associated with patients' willingness to receive it. Descriptive and inferential statistics were used on quantitative data about PCUFT experiences, willingness, and preferences, and thematic analysis was applied to textual data. Two logistic regressions were used to investigate the factors associated with patients' willingness. MAIN RESULTS AND THE ROLE OF CHANCE: Participants were, on average, 36 years old and most resided in Portugal (59.9%) and the UK (38.0%). The majority (97.1%) were in a relationship for around 10 years, and 86.3% were childless. Participants were undergoing treatment for, on average, 2 years [SD = 2.11, range: 0-12 years], with most (71.8%) having completed at least one IVF/ICSI cycle in the past, almost all (93.5%) without success. Around one-third (34.9%) reported having received PCUFT. Thematic analysis showed participants received it mainly from their consultant. The main topic discussed was patients' low prognosis, with the emphasis being put on achieving a positive outcome. Almost all participants (93.3%) would like to receive PCUFT. Reported preferences indicated that 78.6% wanted to receive it from a psychologist/psychiatrist/counsellor, mostly in case of a bad prognosis (79.4%), emotional distress (73.5%), or difficulties in accepting the possibility of treatment being unsuccessful (71.2%). The preferred time to receive PCUFT was before initiating the first cycle (73.3%), while the preferred format was in an individual (mean = 6.37, SD = 1.17; in 1-7 scale) or couple (mean = 6.34, SD = 1.24; in 1-7 scale) session. Thematic analysis showed participants would like PCUFT to provide an overview of treatment and all possible outcomes tailored to each patient's circumstances and to encompass psychosocial support, mainly focused on coping strategies to process loss and sustain hope towards the future. Willingness to receive PCUFT was associated with higher perceived benefit of building psychosocial resources and coping strategies (odds ratios (ORs) 3.40, 95% CI 1.23-9.38), lower perceived barrier of triggering negative emotions (OR 0.49, 95% CI 0.24-0.98), and stronger positive attitudes about PCUFT being beneficial and useful (OR 3.32, 95% CI 2.12-5.20). LIMITATIONS, REASONS FOR CAUTION: Self-selected sample, mainly composed of female patients who had not yet achieved their parenthood goals. The small number of participants unwilling to receive PCUFT reduced statistical power. The primary outcome variable was intentions, and research shows a moderate association between intentions and actual behaviour. WIDER IMPLICATIONS OF THE FINDINGS: Fertility clinics should provide patients with early opportunities to discuss the possibility of their treatment being unsuccessful as part of routine care. PCUFT should focus on minimizing suffering associated with grief and loss by reassuring patients they can cope with any treatment outcome, promoting coping resources, and signposting to additional support. STUDY FUNDING/COMPETING INTEREST(S): M.S.-L. holds a doctoral fellowship from the Portuguese Foundation for Science and Technology, I.P. [Fundação para a Ciência e a Tecnologia] (FCT; SFRH/BD/144429/2019). R.C. holds a post-doctoral fellowship supported by the European Social Fund (ESF) and FCT (SFRH/BPD/117597/2016). The EPIUnit, ITR and CIPsi (PSI/01662) are also financed by FCT through the Portuguese State Budget, in the scope of the projects UIDB/04750/2020, LA/P/0064/2020 and UIDB/PSI/01662/2020, respectively. Dr Gameiro reports consultancy fees from TMRW Life Sciences and Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International and Gedeon Richter, grants from Merck Serono Ltd, an affiliate of Merck KgaA, Darmstadt, Germany. TRIAL REGISTRATION NUMBER: N/A.

Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

Methanotrophic denitrification in wastewater treatment: microbial aspects and engineering strategies.

Anaerobic technologies are consolidated for sewage treatment and are the core processes for mining marketable products from waste streams. However, anaerobic effluents are supersaturated with methane, which represents a liability regarding greenhouse gas emissions. Meanwhile, anaerobic technologies are not capable of nitrogen removal, which is required to ensure environmental protection. Methane oxidation and denitrification processes can be combined to address both issues concurrently. Aerobic methane oxidizers can release intermediate organic compounds that can be used by conventional denitrifiers as electron donors. Alternatively, anoxic methanotrophic species combine methane oxidation with either nitrate or nitrite reduction in the same metabolism. Engineered systems need to overcome the long doubling times and low NOx consumption rates of anoxic methanotrophic microorganisms. Another commonly reported bottleneck of methanotrophic denitrification relates to gas-liquid mass transfer limitations. Although anaerobic effluents are supersaturated with methane, experimental setups usually rely on methane supply in a gaseous mode. Hence, possibilities for the application of methane-oxidation coupled to denitrification in full scale might be overlooked. Moreover, syntrophic relationships among methane oxidizers, denitrifiers, nitrifiers, and other microorganisms (such as anammox) are not well understood. Integrating mixed populations with various metabolic abilities could allow for more robust methane-driven wastewater denitrification systems. This review presents an overview of the metabolic capabilities of methane oxidation and denitrification and discusses technological aspects that allow for the application of methanotrophic denitrification at larger scales.

Clinical correlations and long-term follow-up in 100 patients with sarcoglycanopathies.

BACKGROUND AND PURPOSE: To describe a large series of patients with α, ß, and γ sarcoglycanopathies (LGMD-R3, R4, and R5) and study phenotypic correlations and disease progression. METHODS: A multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time-to-event analysis was performed. RESULTS: One hundred patients (54 γ-SG; 41 α-SG; 5 ß-SG) from 80 families were included. The γ-SG patients had earlier disease onset than α-SG patients (5.5 vs. 8 years; p = 0.022) and ß-SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow-up of 22.9 years, 65.3% of patients were wheelchair-bound (66.7% α-SG, 67.3% γ-SG, 40% ß-SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ-SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α-SG patients showed genetic heterogeneity, whereas >90% of γ-SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified. CONCLUSIONS: This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.

Genome-enabled prediction of reproductive traits in Nellore cattle using parametric models and machine learning methods.

This study aimed to assess the predictive ability of different machine learning (ML) methods for genomic prediction of reproductive traits in Nellore cattle. The studied traits were age at first calving (AFC), scrotal circumference (SC), early pregnancy (EP) and stayability (STAY). The numbers of genotyped animals and SNP markers available were 2342 and 321 419 (AFC), 4671 and 309 486 (SC), 2681 and 319 619 (STAY) and 3356 and 319 108 (EP). Predictive ability of support vector regression (SVR), Bayesian regularized artificial neural network (BRANN) and random forest (RF) were compared with results obtained using parametric models (genomic best linear unbiased predictor, GBLUP, and Bayesian least absolute shrinkage and selection operator, BLASSO). A 5-fold cross-validation strategy was performed and the average prediction accuracy (ACC) and mean squared errors (MSE) were computed. The ACC was defined as the linear correlation between predicted and observed breeding values for categorical traits (EP and STAY) and as the correlation between predicted and observed adjusted phenotypes divided by the square root of the estimated heritability for continuous traits (AFC and SC). The average ACC varied from low to moderate depending on the trait and model under consideration, ranging between 0.56 and 0.63 (AFC), 0.27 and 0.36 (SC), 0.57 and 0.67 (EP), and 0.52 and 0.62 (STAY). SVR provided slightly better accuracies than the parametric models for all traits, increasing the prediction accuracy for AFC to around 6.3 and 4.8% compared with GBLUP and BLASSO respectively. Likewise, there was an increase of 8.3% for SC, 4.5% for EP and 4.8% for STAY, comparing SVR with both GBLUP and BLASSO. In contrast, the RF and BRANN did not present competitive predictive ability compared with the parametric models. The results indicate that SVR is a suitable method for genome-enabled prediction of reproductive traits in Nellore cattle. Further, the optimal kernel bandwidth parameter in the SVR model was trait-dependent, thus, a fine-tuning for this hyper-parameter in the training phase is crucial.

Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients.

Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are robust and protective. Workshop participants explored whether NGRA for cosmetic ingredients can be protective of human health, and reviewed examples of NGRA for cosmetic ingredients. From the limited examples available, it is clear that NGRA is still in its infancy, and further case studies are needed to determine whether safety decisions are sufficiently protective and not overly conservative. Seven areas were identified to help progress application of NGRA, including further investments in case studies that elaborate on scenarios frequently encountered by industry and regulators, including those where a 'high risk' conclusion would be expected. These will provide confidence that the tools and approaches can reliably discern differing levels of risk. Furthermore, frameworks to guide performance and reporting should be developed.

Start-up of an aerobic granular sludge system from stored granules: Evaluating the impact of storage period on biomass activity and stability and the effect of temperature on nitrification and phosphorus removal rates.

Aerobic granular sludge (AGS) has been considered a breakthrough within the wastewater treatment sector. However, the long reactor start-up for the formation of granules is challenging and may hinder the spread of this technology. To circumvent this obstacle, inoculation of the reactors with pre-formed granules from existing plants is an interesting approach. In this context, issues related to biomass storage becomes very relevant. In this study, reactivation of aerobic granular biomass after storage was evaluated in a sequencing batch reactor (SBR) designed for achieving simultaneous organic matter, nitrogen and phosphorus removal. Two different scenarios, short (40 days) and long (180 days) storage periods, were assessed, and their influence on the granules physical properties and bioactivity was addressed. The results revealed that the granules stored for a shorter period showed higher resistance to breakage and underwent smooth color changes. On the other hand, the biomass stored for a longer period acquired a dark color and was more susceptible to disruption during reactivation. The granules stored for 6 months become swollen and exhibited an irregular morphology and fluffy structure within the first days of reactivation. Consequently, their settling properties were adversely affected, and some parameters such as the food-to-microorganism ratio had to be adjusted to prevent granules disintegration. Regarding the bioactivity of important microbial functional groups, COD removal was rapidly restored within a few days of SBR operation with the biomass stored for a shorter period. However, it took longer for the biomass stored for 180 days to reach the same performance observed for the granules stored for 40 days. A similar trend is valid for nitrification. In the experiments with sludge stored for a longer time, it took almost twice as long to reach effluent ammonium concentrations lower than 1 mg NH4+-N L-1 compared to the test using biomass stored for 40 days. Phosphate removal was strongly affected by biomass storage, especially after 180 days of inactivity, a condition found to be detrimental for polyphosphate-accumulating organisms. Finally, cycle tests were also conducted to assess substrate conversion rates for comparison between different trials and evaluate the influence of temperature (10-35 °C) on nitrification and phosphate removal rates.

What is the frequency of floor of the mouth lesions? A descritive study of 4,016 cases.

BACKGROUND: The aim of this study was to investigate the frequency of oral lesions in the floor of the mouth from representative oral pathology centres in Latin America. MATERIAL AND METHODS: This study was conducted on biopsies obtained from January of 1978 to December of 2018 at nine Latin America oral and maxillofacial pathology centres. Gender, age and histopathological diagnosis were evaluated. Data were analysed using descriptive methods. Chi-square test was used for pairwise comparisons. RESULTS: From 114,893 samples, 4,016 lesions (3.49%) occurred in the floor of the mouth. Brazil showed 3,777 cases (94%), Mexico 182 cases (4.5%) and Argentina 57 cases (1.4%). Benign lesions represented 65.1% (2,617 cases), followed by 34.9% (1,404 cases) of malignant disorders. Lesions of epithelial origin were more frequent (1,964 cases; 48.9%), followed by salivary glands (1,245 cases; 31%) and soft tissue lesions (475 cases; 11.7%). The most common histological subtypes were oral squamous cell carcinoma (1,347 cases; 33.5%), ranula (724 cases; 18%), oral leukoplakia (476 cases; 11.8%) and inflammatory fibrous hyperplasia (239 cases; 5.9%). The lesion affected males in 2,129 cases and females in 1,897 cases. CONCLUSIONS: In the current study, lesions in the floor of the mouth represented 3.49% of biopsies submitted to oral pathology services and oral squamous cell carcinoma, ranula and leukoplakia were the most common lesions.

Malignant transformation of oral leukoplakia: a multicentric retrospective study in Brazilian population.

BACKGROUND: Among the oral potentially malignant disorders, leukoplakia stands out as the most prevalent. The purpose of this study was to analyse the clinical-pathological features of oral leukoplakia in groups of patients from three major pathology centers in two different regions of Brazil, in order to determine which factors would be associated to the clinical risk of malignant transformation. MATERIAL AND METHODS: A total of 148 patients was analyzed, and data regarding gender, age, site, classification of the clinical subtype, harmful habits such as use of tobacco and alcohol, time of evolution and presence of dysplasia were collected. The association between risk factors and malignant transformation was investigated using the chi-square test and Fischer's exact test for correlation of variables. A significance level of 5% (p≤0.05) was used. RESULTS: The mean age of the patients was 60 years, and 56% were female. Most of the lesions (34,5%) were located in the lateral and ventral regions of the tongue. Of the 148 patients, ninety had clinical follow-up. Malignant transformation occurred in 13 patients (8.8%), with an average of 44 months of follow up. CONCLUSIONS: Non-smoker, nonhomogeneous clinical presentation, location at the tongue, and the presence of high degree of dysplasia were statistically relevant factors associated with a higher risk of transformation transformation.

An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Mortality risk among women exposed to violence in Brazil: a population-based exploratory analysis.

OBJECTIVES: The objective of this study was to estimate mortality risk among women exposed to violence in Brazil using population-based data. STUDY DESIGN: This study used a linked database containing nearly 800,000 violence (against women) notifications and 16,500 associated deaths over the period 2011-2016. METHODS: Aggregate age-standardized population-based rates of mortality were built to estimate risk ratios (RRs) at the national and state level, and for different forms of violence and causes of death, as well as type of offender involved, and across various characteristics of the women. RRs compared the rate of mortality among women exposed to violence with that in the general population of women - excess mortality due to violence was also derived from this comparison. The analysis was divided into two time periods (2011-13 and 2014-16). RESULTS: During 2014-16, women exposed to violence had an estimated mortality risk that was 8.3 [95% confidence interval (CI): 8.2-8.5] times higher than that of the general woman population, and an estimated 100 women died on a weekly basis as a direct or indirect consequence of exposure to violence. Higher (all-cause) mortality risk was associated with physical violence and violence that involved repetition and that was self-inflicted. The risk of mortality increased when the cause of death involved external causes (RR: 51.2, 95% CI: 49.6-52.8). When death was attributable to (i) non-communicable diseases and (ii) communicable, maternal, neonatal, and nutritional diseases, the risk was 5.4 [95% CI: 5.3-5.6] and 6.7 [95% CI: 6.1-7.2] times, respectively. Women at greatest (all-cause) mortality risk include white and multiracial (parda) and single women in the age group 10-29 years, who live in the northeast part of the country. When the offender was a partner/ex., women aged 10-19 years showed the greatest (all-cause) mortality risk at 16.9 [95% CI: 13.9-19.8] times. Higher risk was also observed within the age group 30-59 years when death was attributable to external causes (RR: 74.6, 95% CI: 71.3-77.9). For younger women and girls, there was a clear gradient in (all-cause) mortality risk, with those living in the poorest municipalities at greater risk. Age-specific mortality risk also showed significant variation within and across states. CONCLUSIONS: This analysis suggests that most women exposed to violence will likely experience an increased risk of mortality, regardless of her place of residence, age group, racial/ethnic background, marital status situation, and socio-economic status. The estimated RRs are only an approximation given the design of this analysis and should be interpreted with caution.

Filtering Statistics on Networks.

Compression, filtering, and cryptography, as well as the sampling of complex systems, can be seen as processing information. A large initial configuration or input space is nontrivially mapped to a smaller set of output or final states. We explored the statistics of filtering of simple patterns on a number of deterministic and random graphs as a tractable example of such information processing in complex systems. In this problem, multiple inputs map to the same output, and the statistics of filtering is represented by the distribution of this degeneracy. For a few simple filter patterns on a ring, we obtained an exact solution of the problem and numerically described more difficult filter setups. For each of the filter patterns and networks, we found three key numbers that essentially describe the statistics of filtering and compared them for different networks. Our results for networks with diverse architectures are essentially determined by two factors: whether the graphs structure is deterministic or random and the vertex degree. We find that filtering in random graphs produces much richer statistics than in deterministic graphs, reflecting the greater complexity of such graphs. Increasing the graph's degree reduces this statistical richness, while being at its maximum at the smallest degree not equal to two. A filter pattern with a strong dependence on the neighbourhood of a node is much more sensitive to these effects.

Factors associated with disordered eating behaviours in adolescents with Type 1 diabetes.

AIMS: To assess the occurrence of disordered eating behaviours in teenagers with Type 1 diabetes and to compare characteristics according to level of disordered eating behaviours. METHODS: In this cross-sectional study, we collected adolescents' demographic and diabetes management data by parent-youth interview and chart review. Teenagers completed psychosocial surveys, including the Diabetes Eating Problem Survey-Revised (DEPS-R), a diabetes-specific measure of disordered eating behaviours. We categorized teenagers according to level of disordered eating behaviours: low, DEPS-R score <10; moderate, DEPS-R score 10-19; and high, DEPS-R score ≥20. RESULTS: The 178 teenagers (48% girls) were aged 14.9±1.3 years, with diabetes duration of 7.4±3.7 years. Most (59%) had low, 26% had moderate, and 15% had high levels of disordered eating behaviours. Several biomedical and psychosocial characteristics differed by level of disordered eating behaviours. There were more girls in the moderate (62%) and high (65%) than in the low level of disordered eating behaviours group (37%; P=0.003) and more obese teenagers in the moderate (13%) and high (27%) groups than in the low group (4%; P=0.0003). Frequency of daily blood glucose monitoring decreased (P=0.0006) and HbA1c level increased (P=0.01) with greater level of disordered eating behaviours. A greater level of disordered eating behaviours was also associated with poorer treatment adherence, more negative affect regarding blood glucose monitoring, poorer quality of life, and more depressive symptoms (all P<0.0001), along with more diabetes-specific family conflict (P=0.01). CONCLUSIONS: Identifying teenagers with Type 1 diabetes who have moderate and high levels of disordered eating behaviours may prevent progression to eating disorders and substantial morbidity by directing support and intervention efforts to those in need.

Diagnostic usefulness of plexus magnetic resonance imaging in chronic inflammatory demyelinating polyradiculopathy without electrodiagnostic criteria of demyelination.

BACKGROUND AND PURPOSE: The usefulness of plexus magnetic resonance imaging (MRI) in the diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP) without definite European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria is currently unclear. METHODS: Data from consecutive patients with clinical manifestations suggesting CIDP, with or without (CIDP-D and CIDP-ND, respectively) definite EFNS/PNS electrodiagnostic criteria, and referred for plexus MRI in our imaging centre were retrospectively analysed. An expert committee of neurologists compared the level of suspicion of CIDP in CIDP-ND patients to the blinded/unblinded MRI findings. Plexus MRI was reviewed by a neuroradiologist blinded to the final diagnosis. RESULTS: In all, 38 patients were assessed with suspected CIDP-ND [7/38 (18%) probable; 13/38 (34%) possible; 18/38 (47%), no EFNS/PNS electrodiagnostic criteria], plus 10 with CIDP-D. Thirty-six of the 38 (95%) fulfilled clinical criteria of CIDP variants, including pure sensory neuropathy in 22/36 (61%). Plexus MRI showed abnormalities in 22/38 (58%) patients including increased nerve signal intensity on T2-weighted images in 22/22 (100%), nerve enlargement in 20/22 (91%) and contrast enhancement in 8/22 (36%). Plexus MRI enabled the expert committee's final diagnosis to be adjusted in 7/38 (18%) patients, and in conjunction with nerve conduction studies was a supportive criterion to classify 7/24 (29%) patients as definite CIDP. MRI abnormalities were more asymmetrical (P = 0.03) and less diffuse (P = 0.1) in CIDP-ND than in CIDP-D. CONCLUSIONS: Our observations suggest that plexus MRI makes a valuable contribution to the diagnosis of CIDP-ND patients. Further studies are needed to investigate inter-rater reliability of clinical and imaging criteria of CIDP in these patients, and the impact on outcomes.

Fermented whey dairy beverage offers protection against Salmonella enterica ssp. enterica serovar Typhimurium infection in mice.

Fermented whey dairy beverages are dairy products obtained by fermentation from a mixture of milk and whey. These beverages have important health benefits, which could be improved with the addition of probiotic cultures. This study assessed the protective effect of the cosupplementation of a probiotic culture (Lactobacillus casei 01) with a fermented whey dairy beverage against infection by Salmonella enterica ssp. enterica serovar Typhimurium in a murine model. Two fermented whey dairy beverages were prepared: conventional (FWB; starter culture) and probiotic (PFWB; starter and probiotic cultures). In the first set of experiments, Balb/C female mice were treated with FWB or PFWB, challenged with Salmonella Typhimurium, and analyzed for clinical signs, weight loss, and mortality for 20 d postinfection. In the second set of experiments, mice were treated with FWB or PFWB, challenged with Salmonella Typhimurium, and killed on d 10 postinfection. The liver, colon, and ileum were used for myeloperoxidase, eosinophil peroxidase, and histological analysis and translocation to the liver. The contents from the small intestine were used for secretory IgA determination. The FWB treatment showed a better effect on animal survival (70%), translocation of the pathogen to the liver (2 out of 10), histopathology (fewer lesions), and inflammation than PFWB, which presented 50% animal survival, translocation in 5 out of 10 animals, and higher lesions. The control group presented 40% animal survival, translocation in 6 out of 10 animals, and severe lesions. Therefore, FWB was deemed to have a greater protective effect against Salmonella Typhimurium infection in the murine model compared with PFWB.

The effects of a full-scale anaerobic side-stream reactor on sludge decay and biomass activity.

A full-scale anaerobic side-stream reactor (ASSR) for sludge reduction was monitored in terms of sludge production and compared with the previous conventional activated sludge configuration (CAS). A detailed solid mass balance was calculated on the whole full-scale plant to estimate the sludge reduction associated with the ASSR. The activity of the biomass, which undergoes alternation of aerobic and anaerobic conditions, was investigated by the respirometric test. The ASSR promoted a reduction of heterotrophic biomass activity and the substrate consumption rate in the activated sludge implemented with ASSR (AS + ASSR) was 36% smaller than in the CAS period. The solid mass balance indicated a sludge reduction of 28%. During the 270-day operation, the observed sludge yield passed from 0.438 kgTSS/kgCOD in the CAS to 0.315 in the AS + ASSR configuration. The solubilization of chemical oxygen demand (COD), NH4 +-N and orthophosphate were verified under anaerobic conditions. The results suggest that the possible mechanisms of sludge reduction were the increase of the system sludge retention time (SRT) by ASSR addition, and the reduction in heterotrophic biomass activity added to the organic compounds' hydrolysis.

Vertebrate SLRP family evolution and the subfunctionalization of osteoglycin gene duplicates in teleost fish.

BACKGROUND: Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment. RESULTS: The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro. CONCLUSIONS: Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.

Raman micro-spectroscopy analysis of different sperm regions: a species comparison.

STUDY QUESTION: Is Raman micro-spectroscopy a valid approach to assess the biochemical hallmarks of sperm regions (head, midpiece and tail) in four different species? SUMMARY ANSWER: Non-invasive Raman micro-spectroscopy provides spectral patterns enabling the biochemical characterization of the three sperm regions in the four species, revealing however high similarities for each region among species. WHAT IS KNOWN ALREADY: Raman micro-spectroscopy has been described as an innovative method to assess sperm features having the potential to be used as a non-invasive selection tool. However, except for nuclear DNA, the identification and assignment of spectral bands in Raman-profiles to the different sperm regions is scarce and controversial. STUDY DESIGN SIZE, DURATION: Raman spectra from head, midpiece and tail of four different species were obtained. Sperm samples were collected and smeared on microscope slides. Air dried samples were subjected to Raman analysis using previously standardized procedures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm samples from (i) two donors attending the infertility clinic at the Centre of Reproductive Medicine and Andrology; (ii) two C57BL/6 -TgN (ACTbEGFP) 1Osb adult mice; (iii) two adult Cynomolgus monkeys (Macaca fascicularis) and (iv) two sea urchins (Arbacia punctulata) were used to characterize and compare their spectral profiles. Differences and similarities were confirmed by principal component analysis (PCA). MAIN RESULTS AND THE ROLE OF CHANCE: Several novel region-specific peaks were identified. The three regions could be differentiated by distinctive Raman patterns irrespective of the species. However, regardless of the specie, their main spectral pattern remains mostly unchanged. These results were corroborated by the PCA analysis and suggest that the basic constituents of spermatozoa are biochemically similar among species. LIMITATIONS REASONS FOR CAUTION: Further research should be performed in live sperm to validate the detected spectral bands and their use as markers of distinctive regions. WIDER IMPLICATIONS OF THE FINDINGS: Raman peaks that have never been described in the sperm cell were detected. Particularly important are those that are unique to the midpiece as they might be a reference to the identification of sperm mitochondria, whose function is highly correlated with that of sperm. In the future, Raman micro-spectroscopy has the potential to be applied in assessment of male fertility. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by BMBF project 'Sperm Ident' (FKZ:13N13024) and the DAAD-CRUP bilateral exchange program (AI A06/16-57213087). S.A. is a recipient of a fellowship from the Portuguese foundation for science and technology (FCT-SFRH/BPD/110160/2015) and R.DC. is a recipient of a DAAD PhD stipend (91590556). There is no competing interest.

Finding the Optimal Nets for Self-Folding Kirigami.

Three-dimensional shells can be synthesized from the spontaneous self-folding of two-dimensional templates of interconnected panels, called nets. However, some nets are more likely to self-fold into the desired shell under random movements. The optimal nets are the ones that maximize the number of vertex connections, i.e., vertices that have only two of its faces cut away from each other in the net. Previous methods for finding such nets are based on random search, and thus, they do not guarantee the optimal solution. Here, we propose a deterministic procedure. We map the connectivity of the shell into a shell graph, where the nodes and links of the graph represent the vertices and edges of the shell, respectively. Identifying the nets that maximize the number of vertex connections corresponds to finding the set of maximum leaf spanning trees of the shell graph. This method allows us not only to design the self-assembly of much larger shell structures but also to apply additional design criteria, as a complete catalog of the maximum leaf spanning trees is obtained.