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PurposeIn children with cerebral palsy, flexion deformities of the knee can be treated with a distal femoral extension osteotomy combined with either patellar tendon advancement or patellar tendon shortening. The purpose of this study was to establish a consensus through expert orthopedic opinion, using a modified Delphi process to describe the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. A literature review was also conducted to summarize the recent literature on distal femoral extension osteotomy and patellar tendon shortening/patellar tendon advancement.MethodA group of 16 pediatric orthopedic surgeons, with more than 10 years of experience in the surgical management of children with cerebral palsy, was established. The group used a 5-level Likert-type scale to record agreement or disagreement with statements regarding distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. Consensus for the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening was achieved through a modified Delphi process. The literature review, summarized studies of clinical outcomes of distal femoral extension osteotomy/patellar tendon shortening/patellar tendon advancement, published between 2008 and 2022.ResultsThere was a high level of agreement with consensus for 31 out of 44 (70%) statements on distal femoral extension osteotomy. Agreement was lower for patellar tendon advancement/patellar tendon shortening with consensus reached for 8 of 21 (38%) of statements. The literature review included 25 studies which revealed variation in operative technique for distal femoral extension osteotomy, patellar tendon advancement, and patellar tendon shortening. Distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening were generally effective in correcting knee flexion deformities and extensor lag, but there was marked variation in outcomes and complication rates.ConclusionThe results from this study will provide guidelines for surgeons who care for children with cerebral palsy and point to unresolved questions for further research.Level of evidencelevel V.

BACKGROUND: Rapid diagnostic tests (RDTs) that rely on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) have become key tools for diagnosing P. falciparum infection. The utility of RDTs can be limited by PfHRP2 persistence, however it can be a potential benefit in low transmission settings where detection of persistent PfHRP2 using newer ultra-sensitive PfHRP2 based RDTs can serve as a surveillance tool to identify recent exposure. Better understanding of the dynamics of PfHRP2 over the course of a malaria infection can inform optimal use of RDTs. METHODS: A previously published mathematical model was refined to mimic the production and decay of PfHRP2 during a malaria infection. Data from 15 individuals from volunteer infection studies were used to update the original model and estimate key model parameters. The refined model was applied to a cohort of patients from Namibia who received treatment for clinical malaria infection for whom longitudinal PfHRP2 concentrations were measured. RESULTS: The refinement of the PfHRP2 dynamic model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 33.6 × 10-15 g (95% CI 25.0-42.1 × 10-15 g) of PfHRP2 in vivo per parasite replication cycle, with an elimination half-life of 1.67 days (95% CI 1.11-3.40 days). The refined model included these updated parameters and incorporated individualized body fluid volume calculations, which improved predictive accuracy when compared to the original model. The performance of the model in predicting clearance of PfHRP2 post treatment in clinical samples from six adults with P. falciparum infection in Namibia improved when using a longer elimination half-life of 4.5 days, with 14% to 67% of observations for each individual within the predicted range. CONCLUSIONS: The updated mathematical model can predict the growth and clearance of PfHRP2 during the production and decay of a mono-infection with P. falciparum, increasing the understanding of PfHRP2 antigen dynamics. This model can guide the optimal use of PfHRP2-based RDTs for reliable diagnosis of P. falciparum infection and re-infection in endemic settings, but also for malaria surveillance and elimination programmes in low transmission areas.

PurposeThe purpose of this study was to establish consensus for the assessment of foot alignment and function in ambulatory children with cerebral palsy, using expert surgeon's opinion through a modified Delphi technique.MethodsThe panel used a five-level Likert-type scale to record agreement or disagreement with 33 statements regarding the assessment of foot alignment and function. Consensus was defined as at least 80% of responses being in the highest or lowest of two of the five Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached.ResultsConsensus was achieved for 25 (76%) statements, general agreement for 4 (12%) statements, and lack of consensus for 4 (12%) of the statements. There was consensus that the functional anatomy of the foot is best understood by dividing the foot into three segments and two columns. Consensus was achieved concerning descriptors of foot segmental alignment for both static and dynamic assessment. There was consensus that radiographs of the foot should be weight-bearing. There was general agreement that foot deformity in children with cerebral palsy can be classified into three levels based on soft tissue imbalance and skeletal malalignment.ConclusionThe practices identified in this study can be used to establish best care guidelines, and the format used will be a template for future Delphi technique studies on clinical decision-making for the management of specific foot segmental malalignment patterns commonly seen in children with cerebral palsy.Level of evidenceV.

PurposeThere is marked variation in indications and techniques for hamstring surgery in children with cerebral palsy. There is particular uncertainty regarding the indications for hamstring transfer compared to traditional hamstring lengthening. The purpose of this study was for an international panel of experts to use the Delphi method to establish consensus indications for hamstring surgery in ambulatory children with cerebral palsy.MethodsThe panel used a five-level Likert-type scale to record agreement or disagreement with statements regarding hamstring surgery, including surgical indications and techniques, post-operative care, and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest two ratings. There was no agreement if neither of these thresholds was reached.ResultsThe panel reached consensus or general agreement for 38 (84%) of 45 statements regarding hamstring surgery. The panel noted the importance of assessing pelvic tilt during gait when considering hamstring surgery, and also that lateral hamstring lengthening is rarely needed, particularly at the index surgery. They noted that repeat hamstring lengthening often has poor outcomes. The panel was divided regarding hamstring transfer surgery, with only half performing such surgery.ConclusionThe results of this study can help pediatric orthopedic surgeons optimize decision-making in their choice and practice of hamstring surgery for ambulatory children with cerebral palsy. This has the potential to reduce practice variation and significantly improve outcomes for ambulatory children with cerebral palsy.Level of evidencelevel V.

PurposeThe purpose of this study was to develop consensus for the surgical indications of anterior distal femur hemiepiphysiodesis in children with cerebral palsy using expert surgeon opinion through a modified Delphi technique.MethodsThe panel used a 5-level Likert-type scale to record agreement or disagreement with 27 statements regarding anterior distal femur hemiepiphysiodesis. Consensus was defined as at least 80% of responses being in the highest or lowest 2 of the Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest 2 ratings.ResultsFor anterior distal femur hemiepiphysiodesis, 27 statements were surveyed: consensus or general agreement among the panelists was achieved for 22 of 27 statements (22/27, 82%) and 5 statements had no agreement (5/27, 18%). There was general consensus that anterior distal femur hemiepiphysiodesis is indicated for ambulatory children with cerebral palsy, with at least 2 years growth remaining, and smaller (

Atmospheric rivers (ARs) generate most of the economic losses associated with flooding in the western United States and are projected to increase in intensity with climate change. This is of concern as flood damages have been shown to increase exponentially with AR intensity. To assess how AR-related flood damages are likely to respond to climate change, we constructed county-level damage models for the western 11 conterminous states using 40 years of flood insurance data linked to characteristics of ARs at landfall. Damage functions were applied to 14 CMIP5 global climate models under the RCP4.5 "intermediate emissions" and RCP8.5 "high emissions" scenarios, under the assumption that spatial patterns of exposure, vulnerability, and flood protection remain constant at present day levels. The models predict that annual expected AR-related flood damages in the western United States could increase from $1 billion in the historical period to $2.3 billion in the 2090s under the RCP4.5 scenario or to $3.2 billion under the RCP8.5 scenario. County-level projections were developed to identify counties at greatest risk, allowing policymakers to target efforts to increase resilience to climate change.

The development of highly effective malaria vaccines and improvement of drug- treatment protocols to boost antiparasitic immunity are critical for malaria elimination. However, the rapid establishment of parasite-specific immune regulatory networks following exposure to malaria parasites hampers these efforts. Here, we identified stimulator of interferon genes (STING) as a critical mediator of type I interferon production by [CD4.sup.+] T cells during blood-stage Plasmodium falciparum infection. The activation of STING in [CD4.sup.+] T cells by cyclic guanosine monophosphate- adenosine monophosphate (cGAMP) stimulated IFNB gene transcription, which promoted development of IL-10- and IFN- [gamma]-coproducing [CD4.sup.+] T (type I regulatory [Tr1]) cells. The critical role for type I IFN signaling for Tr1 cell development was confirmed in vivo using a preclinical malaria model. [CD4.sup.+] T cell sensitivity to STING phosphorylation was increased in healthy volunteers following P. falciparum infection, particularly in Tr1 cells. These findings identified STING expressed by [CD4.sup.+] T cells as an important mediator of type I IFN production and Tr1 cell development and activation during malaria., Introduction Malaria is a devastating human disease of global importance. It not only caused an estimated 247 million cases and 619,000 deaths in 2021, but also promoted poverty by imposing [...]

Background: The human peripheral nervous system embodies anatomical, physiologic, and diagnostic perplexities that remain unexplained. Yet in the course of human history, there are no mechanisms, such as computed tomography (CT) or radiography, by which to image the peripheral nervous system in vivo using a contrast agent that is identified by ionizing radiation, which would aid in surgical navigation, diagnostic radiology, and basic science thereof. Methods: A novel class of contrast was created by linking iodine to lidocaine. The radiodensity of 0.5% experimental contrast molecule was compared with a control of 1% lidocaine by placing 1.5-mL aliquots of each liquid into centrifuge tubes and performing micro–computed tomography (micro-CT) synchronously under identical settings. Physiologic binding to the sciatic nerve was evaluated by injecting 10 mg of the experimental contrast and 10 mg of the control into the contralateral sciatic nerve, and documenting loss of hindlimb function and recovery. In vivo visualization of the sciatic nerve was evaluated by injecting 10 mg of experimental contrast or control into either sciatic nerve and imaging the hindlimbs under identical conditions using micro-CT. Results: The mean Hounsfield unit of the contrast was 56.09 compared with −0.48 for control (116-fold increase, P =.0001). Hindlimb paresis revealed similar degree of paresis, baseline recovery, and time to recovery. In vivo enhancement between the contralateral sciatic nerves was similar. Conclusion: Iodinated lidocaine offers a viable mechanism for in vivo peripheral nerve imaging using CT; however, it requires modification to improve in vivo radiodensity. [ABSTRACT FROM AUTHOR]

Background: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing. Methodology: Results from 5 rounds over a 5-year period of the so far only longitudinal international Helminth External Molecular Quality Assessment Scheme (HEMQAS), coordinated by the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), were examined in order to (i) assess the diagnostic proficiency of laboratories in detecting helminths in stool and (ii) identify potential factors contributing to variations in performance. Outcome and conclusions: Thirty-six laboratories, from 18 countries and 5 continents, participated in HEMQAS. The overall diagnostic performances were satisfying, with remarkably low numbers (<2%) of false-positive results. False-negative results were more often reported for stool (15%) than for DNA (5%) samples. False-negative results varied largely between targets (the highest number (29%) for Trichuris trichiura). Twenty-five laboratories provided a sufficient number of results for a robust comparison between participating laboratories, which confirmed substantial inter-laboratory variability in quantitative NAAT results (Cq-values). This variability likely arises from differences in pre-treatment, DNA isolation and DNA-target amplification procedures. This study emphasizes the complexity of molecular diagnosis for STH and SCH, highlighting the critical role of proper stool preparation and DNA isolation methods. The results underscore the necessity for laboratory professionals and public health decision-makers to recognize these complexities and continuously undertake external quality assessment schemes to ensure accurate and reliable performance in molecular diagnosis. Author summary: Parasitic worms cause significant global health challenges, particularly in rural communities in low and middle-income countries. Laboratory tests that detect parasite DNA in human stool are increasingly being used for the diagnosis of parasitic worm infections. While parasite DNA detection can be an excellent diagnostic tool, its performance in clinical practice varies considerably, as demonstrated by previous research. To ensure the quality in diagnostic testing of these parasitic worms, it is important that laboratories evaluate the diagnostic performance of their DNA-based tests by participating in a so-called external quality assessment scheme (EQAS). This study, focusing on the first five-yearly rounds of the so far only longitudinal international EQAS to date, reveals that quantitative DNA detection results are not directly comparable across laboratories due to substantial inter-laboratory variability. This variability mainly stems from differences in pre-treatment and DNA isolation protocols, and to a lesser extent from differences in DNA target amplification procedures. Furthermore, the study underscores the complexity of molecular diagnosis for parasitic worms in clinical practice and the necessity for laboratories to engage in EQAs to guarantee the proper functioning of these diagnostic tests. [ABSTRACT FROM AUTHOR]

Although disturbance is considered a major driver of plant invasions across many systems, our understanding of the mechanisms by which disturbance mediates understorey invasions in natural forests is limited.We used a national natural forest inventory dataset spanning New Zealand's wide climatic and soil fertility gradients to disentangle disturbance‐mediated community characteristics driving abundance, species richness and functional composition of understorey plant invasions.Disturbance‐mediated declines in canopy tree abundance and increases in soil fertility and pH increased non‐native plant richness and cover relative to co‐occurring native plant assemblages. Cover of non‐native species also increased with proximity to anthropogenic land cover.Non‐native plant assemblages had higher community‐weighted mean (CWM) values for specific leaf area (SLA) but lower CWM values for height and woodiness relative to native assemblages irrespective of disturbance. However, greater nearby anthropogenic land cover drove increased woodiness in non‐native assemblages but decreased woodiness in co‐occurring native assemblages.Synthesis: Our study provides the first national‐scale evidence that canopy disturbance effects on soil properties increase both richness and abundance of non‐native plants in natural forest understories. We also revealed functional trait differences between native and non‐native assemblages (SLA in particular), which could alter fundamental forest ecosystem processes like litter decomposition and nutrient cycling. Finally, landscape‐scale anthropogenic impacts may exacerbate forest invasions by increasing non‐native abundance and favouring woody invaders, which may achieve dominance in future forest communities over the longer‐term. [ABSTRACT FROM AUTHOR]

Interactions between and within abiotic and biotic processes generate nonadditive density-dependent effects on species performance that can vary in strength or direction across environments. If ignored, nonadditivities can lead to inaccurate predictions of species responses to environmental and compositional changes. While there are increasing empirical efforts to test the constancy of pairwise biotic interactions along environmental and compositional gradients, few assess both simultaneously. Using a nationwide forest inventory that spans broad ambient temperature and moisture gradients throughout New Zealand, we address this gap by analyzing the diameter growth of six focal tree species as a function of neighbor densities and climate, as well as neighbor × climate and neighbor × neighbor statistical interactions. The most complex model featuring all interaction terms had the highest predictive accuracy. Compared with climate variables, biotic interactions typically had stronger effects on diameter growth, especially when subjected to nonadditivities from local climatic conditions and the density of intermediary species. Furthermore, statistically strong (or weak) nonadditivities could be biologically irrelevant (or significant) depending on whether a species pair typically interacted under average or more extreme conditions. Our study highlights the importance of considering both the statistical potential and the biological relevance of nonadditive biotic interactions when assessing species performance under global change. [ABSTRACT FROM AUTHOR]