The Hierarchical Coevolutionary Units of Ecological Networks.

In ecological networks, cohesive groups of species may shape the evolution of interactions, serving as coevolutionary units. Ranging across network scales, from motifs to isolated components, elucidating which cohesive groups are more determinant for coevolution remains a challenge in ecology. We address this challenge by integrating 376 empirical mutualistic and antagonistic networks and coevolutionary models. We identified cohesive groups at four network scales containing a significant proportion of potential direct coevolutionary effects. Cohesive groups displayed hierarchical organisation, and potential coevolutionary effects overflowing lower-scale groups were contained by higher-scale groups, underscoring the hierarchy's impact. However, indirect coevolutionary effects blurred group boundaries and hierarchy, particularly under strong selection from ecological interactions. Thus, under strong selection, indirect effects render networks themselves, and not cohesive groups, as the likely coevolutionary units of ecological systems. We hypothesise hierarchical cohesive groups to also shape how other forms of direct and indirect effects propagate in ecological systems.

Direct and indirect effects of copepod grazers on community structure.

Ecological theory and empirical research show that both direct lethal effects and indirect non-lethal effects can structure the composition of communities. While the direct effects of grazers on marine phytoplankton communities are well studied, their indirect effects are still poorly understood. Direct and indirect effects are inherently difficult to disentangle in plankton food webs. In this study we evaluate the indirect effects of copepod grazers on community function and structure using isolated chemical alarm signals, copepodamides. We expose intact summer and spring communities to direct grazing from copepods, or to chemical alarm cues without the presence of grazers in controlled experiments. The effects of direct grazing on ecosystem function were moderate in both experiments as indicated by levels of chlorophyll and primary production. Indirect and direct effects resulted in changes in the composition of both the eukaryote and prokaryote communities as shown by metabarcoding of 18S and 16S rRNA. Size structure analysis suggests that direct grazing and copepodamide exposure both favoured smaller organisms (< 10-15 µm) corroborating the size-structuring effect of copepod grazers. We conclude that the well-established effect of copepods on phytoplankton communities results from a combination of direct and indirect effects. This is a first attempt to isolate indirect effects of copepods on community structure and the results suggest that a full mechanistic understanding of the structuring effect of copepods will require insights to both direct and indirect effects of consumers as demonstrated for other ecosystems components.

Benefits and costs of measures to tackle the outbreak of African swine fever in Sweden.

A common rule in many countries for mitigating the damage caused by African swine fever (ASF) is to eradicate the virus at the outbreak in order to prevent its dispersal and the associated social costs of depopulating infected domestic pigs. The economic performance of this practice, as measured by five different evaluation criteria (net present value, benefit-cost ratio, rate of return, internal rate of return, and payback time), depends on the type of control cost and the spatial and dynamic allocation of benefits, i.e. avoided losses from infected domestic pig farms. The present paper calculates the direct and indirect costs of immediate control measures during an ASF outbreak in wild boars in Mid Sweden. The direct costs include expenses incurred for surveillance, laboratory tests, depopulation of wild boar etc., while the indirect costs are borne by firms and people in the area in relation to movement restrictions. The calculations showed that the total cost of control measures amounted to 28 million euros, with indirect costs making up 40 % of this figure. The benefits were greatly dependent on the speed of ASF dispersal and assumptions about pig farmers' investment responses, which implied large variations in each of the five evaluation criteria.

Serosurvey and associated risk factors for bovine viral diarrhea virus infection in cattle in Egypt.

Bovine viral diarrhea virus (BVDV), is widely spread, poses a considerable risk of infection in the majority of dairy farms, causing respiratory, gastrointestinal, and reproductive problems. The aim of this study was to determine the seroprevalence and the risk variables associated with the seroprevalence of BVDV infection in cattle in four Egyptian governorates. A total of 680 blood samples were collected from cattle and examined for the presence of antibodies against BVDV using indirect ELISA (iELISA). Reproductive and management factors were considered, and epidemiological surveys were conducted. The total seroprevalence of BVDV in cattle was 18.24% (124/680) and it was significantly higher in females 19.66% (116/590), cattle older than 8 years 22.14% (62/280), dairy animals 22.65% (94/514), introduction of new animals to herd 21.39% (89/416), breeding with artificial insemination 28.46% (74/260), animals with history of abortion 28.76% (49/357), or during lactation stage 23% (89/387). The present findings suggest that BVD is prevalent in Egyptian dairy cattle and has an impact on farm productivity and production. Therefore, older, lactating, and aborted animals should also be identified for the disease, pose a risk of infection, and be handled appropriately.

Indirect estimation of the prevalence of type 2 diabetes mellitus in the sub-population of Tehran: using non-laboratory risk-score models in Iran.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) in the population covered by the Tehran University of Medical Sciences is unclear but crucial for healthcare programs. This study aims to validate four non-laboratory risk-score models, the American Diabetes Association (ADA) Risk Score, Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK), Finnish Diabetes Risk Score (FINDRISC), and TOPICS Diabetes Screening Score, for identifying undiagnosed diabetes and indirectly estimate the prevalence of T2DM in a subset of the Tehranian population using the selected model. METHODS: This research consisted of two main parts. In the first part, non-laboratory risk-score models to identify undiagnosed T2DM were validated using Iranian data from STEPs 2016 survey. The model performance was evaluated through the Area Under the Curve (AUC) and calibration via the observed-to-expected (O/E) ratio. Additional independent data from STEPs 2011 survey in Iran were utilized to test the model results by comparing indirect prevalence estimates with observed estimates. In the second part, the prevalence of T2DM was estimated indirectly by applying the selected model to a representative random sample from a Tehranian population telephone survey conducted in 2023. RESULTS: Among the different models used, AUSDRISK showed the best performance in both discrimination (AUC (95% confidence interval (CI)): 0.80 (0.78, 0.81)) and calibration (O/E ratio = 1.01). After updating the original model, there was no change in the AUC value or calibration. Additionally, our findings indicate that the indirect estimates are nearly identical to the observed values in STEPs 2011 survey. In the second part of the study, by applying the recalibrated model to a subsample, the indirect prevalence of undiagnosed diabetes and T2DM (95% CI) were estimated at 4.18% (3.87, 4.49) and 11.1% (9.34, 13.1), respectively. CONCLUSION: Given the strong performance of the model, it appears that indirect method can provide a cost-effective and simple approach to assess disease prevalence and intervention effectiveness.

Evaluation of the accuracy of digital indirect bonding vs. conventional systems: a randomized clinical trial.

OBJECTIVES: To compare the accuracy and chair time of self-ligating brackets using direct bonding, traditional indirect bonding (IB), and computer-aided design/computer-aided manufacturing (CAD/CAM) IB techniques after orthodontic leveling and alignment. MATERIALS AND METHODS: Forty-five patients were randomly assigned to three bonding groups (G1 [n = 15], G2 [n = 15], and G3 [n = 15]). Evaluation after the alignment and leveling phases used two parameters of the objective grading system of the American Board of Orthodontics for root parallelism and posterior marginal ridges, assessed using panoramic radiographies (PR I and PR II), a digital model, and a plaster model. Blinding was only applied for outcome assessment. No serious harm was observed except for gingivitis associated with plaque accumulation. RESULTS: Although G3 showed better numerical results, they were not statistically significant in the radiographic or model evaluations (P > .001). Mean chair time was significantly shorter in G3 (1.1 ± 11.8 min) vs. G1 (56.7 ± 7.3 min) and G2 (52.8 ± 8.3 min; P < .001). CONCLUSIONS: The CAD/CAM IB system for self-ligating brackets was as effective as conventional methods, with a shorter chair time.

Economic and societal burden of myasthenia gravis in Denmark, Finland, and Sweden: A population-based registry study.

BACKGROUND AND PURPOSE: Health care resource utilization (HCRU) and the economic burden of myasthenia gravis (MG) are significant, but existing studies rarely include comprehensive nationwide data. We examined HCRU and direct and indirect costs associated with MG overall and by disease severity in Denmark, Finland, and Sweden. METHODS: Data were collected retrospectively from nationwide health and social care registries. All individuals ≥18 years of age with ≥2 International Classification of Diseases diagnoses of MG between 2000 and 2020 were included. HCRU, direct (inpatient and outpatient contacts, medication) and indirect costs (early retirement, sick leave, death), and associated factors were calculated. RESULTS: The full study cohort comprised 8622 people with MG (pwMG). Mean annual numbers of all-cause secondary health care contacts for pwMG were 3.4 (SD = 8.3), 7.0 (SD = 12.3), and 2.9 (SD = 3.9), with mean annual total costs of €12,185, €9036, and €5997 per person in Denmark, Finland, and Sweden, respectively. Inpatient periods, involving 77%-89% of study participants in the three countries, contributed most to direct costs, whereas the majority of indirect costs resulted from early retirement in Denmark and Finland, and sick leave periods in Sweden. Mean annual total costs were highest with very severe MG (€19,570-€33,495 per person across the three countries). Female sex and comorbidities, such as mental and behavioral disorders and severe infections, were also associated with higher total costs. CONCLUSIONS: This population-based study shows a high level of HCRU and a significant direct and indirect economic burden of MG across three Nordic countries, especially for severe forms of MG.

A Randomized Controlled Clinical Trial of the Performance of Three Bioactive Endodontic Cements in Primary Molar Teeth Diagnosed with Reversible Pulpitis: 1-Year Follow-Up Study.

OBJECTIVES: The objective of this clinical trial was to evaluate and compare the clinical and radiographic successes of three bioactive endodontic cements (BEC) including novel portland cement-based material releasing fluoride, resin-modified silicate glass cement, and pure tricalcium silicate-based cement-in the treatment of primary molars diagnosed with reversible pulpitis via indirect pulp capping. METHODS: Eighty-six (86) participants with previously untreated first and second primary molars were included in this study. The teeth were randomly allocated into three groups: pure tricalcium silicate-based cement, resin-modified silicate glass cement, and novel portland cement-based material releasing fluoride. Cavities were capped with the assigned cement after caries excavation using standard protocols. The teeth that underwent treatment were restored using glass ionomer cement and composite resin. Clinical and radiographic evaluations were performed at 1, 6, and 12 months. The data were analyzed using Pearson chi-square, Kruskal-Wallis H and Z test (P = 0.05). RESULTS: The success rate was 88% (n=25) in the pure tricalcium silicate-based cement group, 88.5% (n=26) in the resin-modified silicate glass cement group, and 100% (n=25) in the novel portland cement-based material releasing fluoride group. The differences at the 1st, 6th, and 12th month follow-up visits were not statistically significant among the groups (P>0.05). No difference was found between the integrity of the resin composite restorations overlying pure tricalcium silicate-based cement, resin-modified silicate glass cement, and novel portland cement-based material releasing fluoride according to the USPHS criteria. CONCLUSIONS: Novel portland cement-based material releasing fluoride can be considered an alternative for preserving the tooth, as it showed a high success rate in treating primary molars diagnosed with reversible pulpitis via indirect pulp capping. CLINICAL SIGNIFICANCE: Novel Portland cement-based material releasing fluoride could be beneficial in the treatment of primary molars diagnosed with reversible pulpitis via indirect pulp capping.

Pisolithus microcarpus isolates with contrasting abilities to colonise Eucalyptus grandis exhibit significant differences in metabolic signalling.

Biotic factors in fungal exudates impact plant-fungal symbioses establishment. Mutualistic ectomycorrhizal fungi play various ecological roles in forest soils by interacting with trees. Despite progress in understanding secreted fungal signals, dynamics of signal production in situ before or during direct host root contact remain unclear. We need to better understand how variability in intra-species fungal signaling at these stages impacts symbiosis with host tissues. Using the ECM model Pisolithus microcarpus, we selected two isolates (Si9 and Si14) with different abilities to colonize Eucalyptus grandis roots. Hypothesizing that distinct early signalling and metabolite profiles between these isolates would influence colonization and symbiosis, we used microdialysis to non-destructively collect secreted metabolites from either the fungus, host, or both, capturing the dynamic interplay of pre-symbiotic signalling over 48 hours. Our findings revealed significant differences in metabolite profiles between Si9 and Si14, grown alone or with a host root. Si9, with lower colonization efficiency than Si14, secreted a more diverse range of compounds, including lipids, oligopeptides, and carboxylic acids. In contrast, Si14's secretions, similar to the host's, included more aminoglycosides. This study emphasizes the importance of intra-specific metabolomic diversity in ectomycorrhizal fungi, suggesting that early metabolite secretion is crucial for establishing successful mutualistic relationships.

The hidden burden of atopic dermatitis in central and Eastern European Countries.

BACKGROUND: Atopic dermatitis (AD) imposes a hidden burden through its negative effects on quality of life and productivity. We aim to estimate this hidden burden in adults and adolescents in Central and Eastern European (CEE) countries. METHODS: We created a burden of disease model to quantify AD's hidden burden. Humanistic burden was calculated by estimating the monetary value of quality-adjusted life years (QALYs) lost, using prevalence data from the Global Burden of Disease study, and gross domestic product (GDP) per capita for each country. Indirect economic burden was estimated based on productivity loss from absenteeism and presenteeism, adjusted for labor force participation and unemployment rates. Total hidden burden was determined by combining productivity losses and QALYs lost. RESULTS: QALY loss due to AD ranged from 1,832 to 58,596 annually in CEE countries, equating to 38 million to approximately 1 billion Euros per country. Productivity losses ranged from 3.6 to 148.9 million Euros annually. The total hidden burden of AD represents 0.11% to 0.43% of the GDP. CONCLUSIONS: Our estimates reflect significant differences in population sizes, prevalence, and economic strength among CEE countries. Adjusting findings to country-specific GDP provided insights into AD's true hidden burden, offering valuable information for decision-making.

Atopic dermatitis (AD), commonly known as eczema, is a widespread skin condition causing itchiness and discomfort. While it's well-known that treating eczema costs money and affects patients' health, there's more to its impact than meets the eye. Our study closely examined eczema's 'hidden' effects in Central and Eastern European (CEE) countries, such as its impact on work ability and life enjoyment.We found that eczema's impact is not just about the direct costs of treatment. It also includes how the condition leads to lost workdays and reduced productivity, and more importantly, how it lowers the quality of life for those who have it. This part of eczema's impact, which isn't always easy to see or measure, can be just as significant.Our research is important because it shows that when health officials and policymakers think about how to deal with eczema, they need to consider these hidden effects too. Different countries in Central and Eastern Europe experience these effects in varying degrees. By understanding this, healthcare systems can make better decisions about where to put their healthcare resources. For example, they might decide to invest more in treatments or support that can improve the quality of life for people with eczema.In summary, our study highlights the need to look at the full picture of eczema's impact. This includes not only the costs of treatment but also how it affects people's lives in ways that are not always immediately obvious.

Optimal tactics for surgical revascularisation in diabetic angiopathy of the lower limbs.

OBJECTIVE: Aim: This study aims to compare the efficacy of conservative treatment methods versus advanced surgical interventions, including revascularising automyelotransplantation and stem cell therapy, in improving vascular patency and the quality of life in patients with diabetic angiopathy. PATIENTS AND METHODS: Materials and Methods: The research analyzed 68 patients with angiopathies under medical supervision from January 2007 to December 2017 at the National Scientific Center of Surgery named after A.N. Syzganov. Participants, aged 4 to 49, were divided into two groups based on angiographic blood flow characteristics: one with accelerated and another with delayed blood flow. A comprehensive participant selection process was implemented to ensure a representative sample. Sensitivity analysis was conducted to validate the findings' robustness. RESULTS: Results: The main group demonstrated notable success in limb salvage, with 90.9% avoiding high limb amputation post-revascularising automyelotransplantation. Moreover, 16.7% of patients experienced healing of trophic ulcers and toe necrosis. The use of stem cells from adipose tissue and fetal tissue progenitor cells showed promising results in reducing pain and increasing pain-free walking distance, alongside the formation of collateral vascular networks. CONCLUSION: Conclusions: The study concludes that advanced surgical interventions and stem cell therapies significantly enhance treatment outcomes in patients with diabetic angiopathy compared to conventional conservative treatments. These findings highlight the potential of personalized and innovative approaches in managing vascular complications associated with diabetes, offering new avenues for reducing disability and improving patient quality of life. Future research should focus on further refining these therapeutic strategies and exploring their integration into clinical practice.

Is bracket bonding with guided bonding devices accurate enough for crowded dentition?

BACKGROUND: This research aimed to study whether bracket bonding using guided bonding devices (GBDs) is accurate enough for crowded dentitions in vitro. METHODS: Fifteen three-dimensionally (3D) printed resin model sets were included and divided into three groups: mild, moderate, and severe crowding. The resin models were scanned and virtually bonded with brackets. Corresponding GBDs were generated and 3D printed. Subsequently, the brackets were bonded to the resin models on a dental mannequin using the GBDs. The models with bonded brackets were scanned, and comparisons were made between the positions of the actually bonded and the planned ones to evaluate possible deviations. RESULTS: There was no immediate bonding failure in any group. The bonding duration tended to increase with crowding severity (P > 0.05). Almost all linear and angular deviations in all groups were below 0.5 mm and 2°, respectively, and no statistically significant difference was found among the different crowding degrees (P > 0.05). In all groups, the brackets tended to deviate lingually and had buccal crown torque. Brackets in the groups with mild and severe crowding showed a tendency for mesiobuccal rotation. CONCLUSION: GBDs provide high bracket bonding accuracy for dentitions with different crowding degrees and, thus, could hopefully be applied to uncrowded and crowded dentitions alike.

Our Experience With 200 Cases of Inguinal Hernia Repair Using the Dynamic Self-Adjusting Prosthesis: A Case Series and Literature Review.

Introduction Inguinal hernioplasty (IH) is one of the most frequently performed surgical procedures globally. Today, a variety of surgical techniques and prosthesis types are available for this procedure. Methods At our center, we performed 200 inguinal hernioplasties using the dynamic self-adjusting prosthesis (protesi autoregolantesi dinamica, PAD) from May 1, 2022, to May 31, 2023. Our objective was to retrospectively analyze the outcomes and compare them with the current scientific literature on this surgical technique. Results Our results align with those reported by other authors using the same surgical technique. With the PAD technique, we assessed the type and frequency of adverse events up to 12 months following IH. All patients were male, with an average BMI of 26.6. Among the 200 hernias, 99 were right-sided, 101 were left-sided, 63 were direct, and 137 were indirect. The average length of hospitalization was one day. The most common postoperative complication was hematoma near the surgical site, but no prosthesis displacement was observed. In 71% of patients, analgesics were discontinued within 24 hours. The outcomes of our study are comparable to those reported by the inventor of this surgical technique. Conclusion The procedure has demonstrated safety and effectiveness and could serve as a viable alternative to traditional IH techniques.

Recognising Potential Ambiguities in Measurements of Oxygen in Tissues.

Measuring oxygen (O2) in tissues has been a central theme of the International Society on Oxygen Transport to Tissue (ISOTT) since its founding 50 years ago in 1973. The initial presentations by many distinguished members reflect this focus and demonstrate the importance of the contributions of the members of ISOTT. This paper considers their work and its legacy in the context of the continuing challenges of making meaningful measurements of O2 in tissue. Because many technical, physiological, and pathophysiological factors are directly or implicitly involved in obtaining any measured value of O2 in living tissues, interpretations of what the measured value represents and its biological implications need to take these factors into account. The challenges arise from two very simple but painfully true factors that make it challenging to obtain measurements of O2 in tissues in vivo that are useful for the understanding of physiological and pathophysiological processes. First, throughout the volume of functioning tissue that is assessed by any technique, there is a complex spatial heterogeneity of O2 levels. No technique can usually fully represent this complexity in a given measurement, because the heterogeneity extends from the environment in the tissue surrounding cells to variations within the cell. Therefore, the value of the output from a measurement inevitably consists of a complex, averaged summary of O2 in the tissue. Second, the levels of O2 are constantly changing in living tissues (variations occur in seconds, minutes, hours, and/or days and differ by location) at rates that are difficult to resolve for available techniques, because they occur faster than data acquisition time and/or cannot be used as frequently as needed to follow the longer-term changes. However, as demonstrated in research reported in the publications from ISOTT, studies of O2 in tissue, in spite of the potential ambiguities in the measured values, can provide very valuable insights into physiology and pathophysiology. This is most likely to occur if researchers explicitly recognise why and how their measurement does not fully portray the complexity of O2. When measurements can be repeated, the resulting change between measurements provides information about the dynamics of the physiology and pathophysiology. Assessing change in O2 levels can also provide evidence about responses to treatments. Similarly, finding evidence of hypoxia, even though it does not capture the heterogeneity and dynamics actually happening in the tissue, can still inform clinical care if the measurement is well-understood.

Indirect social influence and diffusion of innovations: An experimental approach.

A fundamental feature for understanding the diffusion of innovations through a social group is the manner in which we are influenced by our own social interactions. It is usually assumed that only direct interactions, those that form our social network, determine the dynamics of adopting innovations. Here, we test this assumption by experimentally and theoretically studying the role of direct and indirect influences in the adoption of innovations. We perform experiments specifically designed to capture the influence that an individual receives from their direct social ties as well as from those socially close to them, as a function of the separation they have in their social network. The results of 21 experimental sessions with more than 590 participants show that the rate of adoption of an innovation is significantly influenced not only by our nearest neighbors but also by the second and third levels of influences an adopter has. Using a mathematical model that accounts for both direct and indirect interactions in a network, we fit the experimental results and determine the way in which influences decay with social distance. The results indicate that the strength of peer pressure on an adopter coming from its second and third circles of influence is approximately two-third and one-third, respectively, relative to their closest neighbors. Our results strongly suggest that the adoption of an innovation is a complex process in which an individual feels significant pressure not only from their direct ties but also by those socially close to them.

Indirect costs assessment and intangible costs description of rheumatoid arthritis patients with biological therapy in Morocco: ECORAM Study.

INTRODUCTION: The aims of study are to estimate the indirect costs and intangible costs of RA in Morocco and to identify the factors likely to influence these costs among suffering patients. METHODS: In the current study, data were collected by face-to-face interviews using a questionnaire in addition to the patient's files. Indirect costs including productivity losses and formal care, and intangible costs such as the cessation of physical and leisure activities, family care and divorce or remaining single until menopause's age for women due to the disease were reported for 110 RA patients. RESULTS: The results show that among patients who lost totally or partially their salary, the annual average costs is $2337.73 ± 1649.80 per patient, with a minimum and a maximum of $600 and $9630 respectively. As regards formal care, only 13 patients reported that they paid for care services; the annual average cost was $421.84 ± 261.34 with a minimum of $252 and a maximum of $1200. Statistical analysis revealed significant differences between annual lost salary and gender (p = .04) disease duration (p = .016) and sport/leisure activities cessation (p = .08). CONCLUSION: Besides the burden in terms of productivity loss and caregivers' costs, the intangible costs are considerable, especially those related to divorce and spinsterhood. These conclusions may contribute to the understanding of the socio-economic impact of the disease and to the development of strategies for better governance of RA in Morocco.

Mapping the Evidence for Measuring Energy Expenditure and Indicating Hypermetabolism in Motor Neuron Disease: A Scoping Review.

OBJECTIVE: To map the international methods used to measure energy expenditure of adults living with motor neuron disease (MND) and to highlight discrepancies when indicating hypermetabolism in the MND literature. BACKGROUND: A decline in the nutritional status of patients is associated with exacerbated weight loss and shortened survival. Assessments of energy expenditure, using a variety of methods, are important to ensure an adequate energy intake to prevent malnutrition-associated weight loss. Assessments of energy expenditure are also commonly used to indicate hypermetabolism in MND, although these approaches may not be optimal. METHODS: A protocol based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews Guidelines was developed. Three electronic databases (Medline [Ovid], CINAHL [EBSCO], and Web of Science) were exhaustively searched. Identified publications were systematically screened according to predefined PICOS eligibility criteria. The primary outcome was the identification of methods used to measure energy expenditure in MND. The secondary outcome was the identification of applications of energy expenditure assessments to indicate hypermetabolism in MND. RESULTS: Thirty-two observational primary research publications were identified. Thirteen (40.6%) were longitudinal in design, with data on repeated measurements of energy expenditure presented in 3 (9.4%). Thirteen (40.6%) were case-control studies, of which 11 use a matched control group. Pulmonary function was used to assess eligibility in 10 publications. Energy expenditure was measured using indirect calorimetry (IC) in 31 studies. Discrepancies in the durations of fasted, measurement, and washout periods were observed. Of all included publications, 50% used assessments of resting energy expenditure to identify hypermetabolism. Bioelectrical impedance analysis was used to assess body composition alongside energy expenditure in 93.8% of publications. CONCLUSIONS: Resting energy expenditure is most frequently measured using an open-circuit IC system. However, there is a lack of a standardized, validated protocol for the conduct and reporting of IC and metabolic status in patients with MND.

Phenology mediates direct and indirect interactions among co-occurring invasive plant species.

Why nonnative invasive plant species commonly co-occur, despite their competitive superiority and propensity to displace native species, remains a paradox in invasion biology. Negative interactions among competitively dominant invaders are potentially alleviated by two understudied mechanisms: seasonal priority effects, where phenological separation weakens the effect of competition on species with early phenology; and indirect facilitation, where competition between two species is mitigated by a third species. Although phenological separation has been speculated as a mechanism for explaining co-occurrence patterns of invasive plants, it has never been directly tested. In a greenhouse experiment, we tested the effect of phenological separation on direct and indirect interactions between three co-occurring invasive plant species found in the riparian forests of North America. These species have distinct natural phenological separation with reproduction in early spring (Ficaria verna), mid-spring (Alliaria petiolata), and late summer (Microstegium vimineum). When phenology was experimentally synchronized, direct pairwise interactions among invasive species were overwhelmingly negative, asymmetric, and unlikely to promote co-occurrence. However, increasing phenological separation generated seasonal priority effects, which weakened the effect of competition on species with early phenology. Furthermore, the addition of a third species generated indirect facilitative effects, which balanced competitive outcomes among the two weakest competitors. Based on these findings, we conclude that phenological separation modulates the strength of both seasonal priority effects and indirect facilitation within species interaction networks and may promote the co-occurrence of three common invasive species within this study system. We articulate how future studies can test the external validity of these findings in more complex environmental conditions and with a larger range of invasive plants.

An improvement in the method of correcting indirect radial strain measurements during triaxial strength tests in rocks.

The present article provides an improvement in the method to correct indirect strain measurements in triaxial compressive strength tests through axial displacement and hydraulic fluid volume change measurements. The improvement focused on reducing the parameters of the formula proposed for indirect volumetric strain in the original method, thereby facilitating the development of a simpler formula in which the radial strain depends on only two parameters: the initial volume of the rock specimen and the volume changes of the hydraulic fluid for each instant. The comparison between the improvement proposed, and original method resulted in a mean absolute difference of 0.003.•This improvement does not depend on the axial strain, unlike the original method, which requires correcting the indirect axial strain measurements before correcting the indirect radial strain measurements.•This improvement can be useful for research on the stress-strain behavior of intact rock under laboratory conditions, such as in the study of the post-peak state.

Efficacy and Safety of Somapacitan Relative to Somatrogon and Lonapegsomatropin in Pediatric Growth Hormone Deficiency: Systematic Literature Review and Network Meta-analysis.

INTRODUCTION: Since direct comparisons of long-acting growth hormones (LAGHs) are lacking, analyses were performed to indirectly compare the efficacy and safety of somapacitan versus somatrogon and lonapegsomatropin in children with growth hormone deficiency (GHD). METHODS: A systematic literature review (SLR) identified studies of once-weekly LAGHs for the treatment of pediatric GHD. Indirect comparisons (ICs) using a Bayesian hierarchical network meta-analysis and a random effects model were performed using daily growth hormone (GH) 0.034 mg/kg/day (base case) or 0.024-0.034 mg/kg/day (alternative analyses) as the common comparator to compare height outcomes to 52 weeks [annualized height velocity, height velocity standard deviation score (SDS), and height SDS]. Identified evidence did not allow IC of safety or longer-term efficacy outcomes so these were qualitatively described. RESULTS: The SLR identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only), and one lonapegsomatropin trial comparing the LAGH with daily GH in treatment-naïve pre-pubertal children for IC. ICs revealed no differences at 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH, with respect to all growth outcomes considered in children with GHD. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily GH, with the exception of observed injection site pain for somatrogon. CONCLUSION: No efficacy and safety differences were identified in comparisons of once weekly somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH. All treatments were generally well tolerated, with the exception of observed injection site pain for somatrogon.

It is valuable to compare similarly acting treatments to determine their relative benefits and risks. Direct comparisons of long-acting growth hormones (LAGHs) are lacking, so analyses were performed to indirectly compare the efficacy and safety of the LAGH somapacitan versus the LAGHs somatrogon and lonapegsomatropin in children with growth hormone deficiency. Studies of once-weekly LAGHs for the treatment of pediatric growth hormone deficiency were identified using a systematic literature review, then the data obtained were indirectly compared using standard statistical methods with daily growth hormone 0.034 mg/kg/day (base case) or 0.024­0.034 mg/kg/day (alternative analyses) as the common comparator. Height outcomes to 52 weeks (annualized height velocity, height velocity standard deviation score, and height standard deviation score) were compared between treatments. Sufficient information to allow indirect comparison of safety or longer-term efficacy outcomes were not found so these were qualitatively described. The systematic literature review identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only) and one lonapegsomatropin trial comparing the LAGH with daily growth hormone in previously untreated pre-pubertal children for inclusion in the indirect comparison. Indirect comparisons identified no differences to 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily growth hormone, with respect to all growth outcomes considered in children with growth hormone deficiency. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily growth hormone, with the possible exception of injection site pain with somatrogon.