Estudo longitudinal de famílias / Longitudinal study of families / Estudio longitudinal de familias

Introdução: O desenvolvimento da família é influenciado por diversos fatores de sua organização interna e de ordem ambiental, social, cultural, econômica e política. Em contexto de pobreza os riscos são maiores. Fatores de proteção, como boa organização familiar e rede social de apoio podem diminuir as consequências negativas da pobreza. São escassas as pesquisas longitudinais sobre vulnerabilidade e resiliência nas famílias. Objetivo: Este artigo descreve o desenvolvimento de três famílias ao longo de 15 anos, estudadas por meio de entrevistas em casa, parte de uma coorte populacional de um bairro de Porto Alegre (RS). Buscaram-se associações entre a qualidade das relações nessas famílias e sua saúde física e mental, especialmente a do filho, foco da pesquisa. Métodos: Selecionaram-se no arquivo da pesquisa as três primeiras famílias (do total de 148) das quais se tinham os resultados completos das cinco visitas realizadas aos quatro meses e aos dois, quatro, nove e 15 anos de um filho. Realizou-se análise qualitativa dos registros em busca de categorias para compreender a vida e as relações interpessoais nas famílias. O estudo foi realizado em conjunto por duas pesquisadoras, médicas especialistas em desenvolvimento humano. As categorias identificadas na análise e estudadas nas cinco etapas foram: configuração familiar, situação socioeconômica, situações traumáticas, saúde física, saúde relacional e mental, evolução cognitiva e escolar do filho. Resultados: As três famílias, todas de classe C, com filhos sem problemas de saúde física, tiveram evolução suficientemente boa, apesar de todas enfrentarem múltiplos problemas, inclusive separações e mortes precoces. A relação com o sistema de saúde e escola era boa e similar para as três. A jovem com menos problemas de saúde mental foi aquela que sofreu perdas mais importantes: morte dos pais. Tinha uma estrutura familiar multigeracional sólida desde a primeira infância, com relações interpessoais predominantemente colaborativas e amorosas. Conclusões: O artigo busca avançar na compreensão da resiliência nas famílias em situações de vulnerabilidade. Concluímos que essas três famílias, uma delas mais que as outras, foram suficientemente saudáveis na tarefa de educar seus filhos sem desenvolverem problemas mentais graves. Propomos que o bom desenvolvimento se associa com a adequação e amorosidade dos cuidados com a etapa do ciclo vital, mesmo enfrentando situações problemáticas. Essas qualidades precisam estar associadas à estabilidade socioeconômica básica e a bons serviços de saúde e escola.

Introduction: Family development is influenced by it's internal organization and environmental factors, socioeconomic, cultural and political. In poor contexts there are more risks to development. Protection factors like good family organization and social network may decrease the risks. Longitudinal research about vulnerability and resilience in families is scarse. Objective: This article describes the development of three families over 15 years through interviews at home. The families were part of a populational cohort of a neighborhood in Porto Alegre (RS). We looked for links between the quality of relationships and the physical and mental health of these families, especially of the child focus of the research. Methods: We selected in the research archives the first three families (of a total of 148) for which we had full results of the five interviews at four months and two, four, nine and fifteen years of a child. We did a qualitative analysis of the records looking for parameters to understand the life and interpersonal relationships of these families. This study was done by two researchers, both experts in Human Development. The categories identified in the analysis of the five phases were: family structure, socioeconomic situation, traumatic experiences, physical, mental and relational health and cognitive evolution of the child. Results: All three families belonged to economical class C. The children were in good physical health and had sufficiently good general development, having faced multiple problems, including parental separation and early parental death. The relationship with the health and school systems was good in all of them. The youth with less mental health problems was the one who suffered the heaviest loss: early death of both parents. Her family had strong multigenerational ties since her early days, with predominant collaborative and loving relationships. Conclusions: This article aims to contribute to the comprehension of resilience in families in the context of vulnerability. We can say that these three families were healthy enough in the task of bringing up children without any serious mental health problem. We suggest that healthy development is associated with loving interfamily relationships adequate to each phase of development, notwithstanding dramatic events. This needs to be supported by basic economic stability and adequate school and health systems.

Introducción: El desarrollo de la familia es influenciado por su organización interna y factores ambientales, sociales, culturales, económicos y políticos. En contextos pobres los riesgos son mayores. Factores de protección como buena organización familiar y red social de apoyo pueden disminuir las consecuencias negativas de la pobreza. Son pocas las investigaciones longitudinales de vulnerabilidad y resiliencia de las familias. Objetivo: Este artículo describe el estudio del desarrollo de tres familias a lo largo de 15 años, a través de entrevistas en domicilio, parte de una cohorte poblacional de un barrio de Porto Alegre (RS). Se buscaron correlaciones entre la calidad de las relaciones de esas familias y su salud física y mental, especialmente la del hijo foco de la investigación. Métodos: Fueron seleccionadas en el archivo de la investigación las tres primeras familias (de un total de 148) de las cuales se tenían los resultados completos de las cinco visitas realizadas, a los 4 meses, y a los 2, 4, 9, y 15 años de un hijo. Fue realizado un análisis cualitativo de los registros en busca de categorías para comprender la vida y las relaciones interpersonales en las familias. El estudio fue hecho en conjunto por dos investigadoras, médicas especialistas en desarrollo humano. Las categorías identificadas en el análisis y estudiadas en las cinco etapas fueron: configuración familiar, situación socioeconómica, situaciones traumáticas, salud física, salud relacional y mental, evolución cognitiva y escolar del hijo. Resultados: Las tres familias, todas de clase C, con hijos sin problemas de salud física, tuvieron evolución suficientemente buena, a pesar de que todas enfrentaron múltiples problemas, incluso separaciones y muertes precoces. La relación con el sistema de salud y escuela era buena y similar para las tres. La joven con menos problemas de salud mental fue aquella que sufrió las mayores pérdidas: muerte de los padres. Tenía una estructura familiar multigeneracional sólida desde la primera infancia, con relaciones interpersonales predominantemente colaborativas y amorosas. Conclusiones: El artículo pretende avanzar en la comprensión de la resiliencia en las familias en situaciones de vulnerabilidad. Concluimos que esas tres familias, una de ellas más que las otras, fueron suficientemente saludables en la tarea de educar a sus hijos sin que desarrollaran problemas mentales graves. Proponemos que el buen desarrollo se asocia con el amor y adecuación de los cuidados a la etapa del ciclo vital, aun enfrentando situaciones problemáticas. Esas calidades necesitan estar asociadas a la estabilidad socioeconómica básica y buenos servicios de salud y escuela.

Comparing motor development in children with hydrocephalus after treatment with ventriculoperitoneal shunt and endoscopic third ventriculostomy: a cross-sectional study.

Introduction: Ventriculoperitoneal shunt insertion (VPSI) and endoscopic third ventriculostomy (ETV) are the major procedures for treating pediatric hydrocephalus. However, studies comparing motor development following the two treatments are limited. Objective: We aimed to determine motor development outcomes in children with hydrocephalus up to 2 years of age after undergoing VPSI or ETV, to identify which surgical approach yields better motor outcomes and may be more effective for Malawian children. Methods: This was a cross-sectional study where we recruited two groups of participants: one group consisted of children with hydrocephalus treated with VP shunt whilst the other group were treated with ETV, at least 6 months prior to this study. Participants were identified from the hospital records and were called to come for neurodevelopmental assessment using the Malawi Development Assessment Tool (MDAT). Results: A total 152 children treated for hydrocephalus within an 18-month period met the inclusion criteria. Upon follow up and tracing, we recruited 25 children who had been treated: 12 had VPSI and 13 had ETV. MDAT revealed delays in both assessed motor domains: 19 out of the 25 children had delayed gross motor whilst 16 of 25 had delayed fine motor development. There was no significant difference between the shunted and the ETV groups. Conclusion: Children with hydrocephalus demonstrate delays in motor development six to 18 months after treatment with either VPSI or ETV. This may necessitate early and prolonged intensive rehabilitation to restore motor function after surgery. Long-term follow-up studies with bigger sample sizes are required to detect the effect of the two treatment approaches.

Not EF skills but play with real toys prevents screen time tantrums in children.

Limiting children's screen time has become a new parenting challenge. Due to the high attractiveness of media and digital devices, many children experience painful transitions in screen time to other activities. Screen time tantrums is a new concept that describes children's negative affect screen time limits. Knowing the factors that increase children's negative reactions will be helpful in parents and educators practice to prevent screen time tantrums or enrich children's nondigital activities, making them attractive alternatives to the media. Based on theoretical insights into the coping mechanisms of frustration and anger in preschool children, this study was aimed to explore the effects of executive functions skills, family activities, and children's play behavior with real toys on screen time tantrums. Sample included 654 caregiver-child pairs (M children age = 70.3 months, SD = 4.02). Results confirmed the hypothesis that play behavior with real toys is a stronger preventor of screen time tantrum than EF skills. The findings suggest that supporting play activity in preschool children might help them to avoid strong negative affects due to screen time limitation. The results of this study may be also considered as a support for the theoretical assumptions that play can be considered as a universal way of coping with frustration and anger in childhood.

A Novel NR5A1 Mutation in a Thai Boy with 46, XY DSD.

Disorders of sex development (DSD) can be classified as 46,XX DSD, 46,XY DSD, and sex chromosome DSD. Several underlying causes including associated genes have been reported. Steroidogenic factor-1 is encoded by the NR5A1 gene, a crucial regulator of steroidogenesis in the growth of the adrenal and gonadal tissues. It has been discovered to be responsible for 10 to 20% of 46, XY DSD cases. Here, we described a 2-month-old infant who had ambiguous genitalia and 46, XY. Using whole exome sequencing followed by polymerase chain reaction-Sanger sequencing, a novel heterozygous nonsense c.1249C > T (p.Gln417Ter) variant in the NR5A1 gene was identified. It is present in his mother but absent in his father and maternal aunt and uncle. At the age of 7 months, the patient received a monthly intramuscular injection of low-dose testosterone for 3 months in a row. His penile length and diameter increased from 1.8 to 3 cm and from 0.8 to 1.3 cm, respectively. The patient also had normal adrenal reserve function by adrenocorticotropic hormone stimulation test. This study identified a novel causative p.Q417X (c.1249C > T) variant in NR5A1 causing 46,XY DSD in a Thai boy which is inherited from his unaffected mother.

Unleashing the potential of cell painting assays for compound activities and hazards prediction.

The cell painting (CP) assay has emerged as a potent imaging-based high-throughput phenotypic profiling (HTPP) tool that provides comprehensive input data for in silico prediction of compound activities and potential hazards in drug discovery and toxicology. CP enables the rapid, multiplexed investigation of various molecular mechanisms for thousands of compounds at the single-cell level. The resulting large volumes of image data provide great opportunities but also pose challenges to image and data analysis routines as well as property prediction models. This review addresses the integration of CP-based phenotypic data together with or in substitute of structural information from compounds into machine (ML) and deep learning (DL) models to predict compound activities for various human-relevant disease endpoints and to identify the underlying modes-of-action (MoA) while avoiding unnecessary animal testing. The successful application of CP in combination with powerful ML/DL models promises further advances in understanding compound responses of cells guiding therapeutic development and risk assessment. Therefore, this review highlights the importance of unlocking the potential of CP assays when combined with molecular fingerprints for compound evaluation and discusses the current challenges that are associated with this approach.

Agroforestry in Madagascar: past, present, and future.

Agroforestry systems promise a high multifunctionality providing cash and subsistence yields as well as other ecosystem services. Such land systems may be particularly promising for smallholders in tropical landscapes due to high labour intensity and productivity on limited land. Focusing on Madagascar, we here describe the history of agroforestry in the country and review the current literature on agroforestry outcomes as well as factors promoting and hindering agroforest establishment and maintenance. From this, we discuss the potential future of agroforestry in Madagascar. Historically, many crops farmed today in agroforestry systems were originally introduced as plantation crops, mostly in the nineteenth century. Since then, people co-opted these crops into mixed agroforestry systems, often focusing on clove, vanilla, coffee, or cocoa in combination with fruit trees or, for clove, with livestock. Other crops are also integrated, but shares are comparatively low. Overall, 27.4% of Malagasy exports are crops typically farmed in agroforestry systems, providing income for at least 500,000 farmers. Outcomes of agroforestry for biodiversity and ecosystem services are commonly researched, showing benefits over annual crops and monocultures. Social-economic outcomes, including yields, are more scarcely researched, but findings point towards financial benefits for smallholder farmers and a sense of community and collective memory. However, findings emphasize that research gaps remain in terms of geographic and crop coverage, also for ecological outcomes. Looking to the future, we highlight the need to overcome hurdles such as land tenure insecurity, financial barriers to implementation, and unstable value chains to scale agroforestry in Madagascar to the benefit of multifunctional land systems and human wellbeing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10457-024-00975-y.

Anthropogenic, environmental and temporal associations with vertebrate road mortality in a wildland-urban interface of a biodiverse desert ecoregion.

Road mortality adversely affects wildlife populations. As urbanization and infrastructure densities expand, transportation and wildlife management aim to mitigate wildlife-vehicle conflicts while conserving biodiversity. Roadways in aridland ecosystems can invariably and adversely impact wildlife differently from temperate and other biomes, yet these rapidly urbanizing regions are understudied as are urban-rural gradients. We conducted road-cruise surveys (n = 204; 2018-2023) to assess anthropogenic, environmental, and temporal factors associated with vertebrate roadkill across the wildland-urban interface of Arizona's biodiverse Sonoran Desert ecoregion-already subjected to increased human development and climate change. Of n = 2019 vertebrates observed, 28.5% were roadkill. Increasing urbanization levels were associated with reduced vertebrate abundance on roads and increased road-killed endothermic vertebrates. Traffic volume was strongly associated with reduced vertebrate abundance and increased roadkill; additive effects on roadkill began at approximately 20 vehicles. Daily low temperature and/or relative humidity were also associated with roadkill across vertebrate groups. We provide empirical evidence to understand wildlife-roadkill associations across expanding wildland-urban interfaces to inform effective roadkill mitigation and wildlife conservation management strategies in biodiverse aridland regions. We recommend that managers mitigate or avoid development in rural areas that possess high biodiversity, valuable waterways or migration corridors, and populations of vulnerable species.

Career trajectories, transition rates, and birthdate distributions: the rocky road from youth to senior level in men's European football.

This study aimed to assess youth-to-senior transition rates, quantify the magnitude of relative age effect (RAEs), and evaluate how RAEs affect these transitions in 9,527 men's national football players of England, France, Germany, Italy, and Spain. Regardless of national team, only -15%, 25%, and 40% of U17, U19, and U21 players successfully transitioned to the senior team, respectively, whilst -14%-24% progressed to senior level without being selected during youth. Data suggested a skewed birthdate distribution favouring relatively older players at U17, U19, and U21 levels across all countries, whereas RAEs were also present in England, Italy, and Spain at senior level. Youth-to-senior transition rates were modulated by birthdate at U17 and U19, whereby Q4 players were -2 and 1.5 times more likely to successfully transition at senior level than Q1 players, respectively. Selection at youth international level does not guarantee selection at senior level, but does make it more likely. Moreover, relatively younger athletes are disadvantaged in youth categories, although are more likely to transition to senior level once they have entered the pathway.

hnRNPs: roles in neurodevelopment and implication for brain disorders.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a family of multifunctional RNA-binding proteins able to process nuclear pre-mRNAs into mature mRNAs and regulate gene expression in multiple ways. They comprise at least 20 different members in mammals, named from A (HNRNP A1) to U (HNRNP U). Many of these proteins are components of the spliceosome complex and can modulate alternative splicing in a tissue-specific manner. Notably, while genes encoding hnRNPs exhibit ubiquitous expression, increasing evidence associate these proteins to various neurodevelopmental and neurodegenerative disorders, such as intellectual disability, epilepsy, microcephaly, amyotrophic lateral sclerosis, or dementias, highlighting their crucial role in the central nervous system. This review explores the evolution of the hnRNPs family, highlighting the emergence of numerous new members within this family, and sheds light on their implications for brain development.

Perceptions of Communities of Practice and Sense of Belonging: Focus Groups of Academic Pediatric Faculty.

BACKGROUND: Providing the opportunity for collaboration around a central purpose to improve skills and exchange knowledge, the Community of Practice model can be useful for faculty development. A sense of belonging enhances the engagement in communities. Yet, the barriers and contributors to academic medicine faculty's sense of belonging in communities are not as well explored. METHODS: Through focus groups with 21 academic pediatric faculty conducted between January and March 2023, this qualitative study examined knowledge of Communities of Practice and the factors that affect sense of belonging and engagement. The authors iteratively coded transcripts to generate themes. RESULTS: Community accessibility; opportunities for active engagement; working under a clear, shared purpose; and personal interactions enhanced faculty sense of belonging. Barriers to engagement included competing demands, process challenges, and uncertainty. DISCUSSION: Study results suggest strategies for the promotion of faculty sense of belonging and engagement in Communities of Practice. Consideration of contributors to a sense of belonging may enhance efforts to design and improve engaging faculty development programs.

HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.

Energy metabolism, through pathways such as oxidative phosphorylation (OxPhos) and glycolysis, plays a pivotal role in cellular differentiation and function. Our study investigates the impact of OxPhos disruption in cortical bone development by deleting Mitochondrial Transcription Factor A (TFAM). TFAM controls OxPhos by regulating the transcription of mitochondrial genes. The cortical bone, constituting the long bones' rigid shell, is sheathed by the periosteum, a connective tissue layer populated with skeletal progenitors that spawn osteoblasts, the bone-forming cells. TFAM-deficient mice presented with thinner cortical bone, spontaneous midshaft fractures, and compromised periosteal cell bioenergetics, characterized by reduced ATP levels. Additionally, they exhibited an enlarged periosteal progenitor cell pool with impaired osteoblast differentiation. Increasing Hypoxia-Inducible Factor 1a (HIF1) activity within periosteal cells significantly mitigated the detrimental effects induced by TFAM deletion. HIF1 is known to promote glycolysis in all cell types. Our findings underscore the indispensability of OxPhos for the proper accrual of cortical bone mass and indicate a compensatory mechanism between OxPhos and glycolysis in periosteal cells. The study opens new avenues for understanding the relationship between energy metabolism and skeletal health and suggests that modulating bioenergetic pathways may provide a therapeutic avenue for conditions characterized by bone fragility.

The Gaming Disorder Identification Test (GADIT) - A screening tool for Gaming Disorder based on ICD-11.

Background: Gaming Disorder was included as an addictive disorder in the latest version of the International Classification of Diseases (ICD-11), published in 2022. The present study aimed to develop a screening tool for Gaming Disorder, the Gaming Disorder Identification Test (GADIT), based on the four ICD-11 diagnostic criteria: impaired control, increasing priority, continued gaming despite harm, and functional impairment. Method: We reviewed 297 questionnaire items from 48 existing gaming addiction scales and selected 68 items based on content validity. Two datasets were collected: 1) an online panel (N = 803) from Australia, United States, United Kingdom and Canada, split into a development set (N = 589) and a validation dataset (N = 214); and 2) a university sample (N = 408) from Australia. Item response theory and confirmatory factor analyses were conducted to select eight items to form the GADIT. Validity was established by regressing the GADIT against known correlates of Gaming Disorder. Results: Confirmatory factor analyses of the GADIT showed good model fit (RMSEA=<0.001-0.108; CFI = 0.98-1.00), and internal consistency was excellent (Cronbach's alphas = 0.77-0.92). GADIT scores were strongly associated with the Internet Gaming Disorder Test (IGDT-10), and significantly associated with gaming intensity, eye fatigue, hand pain, wrist pain, back or neck pain, and excessive in-game purchases, in both the validation and the university sample datasets. Conclusion: The GADIT has strong psychometric properties in two independent samples from four English-speaking countries collected through different channels, and shown validity against existing scales and variables that are associated with Gaming Disorder. A cut-off of 5 is tentatively recommended for screening for Gaming Disorder.

A community-academic partnered approach to designing a Virtual Village to address the needs of older adults living with HIV.

ABSTRACTMany older adults living with HIV face unique challenges, including comorbidities, loneliness, and isolation. This community-academic partnered study elicited viewpoints from older adults living with HIV about the characteristics of a digital environment ("Virtual Village") to combat against loneliness and isolation. We utilized Choice-Based Conjoint Analyses to determine preferred attributes of a Virtual Village. We also conducted focus groups and interviews with older adults living with HIV and used an iterative, data-driven approach to systematically identify emergent themes. Participants (N = 82) were aged 50-82 years and racially/ethnically diverse. The majority were men (78%), gay (66%), and lived with HIV for ≥15 years (83%). Cost was the factor that most drove participants' preference for joining a Virtual Village. Thematic concerns included lack of technological confidence, internet access, potential for harassment in digital environments, privacy, and preference for in-person interactions. Praises centered on convenience and making connections across geographic distances. Participants emphasized the need for purposive strategies to form a cohesive and supportive community for older adults living with HIV. A moderated environment was recommneded to create a safe, structured, and comfortable digital environment for older adults living with HIV. A Virtual Village should be viewed as a bridge to in-person interactions.

Does Surgical Intervention Alter the Natural History of Degenerative Rotator Cuff Tears? Comparative Analysis from a Prospective Longitudinal Study.

INTRODUCTION: The natural history of rotator cuff tears often involves progressive pain development, tear enlargement, and advancing muscle fatty degeneration. Both surgery and conservative management have proven to be effective treatments. Our study purpose was to compare the short to mid-term effects of rotator cuff repair on shoulder function, progression of tear size, and muscle degeneration compared to controls with asymptomatic tears that developed pain and were managed nonoperatively. METHODS: This comparative study consists of two separate longitudinal study arms. The control group consisted of asymptomatic degenerative cuff tears followed until pain development and then managed nonoperatively with continued surveillance. The surgical group consisted of subjects with degenerative tears that failed nonoperative treatment and underwent surgical intervention with a minimum of 2 years follow-up. Outcomes included VAS pain, ASES, AROM, strength, and ultrasonography. RESULTS: There were 83 controls and 65 surgical shoulders. The surgical group was younger at enrollment (58.9±5.3 yr vs. 61.2±7.8 yr, p=0.04). The median follow-up for control subjects after pain development was 5.1 years (IQR 3.6) and the median postoperative follow-up for the surgical group was 3.0 years (IQR 0.2). Baseline tear widths (median 14 mm, IQR 9 vs. 13 mm, IQR 8; p=0.45) and tear lengths (median 14 mm, IQR 13 vs. median 11 mm, IQR 8; p=0.06) were similar between the surgical group and controls. There were no differences in the baseline prevalence of fatty degeneration of the supraspinatus or infraspinatus muscles between groups (p=0.43 and p=0.58, respectively). At final follow-up, the surgical group demonstrated significantly lower VAS pain (0 [IQR 2] vs. 3.5 [IQR 4], p=0.0002), higher composite ASES (95 [IQR 13] vs. 65.8 [IQR 32], p=0.0002) and ADL scores (29 [IQR 4] vs. 22 [IQR 8], p=0.0002), greater abduction strength (69.6 N [SD 29] vs. 35.9 N [SD 29], p=0.0002), greater active forward elevation (155˚ [SD 8] vs. 142˚ [SD 28], p=0.002), greater active external rotation in abduction (mean 98.5˚, SD 12 vs. mean 78.2˚, SD 20; p=0.0002) compared to controls. Additionally, the prevalence of fatty muscle degeneration was lower in the surgical group for the supraspinatus and infraspinatus (25% vs. 41%, p=0.05; 17% vs. 34%, p=0.03; respectively). CONCLUSION: This prospective longitudinal study comparing a surgical cohort undergoing rotator cuff repair with a control group treated nonoperatively supports the notion that surgical intervention has the potential to alter the early natural history of degenerative rotator cuff disease. Patients in the surgical group demonstrated clinically relevant differences in pain and functional outcomes. Surgical intervention was protective against progressive muscle degeneration compared to nonoperative treatment.

The safety of recombinant human hyaluronidase PH20 in nonclinical models: An overview of toxicology, pharmacology, and impact of anti-PH20 antibodies.

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for therapeutically relevant doses of rHuPH20.

Evidence that the StlA polyketide synthase is required for the transition of growth to development in Polysphondylium violaceum.

The social amoeba Polysphondylium violaceum uses chemoattractants different from those of Dictyoctelium discoideum for cell aggregation. However, the detailed mechanisms in P. violaceum remain unknown. We have previously reported that the polyketide synthase StlA is involved in inducing aggregation in this species. To elucidate the mechanism of StlA-induced aggregation in P. violaceum, we analysed the phenotype of Pv-stlA- mutants in more detail. Unlike our previous results, the mutant cells did not exhibit proper chemotaxis towards glorin. Defective aggregation was not restored by glorin pulses, 8Br-cAMP, or deletion of the homologue of PufA that is a translational repressor of PKA, whereas mutant cells grown in the presence of 4-methyl-5-pentylbenzene-1,3-diol (MPBD), the putative Pv-StlA product, aggregated normally without it after starvation. Furthermore, the early developmental marker gene, dscA, was down-regulated in the mutant cells. Our data thus suggested that StlA is required for the transition from growth to development in P. violaceum.

Reliability and validity of a measure of service providers' perceptions of child and parent engagement in pediatric rehabilitation therapy sessions.

BACKGROUND: There is growing interest in client engagement in pediatric rehabilitation. This article investigated the psychometric properties of a measure of service providers' perceptions of the affective, cognitive and behavioural engagement of both children with disabilities and their parents in pediatric rehabilitation therapy sessions. METHODS: Test-retest reliability of the Pediatric Rehabilitation Intervention Measure of Engagement-Service Provider version (PRIME-SP) was examined using engagement ratings made by 60 service providers for 77 children and 73 parents. Construct validity was examined using the known-group validity technique, utilizing service providers' ratings of the engagement of parents and their children attending the same session with the service provider. We hypothesized that there would be significantly different, yet moderately correlated engagement ratings for children and their parents. RESULTS: There was evidence of moderate test-retest reliability for the child ratings, indicative of dynamicity across occasions, but also a degree of consistency, as aligned with our expectations. Service providers' ratings of parent and child engagement were not significantly correlated and paired t-tests indicated significantly higher engagement scores for parents than children. CONCLUSIONS: The study provides preliminary evidence to support the reliability and validity of the PRIME-SP as a tool for service providers to document, reflect on and monitor child and/or parent engagement.

Validation of Serbian version of the LittlEARS® Early Speech Production Questionnaire for the assessment of early language development in typically developing children.

OBJECTIVE: The LittlEARS® Early Speech Production Questionnaire (LEESPQ) was developed to provide professionals with valuable information about children's earliest language development and has been successfully validated in several languages. This study aimed to validate the Serbian version of the LEESPQ in typically developing children and compare the results with validation studies in other languages. METHODS: The English version of the LEESPQ was back-translated into Serbian. Parents completed the questionnaire in paper or electronic form either during the visit to the paediatric clinic or through personal contact. A total of 206 completed questionnaires were collected. Standardized expected values were calculated using a second-order polynomial model for children up to 18 months of age to create a norm curve for the Serbian language. The results were then used to determine confidence intervals, with the lower limit being the critical limit for typical speech-language development. Finally, the results were compared with German and Canadian English developmental norms. RESULTS: The Serbian LEESPQ version showed high homogeneity (r = .622) and internal consistency (α = .882), indicating that it almost exclusively measures speech production ability. No significant difference in total score was found between male and female infants (U = 4429.500, p = .090), so it can be considered a gender-independent questionnaire. The results of the comparison between Serbian and German (U = 645.500, p = .673) and Serbian and English norm curves (U = 652.000, p = .725) show that the LEESPQ can be applied to different population groups, regardless of linguistic, cultural or sociological differences. CONCLUSION: The LEESPQ is a valid, age-dependent and gender-independent questionnaire suitable for assessing early speech development in children aged from birth to 18 months.

Modelling Alternative Economic Incentive Schemes for Semi-Natural Grassland Conservation in Estonia.

Semi-natural grasslands (SNGLs) in Estonia are threatened by abandonment. This threat is leading to concerns about the degradation of biodiversity within grassland communities. Despite the high relevance of economic incentives in this context, how such incentives influence land managers' decision-making regarding the agricultural use of SNGLs has not been investigated. To obtain its socio-ecological implications for policy-making, we developed regionally specific agricultural scenarios (compensation payments, livestock capacity, hey export, and bioenergy production) and an interdisciplinary modelling approach that made it possible to simulate agricultural land use changes through land managers' responses to varied economic conditions. Through this approach, we found that some economic factors hampered the use of SNGLs: the moderate profitability of beef production, labour shortages, and the relatively high profitability of mulching. We observed a positive relationship between SNGLs and habitat suitability for breeding and feeding birds. However, due to the high maintenance costs of SNGLs, the modelling results indicated that increasing the use of SNGLs through public budgets caused crowding-out effects, i.e., the deteriorating market integration of regional agriculture. This study emphasises the need for policy measures aimed at cost-effective, labour-efficient management practices for SNGLs.