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This tutorial presents the factor graph, a recently introduced estimation framework that is a generalization of the Kalman filter. An approach for constructing a factor graph, with its associated optimization problem and efficient sparse linear algebra formulation, is described. A comparison with Kalman filters is presented, together with examples of the generality of factor graphs. A brief survey of previous applications of factor graphs to navigation problems is also presented. Source code for the extended Kalman filter comparison and for generating the graphs in this paper is available at https://github.com/cntaylor/factorGraph2DsatelliteExample.

Context: In 2010, California experienced its largest pertussis epidemic in more than 60 years; a substantial burden of disease was noted in the 7- to 10-year-old age group despite high diphtheria, tetanus, and acellular pertussis vaccine (DTaP) coverage, indicating the possibility of waning protection.Objective: To evaluate the association between pertussis and receipt of 5 DTaP doses by time since fifth DTaP dose.Design, Setting, and Participants: Case-control evaluation conducted in 15 California counties. Cases (n = 682) were all suspected, probable, and confirmed pertussis cases among children aged 4 to 10 years reported from January through December 14, 2010; controls (n = 2016) were children in the same age group who received care from the clinicians reporting the cases. Three controls were selected per case. Vaccination histories were obtained from medical records and immunization registries.Main Outcome Measures: Primary outcomes were (1) odds ratios (ORs) for the association between pertussis and receipt of the 5-dose DTaP series and (2) ORs for the association between pertussis and time since completion (<12, 12-23, 24-35, 36-47, 48-59, or ≥60 months) of the 5-dose DTaP series. Logistic regression was used to calculate ORs, accounting for clustering by county and clinician, and vaccine effectiveness (VE) was estimated as (1 - OR) × 100%.Results: Among cases and controls, 53 (7.8%) and 19 (0.9%) had not received any pertussis-containing vaccines, respectively. Compared with controls, children with pertussis had a lower odds of having received all 5 doses of DTaP (OR, 0.11; 95% CI, 0.06-0.21 [estimated VE, 88.7%; 95% CI, 79.4%-93.8%]). When children were categorized by time since completion of the DTaP series, using an unvaccinated reference group, children with pertussis compared with controls were less likely to have received their fifth dose within the prior 12 months (19 [2.8%] vs 354 [17.6%], respectively; OR, 0.02; 95% CI, 0.01-0.04 [estimated VE, 98.1%; 95% CI, 96.1%-99.1%]). This association was evident with longer time since vaccination, with ORs increasing with time since the fifth dose. At 60 months or longer (n = 231 cases [33.9%] and n = 288 controls [14.3%]), the OR was 0.29 (95% CI, 0.15-0.54 [estimated VE, 71.2%; 95% CI, 45.8%-84.8%]). Accordingly, the estimated VE declined each year after receipt of the fifth dose of DTaP.Conclusion: Among children in 15 California counties, children with pertussis, compared with controls, had lower odds of having received the 5-dose DTaP series; as time since last DTaP dose increased, the odds increased, which is consistent with a progressive decrease in estimated vaccine effectiveness each year after the final dose of pertussis vaccine. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying cerebral angiogenesis have not been fully investigated. Using primary mouse brain endothelial cells (MBECs) and a capillary-like tube formation assay, we investigated whether the sonic hedgehog (Shh) signaling pathway is coupled with the plasminogen/plasmin system in mediating cerebral angiogenesis. We found that incubation of MBECs with recombinant human Shh (rhShh) substantially increased the tube formation in naïve MBECs. This was associated with increases in tissue plasminogen activator (tPA) activation and reduction of plasminogen activator inhibitor 1 (PAI-1). Blockage of the Shh pathway with cyclopamine abolished the induction of tube formation and the effect of rhShh on tPA and PAI-1. Addition of PAI-1 reduced rhShh-augmented tube formation. Genetic ablation of tPA in MBECs impaired tube formation and downregulated of vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). Addition of rhShh to tPA-/- MBECs only partially restored the tube formation and upregulated Ang1, but not VEGF, although rhShh increased VEGF and Ang1 expression on wild-type MBECs. Complete restoration of tube formation in tPA-/- MBECs was observed only when both exogenous Shh and tPA were added. The present study provides evidence that tPA and PAI-1 contribute to Shh-induced in vitro cerebral angiogenesis.

Abstract Background In malaria endemic areas, individuals are frequently asymptomatic and may be undetected by conventional microscopy or newer, rapid diagnostic tests. Molecular techniques allow a more accurate assessment of this asymptomatic parasite burden, the extent of which is important for malaria control. This study examines the relative prevalence of sub-microscopic level parasite carriage and clonal complexity of infections (multiplicity of infection) over a range of endemicities in a region of north-eastern Tanzania where altitude is an established proxy of malaria transmission. The PCR prevalence was then compared against other measures of transmission intensity collected in the same area. Methods This study used 1,121 blood samples collected from a previously conducted cross-sectional malario-metric survey during the short rainy season in 2001 from 13 villages (three at < 600 m, four at 600-1,200 m and six at > 1,200 m in altitude above sea level). Samples were analysed by PCR for carriage of parasites and multiplicity of infection. These data were compared with other measures of transmission intensity collected from the same area. Results Parasite prevalence was 34.7% by PCR and 13.6% by microscopy; a 2.5-fold difference in line with other recent observations. This fold difference was relatively consistent at the different altitude bands despite a marked decrease in parasite prevalence with altitude: < 600 m 70.9 vs 28.6, 600-1,200 m 35.5 vs 9.9, > 1,200 m 15.8 vs 5.9. The difference between parasite prevalence by PCR was 3.2 in individuals aged between 15 and 45 years (34.5 vs 10.9) compared with 2.5 in those aged 1-5 (34.0 vs 13.5) though this was not statistically significant. Multiplicity of infection (MOI) ranged from 1.2 to 3.7 and was positively associated with parasite prevalence assessed by both PCR and microscopy. There was no association of MOI and age. Village level PCR parasite prevalence was strongly correlated with altitude, sero-conversion rate and predicted entomological inoculation rate. Conclusions Asymptomatic, low density, multi-clone malaria infection was common in this study area. These infections are important as potential contributors to the infectious reservoir of parasites and need to be identified by control programmes especially in this era where malaria elimination is a focus. High throughput standardized PCR approaches are needed to identify individuals who are malaria carriers.

Abstract Background Transmission ratio distortion (TRD), defined as statistically significant deviation from expected 1:1 Mendelian ratios of allele inheritance, results in a reduction of the expected progeny of a given genotype. Since TRD is a common occurrence within interspecific crosses, a mouse interspecific backcross was used to genetically map regions showing TRD, and a developmental analysis was performed to identify the timing of allele loss. Results Three independent events of statistically significant deviation from the expected 50:50 Mendelian inheritance ratios were observed in an interspecific backcross between the Mus musculus A/J and the Mus spretus SPRET/EiJ inbred strains. At weaning M. musculus alleles are preferentially inherited on Chromosome (Chr) 7, while M. spretus alleles are preferentially inherited on Chrs 10 and 11. Furthermore, alleles on Chr 3 modify the TRD on Chr 11. All TRD loci detected at weaning were present in Mendelian ratios at mid-gestation and at birth. Conclusions Given that Mendelian ratios of inheritance are observed for Chr 7, 10 and 11 during development and at birth, the underlying causes for the interspecific TRD events are the differential post-natal survival of pups with specific genotypes. These results are consistent with the TRD mechanism being deviation from Mendelian inheritance rather than meiotic drive or segregation distortion.

Abstract Background Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE) is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. Results Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA) and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes) remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs) were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%). Conclusions Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes in the human term placenta. ZNF331 is imprinted in human term placenta and might be a new ubiquitously imprinted gene, part of a primate-specific locus. Demonstration of partial imprinting of PHACTR2 calls for re-evaluation of the allelic pattern of expression for the PHACTR2-PLAGL1 locus. ASE was common in human term placenta.

Abstract Background Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Results Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Conclusions Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.

Abstract Background HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women. Methods This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP) in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR. Results Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW). Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used. Conclusion Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a considerable impact on the burden of LBW in this population.

Abstract Background During malaria infection the Toll-like receptor 9 (TLR9) is activated through induction with plasmodium DNA or another malaria motif not yet identified. Although TLR9 activation by malaria parasites is well reported, the implication to the susceptibility to severe malaria is not clear. The aim of this study was to assess the contribution of genetic variation at TLR9 to severe malaria. Methods This study explores the contribution of TLR9 genetic variants to severe malaria using two approaches. First, an association study of four common single nucleotide polymorphisms was performed on both family- and population-based studies from Malawian and Gambian populations (n>6000 individual). Subsequently, it was assessed whether TLR9 expression is affected by cis-acting variants and if these variants could be mapped. For this work, an allele specific expression (ASE) assay on a panel of HapMap cell lines was carried out. Results No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs. Using an allele specific expression assay it was observed that TLR9 expression is affected by cis-acting variants, these results were replicated in a second experiment using biological replicates. Conclusion By using the largest cohorts analysed to date, as well as a standardized phenotype definition and study design, no association of TLR9 genetic variants with severe malaria was found. This analysis considered all common variants in the region, but it is remains possible that there are rare variants with association signals. This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals.

Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs), have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of pharmacovigilance systems in African countries deploying ACTs, additional guidance on adverse events monitoring in antimalarial clinical trials is needed, similar to the standardized recommendations available for assessment of drug efficacy.

Abstract Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP), artesunate + amodiaquine (AS+AQ), or artemether-lumefantrine (AL). Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years). At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7), or AS+AQ (anorexia: RR 2.10, 95% CI 1.04 – 4.23; weakness: RR 2.26, 95% CI 1.01 – 5.05). Extending the analysis to 42 days of follow-up had little impact on the findings. Conclusion This study confirms the safety and tolerability of AS+AQ and AL in Ugandan children, and suggests that AQ+SP is safe, but less well-tolerated, particularly in younger children. As newer antimalarial regimens are deployed, collecting data on their safety and tolerability will be essential. Trial registration Current Controlled Trials Identifier ISRCTN37517549

Abstract Background Presumptive treatment of malaria in febrile children is widely advocated in Africa. This may occur in the absence of diagnostic testing or even when diagnostic testing is performed but fails to detect malaria parasites. Such over-treatment of malaria has been tolerated in the era of inexpensive and safe monotherapy. However, with the introduction of new artemisinin-based combination therapy (ACT), presumptive treatment becomes economically and clinically less acceptable. Methods The risks and benefits of only treating children with microscopy confirmed malaria using a prospective cohort design were investigated. A representative sample of 601 children between one and 10 years of age were recruited from a census population in Kampala, Uganda and were followed for all of their health care needs in a study clinic. Standard microscopy was performed each time a child presented with a new episode of fever and antimalarial therapy given only if the blood smear was positive. Results Of 5,895 visits for new medical problems 40% were for febrile illnesses. Of the 2,359 episodes of new febrile illnesses, blood smears were initially reported as negative in 1,608 (68%) and no antimalarial therapy was given. Six of these initially negative smears were reported to be positive following quality control reading of all blood smears: four of these patients were subsequently diagnosed with uncomplicated malaria and two cleared their parasites without antimalarial treatment. Of the 1,602 new febrile illnesses in which the final blood smear reading was classified as negative, only 13 episodes (0.8%) were diagnosed with malaria in the subsequent 7 days. All 13 of these episodes of malaria were uncomplicated and were successfully treated. Conclusion In this urban setting, malaria was responsible for only 32% of febrile episodes. Withholding antimalarial therapy in febrile children with negative blood smears was safe and saved over 1,600 antimalarial treatments in 601 children over an 18-month period. In the era of expensive ACT, directing resources towards improving diagnostic and treatment practices may provide a cost-effective measure for promoting rational use of antimalarial therapy.

Abstract Background Studies of malaria in well-defined cohorts offer important data about the epidemiology of this complex disease, but few have been done in urban African populations. To generate a sampling frame for a longitudinal study of malaria incidence and treatment in Kampala, Uganda, a census, mapping and survey project was conducted. Methods All households in a geographically defined area were enumerated and mapped. Probability sampling was used to recruit a representative sample of children and collect baseline descriptive data for future longitudinal studies. Results 16,172 residents living in 4931 households in a densely-populated community (18,824 persons/km2) were enumerated. A total of 582 households were approached with at least one child less than 10 years of age in order to recruit 601 children living in 322 households. At enrollment, 19% were parasitaemic, 24% were anaemic, 43% used bednets, and 6% used insecticide-treated nets. Low G6PD activity (OR = 0.33, P = 0.009) and bednet use (OR = 0.64, P = 0.045) were associated with a decreased risk of parasitaemia. Increasing age (OR = 0.62 for each year, P < 0.001) and bednet use (OR = 0.58, P = 0.02) were associated with a decreased risk of anaemia Conclusion Detailed surveys of target populations in urban Africa can provide valuable descriptive data and provide a sampling frame for recruitment of representative cohorts for longitudinal studies. Plans to use a multi-disciplinary approach to improve the understanding of the distribution and determinants of malaria incidence and response to therapy in this population are discussed.

Abstract Background Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. Methods In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. Results Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations Conclusions These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

Background: Four-corner fusion (4CF) is a common treatment for midcarpal arthritis; however, alternatives including 2-corner fusion (2CF) and 3-corner fusion (3CF) have been described. Limited literature suggests 2CF and 3CF may improve range of motion but have higher complication rates. Our objective is to compare function and patient-reported outcomes following 4CF, 3CF, and 2CF at our institution., Methods: Adult patients undergoing 4CF, 3CF, and 2CF from 2011 to 2021 who attended at least one follow-up were included. Four-corner fusion patients were compared with those who underwent either 3CF or 2CF using staple fixation. Outcomes include nonunion rate, reoperation rate, progression to wrist fusion, range of motion, and patient-reported pain, satisfaction, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores., Results: A total of 58 patients met inclusion criteria. There were 49 4CF and 9 2CF or 3CF patients. Nonunion rates, progression to wrist fusion, and repeat surgery for any indication were not significantly different among groups. Range of motion (flexion-extension, radial-ulnar deviation) and grip strength at postoperative visits were not significantly different. Significantly more 4CF patients required bone grafting. Pain, overall satisfaction, and DASH scores were similar., Conclusions: Although prior studies suggest increased risk of nonunion and hardware migration after 2CF/3CF, we did not observe higher complication rates compared with 4CF. Range of motion, strength, and patient-reported outcomes were similar. While 4CF is traditionally the procedure of choice for midcarpal fusion, we found that when using a staple fixation technique, 2CF and 3CF have comparable clinical and patient-reported outcomes yet decrease the need for autologous bone grafting., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Adjunct nursing instructors (ANIs) are used to meet the needs of nursing education programs, but challenges of adjusting to unfamiliar academic settings often lead to poor job satisfaction and low retention of ANIs. The Adjunct Instructor Survey (Milliken & Jurgens, 2008) was used to query 25 ANIs regarding the importance and availability of support services pre-COVID-19 pandemic and post-pandemic. Mentoring was identified as most important pre- and post-pandemic, with a reported decrease in mentoring opportunities post-pandemic. Developing quality mentoring programs for ANIs needs to be a priority., (Copyright © 2024 InterVarsity Christian Fellowship.)

Purpose: Nerve transfers to restore or augment function after spinal cord injury is an expanding field. There is a paucity of information, however, on the use of nerve transfers for patients having undergone spine surgery. The incidence of neurologic deficit after spine surgery is rare but extremely debilitating. The purpose of this study was to describe the functional benefit after upper extremity nerve transfers in the setting of nerve injury after cervical spine surgery., Methods: A single-center retrospective review of all patients who underwent nerve transfers after cervical spine surgery was completed. Patient demographics, injury features, spine surgery procedure, nerve conduction and electromyography study results, time to referral to nerve surgeon, time to surgery, surgical technique and number of nerve transfers performed, complications, postoperative muscle testing, and subjective outcomes were reviewed., Results: Fourteen nerve transfers were performed in 6 patients after cervical spine surgery. Nerve transfer procedures consisted of a transfer between a median nerve branch of flexor digitorum superficialis into a biceps nerve branch, an ulnar nerve branch of flexor carpi ulnaris into a brachialis nerve branch, a radial nerve branch of triceps muscle into the axillary nerve, and the anterior interosseous nerve into the ulnar motor nerve. Average patient age was 55 years; all patients were male and underwent surgery on their left upper extremity. Average referral time was 7 months, average time to nerve transfer was 9 months, and average follow-up was 21 months. Average preoperative muscle grading was 0.9 of 5, and average postoperative muscle grading was 4.1 of 5 ( P < 0.00001)., Conclusions: Upper extremity peripheral nerve transfers can significantly help patients regain muscle function from deficits secondary to cervical spine procedures. The morbidity of the nerve transfers is minimal with measurable improvements in muscle function., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Family accommodation, or changes in parental behavior aimed at avoiding or alleviating child anxiety-related distress, contributes to the severity of anxiety symptoms, and is most strongly associated with separation anxiety. This study examined whether child attachment security, characterized as the degree to which children perceive their parents to be reliable, available, and communicative, moderates the association between family accommodation and separation anxiety symptoms, and whether this moderation is specific to separation anxiety among other anxiety symptoms. In a sample of clinically anxious children (N = 243, 6-12 years), family accommodation was significantly positively associated with separation anxiety symptoms across levels of attachment security. Family accommodation was more strongly associated with parent-reported separation anxiety symptoms in children with lower attachment security compared with those with higher attachment security. No significant moderation effect emerged for other anxiety symptoms. Findings enhance understanding of the role of attachment within family accommodation of child anxiety., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Care provided by Bachelor of Science in Nursing (BSN)-prepared Registered Nurses (RNs) has been shown to lead to more positive patient outcomes compared to care provided by non-BSN-prepared RNs. A Fall 2021 study explored barriers of requiring a BSN degree of staff nurses from the perspective of hospital and long-term care facility nurse leaders in Tennessee (N = 89), strategies to increase the number of nurses with BSNs, and association between leadership goals and the number of BSN-prepared nurses in the facilities. Seven barriers to requiring the BSN and nine strategies to increase BSNs were identified. Significant association was found between having plans to increase the number of BSN nurses and the percentage of nurses in the facility with BSN degrees., (Copyright © 2024 InterVarsity Christian Fellowship.)

Tardigrades, commonly known as 'waterbears', are eight-legged microscopic invertebrates renowned for their ability to withstand extreme stressors, including high osmotic pressure, freezing temperatures, and complete desiccation. Limb retraction and substantial decreases to their internal water stores results in the tun state, greatly increasing their ability to survive. Emergence from the tun state and/or activity regain follows stress removal, where resumption of life cycle occurs as if stasis never occurred. However, the mechanism(s) through which tardigrades initiate tun formation is yet to be uncovered. Herein, we use chemobiosis to demonstrate that tardigrade tun formation is mediated by reactive oxygen species (ROS). We further reveal that tuns are dependent on reversible cysteine oxidation, and that this reversible cysteine oxidation is facilitated by the release of intracellular reactive oxygen species (ROS). We provide the first empirical evidence of chemobiosis and map the initiation and survival of tardigrades via osmobiosis, chemobiosis, and cryobiosis. In vivo electron paramagnetic spectrometry suggests an intracellular release of reactive oxygen species following stress induction; when this release is quenched through the application of exogenous antioxidants, the tardigrades can no longer survive osmotic stress. Together, this work suggests a conserved dependence of reversible cysteine oxidation across distinct tardigrade cryptobioses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Smythers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Family accommodation, or changes in parental behavior aimed at avoiding or alleviating child anxiety-related distress, contributes to the severity of anxiety symptoms, and is most strongly associated with separation anxiety symptoms. This study examined whether child attachment security, characterized as the degree to which children perceive their parents to be reliable, available, and communicative, moderates the association between family accommodation and separation anxiety symptoms, and whether this moderator is specific to separation anxiety among other anxiety symptoms. In a sample of clinically anxious youth ( N = 243, 6-12 yrs), family accommodation was significantly positively associated with separation anxiety symptoms across levels of attachment security. Family accommodation was more strongly associated with separation anxiety symptoms in children with lower attachment security compared with those with higher attachment security. No significant moderation effect emerged for other anxiety symptoms. Findings enhance understanding of the role of attachment within family accommodation of child anxiety., Competing Interests: Additional Declarations: No competing interests reported.

Competing Interests: The author has no conflict of interest to declare.

Introduction: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma. Malignant peripheral nerve sheath tumors are aggressive tumors with high rates of local recurrence and metastasis. The prognosis is poor with 5-year survival rates of 15% to 50%. Unfortunately, given the rarity of these tumors, it is not clear how to best manage these patients. The purposes of this study were (1) to discuss our experience with MPNST and particularly our difficulties with diagnosis and management, and (2) to review the literature., Materials and Methods: We report on all tumors of the brachial plexus excised between 2013 and 2019. We report 3 cases of MPNST, their treatment, and their outcomes., Results: Thirteen patients underwent surgical excision of an intrinsic brachial plexus mass. Three of these patients (2 male, 1 female; average age, 36 years) were diagnosed with an MPNST. Two patients with an MPNST had neurofibromatosis type 1. All patients with an MPNST had a tumor >8 cm, motor and sensory deficits, and pain. All 3 patients with MPNST underwent a magnetic resonance imaging (MRI) before diagnosis. The average time from initial symptom onset to MRI was 12.3 months. Only 1 of the MRIs suggested a malignant tumor, with no MRI identifying an MPNST. One patient underwent an excisional biopsy, and 2 had incisional biopsies. Because of the lack of diagnosis preoperatively, all patients had positive margins given the limited extent of surgery. Returning for excision in an attempt to achieve negative margins in a large oncologically contaminated field was not possible because defining the boundaries of the initial surgical field was unachievable; therefore, the initial surgery was their definitive surgical management. All patients were referred to oncology and received radiation therapy., Conclusions: Malignant peripheral nerve sheath tumors must be suspected in enlarging masses (>5 cm) with the constellation of pain, motor, and sensory deficits. Computed tomography- or ultrasound-guided core needle biopsy under brachial plexus block or sedation is required for definitive diagnosis to allow for a comprehensive approach to the patient's tumor with a higher likelihood of disease-free survival., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Proximal interphalangeal joint (PIPJ) fracture dislocations are complex injuries that can result in persistent pain, stiffness, and angulation. Hemihamate arthroplasty (HHA) can be used to reconstruct the base of the middle phalanx in cases of unstable PIPJ fracture dislocations. Despite previous case series describing good outcomes with HHA, it has not gained widespread use. The purpose of this study is to describe our straightforward, reproducible technique and to demonstrate the benefit in motion after the procedure in chronic unstable PIPJ fracture dislocations., Methods: All patients with chronic, unstable PIPJ fracture dislocations requiring joint resurfacing of greater than 40% of the base of the middle phalanx treated with HHA were retrospectively reviewed. Patient demographics, injury features, surgical technique, preoperative and postoperative PIPJ range of motion and arc of motion, time to surgery, and complications were reviewed. Any fracture amenable to fixation or cases with radiographic evidence of arthritis or injury to the head of the proximal phalanx were excluded., Results: Eleven cases were reviewed. The mean patient age was 35 years. The mean time from injury to surgery was 6 months. The mean joint surface involved was 64%. The mean PIPJ arc of motion was 17 degrees preoperatively and 63 degrees postoperatively. The mean bone block size required was 8 × 8 × 8 mm. The mean follow-up was 26 months. Postoperative pain at the PIPJ on the visual analog scale was 0.4 (scale of 0 to 10). Complications included 2 patients requiring tenolysis., Conclusions: Despite the lack of a perfect geometric recreation of the base of the middle phalanx with the hamate, patients recover acceptable PIPJ motion and have minimal pain. Hemihamate arthroplasty is a good option for any patient with minimal motion of their PIPJ and a chronic, unstable fracture dislocation., Competing Interests: Conflicts of interests and sources of funding: None of the above authors have a conflict of interest to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A femoral nerve injury may result in cutaneous sensory disturbances of the anteromedial thigh and complete paralysis of the quadriceps femoris muscles resulting in an inability to extend the knee. The traditional mainstay of treatment for femoral neuropathy is early physiotherapy, knee support devices, and pain control. Case reports have used the anterior division of the obturator nerve as a donor nerve to innervate the quadriceps femoris muscles; however, a second nerve transfer or nerve grafting is often required for improved outcomes. We suggest a novel technique of combining an innervated, pedicled gracilis transfer with an adductor longus to rectus femoris nerve transfer to restore the strength and stability of the quadriceps muscles., Methods: This is a case series describing the use of a pedicled gracilis muscle transposed into the rectus femoris position with a concomitant nerve transfer from the adductor longus nerve branch into the rectus femoris nerve branch to restore quadriceps function after iatrogenic injury (hip arthroplasty) and trauma (gunshot wound)., Results: With electrodiagnostic confirmation of severe denervation of the quadriceps muscles and no evidence of elicitable motor units, 2 patients (average age, 47 years) underwent a quadriceps muscle reconstruction with a pedicled, innervated gracilis muscle and an adductor longus to recuts femoris nerve transfer. At 1 year follow-up, the patients achieved 4.5/5 British Medical Research Council full knee extension, a stable knee, and the ability to ambulate without an assistive aid., Conclusions: The required amount of quadriceps strength necessary to maintain quality of life has not been accurately established. In the case of femoral neuropathy, we assumed that a nerve transfer alone and a gracilis muscle transfer alone would not provide enough stability and strength to restore quadriceps function. We believe that the restoration of the quadriceps function after femoral nerve injury can be achieved by combining an innervated, pedicled gracilis transfer with an adductor longus to rectus femoris nerve transfer with low morbidity and no donor defects., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Parsonage Turner syndrome (PTS) is the development of severe, spontaneous pain with subsequent nerve palsy. Unfortunately, many patients never achieve full functional recovery, and many have chronic pain. The use of nerve transfers in PTS has not been reported in the literature. We present 4 cases of PTS treated surgically with primary nerve transfer and neurolysis of the affected nerve following the absence of clinical and electrodiagnostic recovery at 5 months from onset. In addition, we present a cadaver dissection demonstrating an interfascicular dissection of the anterior interosseous nerve (AIN) into its components to enable a fascicular transfer in partial AIN neuropathy. Two patients with complete axillary neuropathy underwent a neurorrhaphy between the nerve branch to the lateral head of the triceps and the anterior/middle deltoid nerve branch of the axillary nerve. Two patients with partial AIN neuropathy involving the FDP to the index finger (FDP2) underwent a neurorrhaphy between an extensor carpi radialis brevis nerve branch and the FDP2 nerve branch. All patients had neurolysis of the affected nerves. All subjects recovered at least M4 motor strength. The cadaver dissection demonstrates 3 separate nerve fascicles of the AIN into FPL, FDP2, and pronator quadratus that can be individually selected for reinnervation with a fascicular nerve transfer. Functional recovery for patients with PTS with neurolysis alone is variable. Surgical treatment with neurolysis and a nerve transfer to improve functional recovery when no recovery is seen by 5 months is an option., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transfer of the anterior interosseous nerve (AIN) into the ulnar motor branch improves intrinsic hand function in patients with high ulnar nerve injuries. We report our outcomes of this nerve transfer and hypothesize that any improvement in intrinsic hand function is beneficial to patients. Methods: A retrospective review of all AIN-to-ulnar motor nerve transfers, including both supercharged end-to-side (SETS) and end-to-end (ETE) transfers, from 2011 to 2018 performed by 2 surgeons was conducted. All adult patients who underwent this nerve transfer for any reason with greater than 6 months' follow-up and completed charts were included. Primary outcome measures were motor function using the British Medical Research Council (BMRC) grading system and subjective satisfaction with surgery using a visual analog scale. Secondary outcome measures included complications and donor site deficits. Results: Of the 57 patients who underwent nerve transfer, 32 patients met the inclusion criteria. The average follow-up and average time to surgery were 12 and 15.6 months, respectively. The overall average BMRC score was 2.9/5, with a trend toward better recovery in patients who received earlier surgery (<12 months = BMRC 3.7, ≥12 months = BMRC 2.2; P < .01). Patients with an SETS transfer had better results that those with an ETE transfer (SETS = 3.2, ETE = 2.6). There were no donor deficits after operation. One patient developed complex regional pain syndrome. Conclusions: Patients with earlier surgery and an in-continuity nerve (receiving an SETS transfer) showed improved recovery with a higher BMRC grade compared with those who underwent later surgery. Any improvements in intrinsic hand function would be beneficial to patients.

As of March 2021, three COVID-19 vaccines had been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic COVID-19 cases among vaccinated people (vaccine breakthrough infections) based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 199,000 symptomatic vaccine breakthrough infections (95% CI: ~183,000-214,000 cases) occurred in the United States during January-July 2021 among >156 million fully vaccinated people. With high SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake., Competing Interests: The authors have declared that no competing interests exist.

Background: This study brings a human-centered design (HCD) perspective to understanding the patient experience when using noninvasive ventilation (NIV) with the goal of creating better strategies to improve NIV comfort and tolerance., Methods: Using an HCD motivational approach, we created a semi-structured interview to uncover the patients' journey while being treated with NIV. We interviewed 16 patients with chronic obstructive pulmonary disease (COPD) treated with NIV while hospitalized. Patients' experiences were captured in a stepwise narrative creating a journey map as a framework describing the overall experience and highlighting the key processes, tensions, and flows. We broke the journey into phases, steps, emotions, and themes to get a clear picture of the overall experience levers for patients., Results: The following themes promoted NIV tolerance: trust in the providers, the favorable impression of the facility and staff, understanding why the mask was needed, how NIV works and how long it will be needed, immediate relief of the threatening suffocating sensation, familiarity with similar treatments, use of meditation and mindfulness, and the realization that treatment was useful. The following themes deterred NIV tolerance: physical and psychological discomfort with the mask, impaired control, feeling of loss of control, and being misinformed., Conclusions: Understanding the reality of patients with COPD treated with NIV will help refine strategies that can improve their experience and tolerance with NIV. Future research should test ideas with the best potential and generate prototypes and design iterations to be tested with patients., (JCOPDF © 2022.)