The fluid movement of an arm requires multiple spatiotemporal parameters to be set independently. Recent studies have argued that arm movements are generated by the collective dynamics of neurons in ...motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independent components of the neural dynamics. Using a task where three male monkeys made a sequence of reaching movements to randomly placed targets, we show that the spatial and temporal parameters of arm movements are independently encoded in the lowdimensional trajectories of population activity in motor cortex: Each movement’s direction corresponds to a fixed neural trajectory through neural state space and its speed to how quickly that trajectory is traversed. Recurrent neural network models show this coding allows independent control over the spatial and temporal parameters of movement by separate network parameters. Our results support a key prediction of the dynamical systems view of motor cortex, but also argue that not all parameters of movement are defined by different trajectories of population activity Significance Statement From delicate strokes while drawing to ballistic swings while playing tennis, a skilled arm movement requires precise control of both its direction and speed. Motor cortex is thought to play a key role in controlling both, but it is unclear how they are jointly controlled. We show here that the population activity in motor cortex represents both the spatial and temporal properties of arm movements in the same low-dimensional signal. This representation was remarkably simple: the movement’s direction is represented by the trajectory that signal takes; the movement’s speed by how quickly the signal moves along its trajectory. Our network modelling shows this encoding allows an arm movement’s direction and speed to be simultaneously and independently controlled.
Anterior Cruciate Ligament Revision Reconstruction Miller, Mark D.; Kew, Michelle E.; Quinn, Courtney A.
Journal of the American Academy of Orthopaedic Surgeons,
09/2021, Volume:
29, Issue:
17
Journal Article
Peer reviewed
Revision anterior cruciate ligament (ACL) reconstruction is used in patients with recurrent instability after primary ACL reconstruction. Identifying the etiology of graft failure is critical to the ...success of revision reconstruction. The most common etiologies include technical errors, trauma, failure to recognize concomitant injuries, young age, incomplete rehabilitation, and hardware failure. Patients should undergo a complete history and physical examination with a specific focus on previous injury mechanism and surgical procedures. A revision ACL reconstruction is a technically demanding procedure, and the surgeon should be prepared to address bone tunnel osteolysis, concurrent meniscal, ligamentous, or cartilage lesions, and limb malalignment. Surgical techniques described in this article include both single-stage and two-stage reconstruction procedures. Rates of return to sport after a revision reconstruction are lower than after primary reconstruction. Future research should be focused on improving both single-stage and two-stage revision techniques, as well as concomitant procedures to address limb malalignment and associated injuries.
Background:
Anatomic reconstruction of the coracoclavicular (CC) ligaments has become a popular surgical treatment for high-grade acromioclavicular (AC) dislocations, but little has been reported ...about complications related to these newer surgical techniques.
Purpose:
We sought to review the complications related to several new techniques for the anatomic reconstruction of the CC ligaments for the treatment of AC separations.
Study Design:
Case series; Level of evidence, 4.
Methods:
We conducted a retrospective review of the operative treatment of AC separation utilizing anatomic reconstruction of the CC ligaments by reviewing the case logs of 3 fellowship-trained orthopaedic surgeons at a single academic sports medicine center for the past 5 years using appropriate current procedural terminology codes. The medical records and postoperative radiographs were assessed for complications.
Results:
Twenty-seven cases of anatomic reconstruction of the CC ligaments were reviewed. All patients had an autograft or allograft ligament reconstruction utilizing either a coracoid tunnel (10 cases) or a loop around the coracoid base (17 cases). Eight complications (80%) were noted in the coracoid tunnel group including 2 coracoid fractures (20%), 5 patients with some loss of reduction (more than 5-mm increased CC interval displacement on subsequent postoperative radiographs) (50%), and 1 patient with an intraoperative failure of the coracoid button fixation (10%). Six patients developed complications in the coracoid loop group (35%) including 3 clavicle fractures (18% within group, 11% overall), 1 patient with loss of reduction (6%), 1 patient with loss of reduction and an infection (6% within group, 4% overall), and 1 patient with adhesive capsulitis postoperatively (6% within group, 4% overall).
Conclusion:
Newer techniques for the anatomic reconstruction of the CC ligaments may have steep learning curves associated with complications such as coracoid and clavicle fractures. Loss of reduction continues to be associated with the operative treatment of high-grade AC separations. Further refinement of surgical technique and experience with the operative treatment of AC separation is warranted.
Full text
Available for:
FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Knowledge of the health impacts of environmental exposures (such as pollution disasters, poor air quality, water contamination, climate change) on children's health has dramatically increased in the ...past 40 years. The World Health Organization (WHO) estimated that 23% of all deaths worldwide were attributable to the environment, and 26% of deaths in children less than 5 years old could be prevented with removal of environmental risks factors. Yet, little has permeated medical education, leaving pediatric providers ill equipped to address these issues. To address this gap, members from the Pediatric Environmental Health Specialty Units, a United States nationwide network of academically affiliated experts who have created numerous environmental health educational materials and programs, have identified fifteen core environmental health (EH) competencies needed by health care providers to enable them to effectively address environmental health concerns. These competencies can serve as the foundation for the development and implementation of relevant educational programs. The core EH competencies are based upon these foundational elements: 1) Definition of "children's environmental health" that describes how environmental exposures (positive and negative) in early life influence the health and development in childhood and across the entire human life span 2) Children are not "little adults" and so have unique vulnerabilities to environmental hazards; 3) Environmental health inequities exist, causing some children to have a disproportionate amount of unhealthy exposures and consequently a greater risk of adverse effects; 4) Climate change will translate to numerous adverse health effects that will particularly affect children worldwide. In this article, the authors describe the core environmental health competencies and provide resources, online tools, strategies, and examples targeted to all levels of training and practice to better enable leaders and educators to bring this important content to the forefront.
The tammar wallaby (Notamacropus eugenii) is one of the most intensively studied of all macropodids and was the first Australasian marsupial to have its genome sequenced. However, comparatively ...little is known about genetic diversity and differentiation amongst the morphologically distinct allopatric populations of tammar wallabies found in Western (WA) and South Australia (SA). Here we compare autosomal and Y-linked microsatellite genotypes, as well as sequence data (~600 bp) from the mitochondrial DNA (mtDNA) control region (CR) in tammar wallabies from across its distribution. Levels of diversity at autosomal microsatellite loci were typically high in the WA mainland and Kangaroo Island (SA) populations (A = 8.9-10.6; He = 0.77-0.78) but significantly reduced in other endemic island populations (A = 3.8-4.1; He = 0.41-0.48). Autosomal and Y-linked microsatellite loci revealed a pattern of significant differentiation amongst populations, especially between SA and WA. The Kangaroo Island and introduced New Zealand population showed limited differentiation. Multiple divergent mtDNA CR haplotypes were identified within both SA and WA populations. The CR haplotypes of tammar wallabies from SA and WA show reciprocal monophyly and are highly divergent (14.5%), with levels of sequence divergence more typical of different species. Within WA tammar wallabies, island populations each have unique clusters of highly related CR haplotypes and each is most closely related to different WA mainland haplotypes. Y-linked microsatellite haplotypes show a similar pattern of divergence although levels of diversity are lower. In light of these differences, we suggest that two subspecies of tammar wallaby be recognized; Notamacropus eugenii eugenii in SA and N. eugenii derbianus in WA. The extensive neutral genetic diversity and inter-population differentiation identified within tammar wallabies should further increase the species value and usefulness as a model organism.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nineteen subjects have more than 18 months’ follow-up in a phase IIb tolerance protocol in HLA–mismatched recipients of living donor kidney plus facilitating cell enriched hematopoietic stem cell ...allografts (FCRx). Reduced intensity conditioning preceded a kidney allograft, followed the next day by FCRx. Twelve have achieved stable donor chimerism and have been successfully taken off immunosuppression (IS). We prospectively evaluated immune reconstitution and immunocompetence. Return of CD4 and CD8 T central and effector memory cell populations was rapid. T-cell receptor (TCR) Excision Circle analysis showed a significant proportion of chimeric cells produced were being produced de novo. The TCR repertoires posttransplant in chimeric subjects were nearly as diverse as pretransplant donors and recipients, and were comparable to subjects with transient chimerism who underwent autologous reconstitution. Subjects with persistent chimerism developed few serious infections when off IS. The majority of infectious complications occurred while subjects were still on conventional IS. BK viruria and viremia resolved after cessation of IS and no tissue-invasive cytomegalovirus infections occurred. Notably, although 2 of 4 transiently or nonchimeric subjects experienced recurrence of their underlying autoimmune disorders, none of the chimeric subjects have, suggesting that self-tolerance is induced in addition to tolerance to alloantigen. No persistently chimeric subject has developed donor-specific antibody, and renal function has remained within normal limits. Patients were successfully vaccinated per The American Society for Blood and Marrow Transplantation guidelines without loss of chimerism or rejection. Memory for hepatitis vaccination persisted after transplantation. Chimeric subjects generated immune responses to pneumococcal vaccine. These data suggest that immune reconstitution and immunocompetence are maintained in persistently chimeric subjects.
Abstract
Mutations in enhancers have been shown to often underlie natural variation but the evolved differences in enhancer activity can be difficult to identify in vivo. Threespine sticklebacks ...(Gasterosteus aculeatus) are a robust system for studying enhancer evolution due to abundant natural genetic variation, a diversity of evolved phenotypes between ancestral marine and derived freshwater forms, and the tractability of transgenic techniques. Previous work identified a series of polymorphisms within an intronic enhancer of the Bone morphogenetic protein 6 (Bmp6) gene that are associated with evolved tooth gain, a derived increase in freshwater tooth number that arises late in development. Here, we use a bicistronic reporter construct containing a genetic insulator and a pair of reciprocal two-color transgenic reporter lines to compare enhancer activity of marine and freshwater alleles of this enhancer. In older fish, the two alleles drive partially overlapping expression in both mesenchyme and epithelium of developing teeth, but the freshwater enhancer drives a reduced mesenchymal domain and a larger epithelial domain relative to the marine enhancer. In younger fish, these spatial shifts in enhancer activity are less pronounced. Comparing Bmp6 expression by in situ hybridization in developing teeth of marine and freshwater fish reveals similar evolved spatial shifts in gene expression. Together, these data support a model in which the polymorphisms within this enhancer underlie evolved tooth gain by shifting the spatial expression of Bmp6 during tooth development, and provide a general strategy to identify spatial differences in enhancer activity in vivo.
Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as ...hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.
Whole-genome sequencing (WGS) of maternal plasma cell-free DNA (cfDNA) can potentially evaluate all 24 chromosomes to identify abnormalities of the placenta, fetus, or pregnant woman. Current ...bioinformatics algorithms typically only report on chromosomes 21, 18, 13, X, and Y; sequencing results from other chromosomes may be masked. We hypothesized that by systematically analyzing WGS data from all chromosomes, we could identify rare autosomal trisomies (RATs) to improve understanding of feto-placental biology. We analyzed two independent cohorts from clinical laboratories, both of which used a similar quality control parameter, normalized chromosome denominator quality. The entire data set included 89,817 samples. Samples flagged for analysis and classified as abnormal were 328 of 72,932 (0.45%) and 71 of 16,885 (0.42%) in cohorts 1 and 2, respectively. Clinical outcome data were available for 57 of 71 (80%) of abnormal cases in cohort 2. Visual analysis of WGS data demonstrated RATs, copy number variants, and extensive genome-wide imbalances. Trisomies 7, 15, 16, and 22 were the most frequently observed RATs in both cohorts. Cytogenetic or pregnancy outcome data were available in 52 of 60 (87%) of cases with RATs in cohort 2. Cases with RATs detected were associated with miscarriage, true fetal mosaicism, and confirmed or suspected uniparental disomy. Comparing the trisomic fraction with the fetal fraction allowed estimation of possible mosaicism. Analysis and reporting of aneuploidies in all chromosomes can clarify cases in which cfDNA findings on selected "target" chromosomes (21, 18, and 13) are discordant with the fetal karyotype and may identify pregnancies at risk of miscarriage and other complications.
PDF
