The Morphology and Evolution of the Primate Brachial Plexus

Primate evolutionary history is inexorably linked to the evolution of a broad array of locomotor adaptations that have facilitated the clade’s invasion of new niches. Researchers studying the evolution of primates and of their individual locomotor adaptations have traditionally relied on bony morphology – a practical choice given the virtual non-existence of any other type of tissue in the fossil record. However, this focus downplays the potential importance of the many other structures involved in locomotion, such as muscle, cartilage, and neural tissue, which may each be influenced by separate selective forces because of their different roles in facilitating movement. This dissertation is an investigation into the evolution of primate anatomy with an emphasis on the peripheral nervous system, particularly that of the brachial plexus, its intraspecific patterning, and its interactions with muscle in relation to changes in locomotion across clades. As the primate nervous system directs voluntary motor movement to the limbs, thereby facilitating locomotion, its morphology may be expected to vary with primate locomotor proclivities and/or limb anatomy. This prediction has not been explicitly tested. The anatomy of the peripheral nervous system was studied using a comparative approach both within 29 genera of primates and among non-primate clades via extensive primary dissection and a broad literature search in order to better understand its evolution. Data on spinal nerve level contributions, axon combination and branching morphology, nerve distribution pattern, and neural relationships with other soft tissues are detailed with photographs and standardized descriptions for 79 specimens and 123 individual plexuses. 99 characters generated from observations made during dissection were then analyzed using a parsimony-based phylogenetics approach to evaluate the evolutionary patterns presented by the brachial plexus in primates. The phylogenies generated with the brachial plexus characters did not perfectly mirror commonly accepted primate phylogenies, suggesting that while there is some evolutionary signal contained in the plexus, its morphology may also be influenced by forelimb function. As robust hypotheses exist regarding extant primate phylogenetic relationships and evolutionary histories, character evolution was mapped onto existing molecular trees to better understand how the individual structures that comprise the brachial plexus may evolve independently or in concert at different taxonomic levels. The rate of brachial plexus evolution in clades and leaf taxa was then assessed, demonstrating a marked heterogeneity in the structure both within and among clades. Taxa that have undergone recent locomotor shifts since divergence from their most recent common ancestor, and particularly those who exhibit some amount of suspensory behaviors, exhibit the highest rates of evolution observed here. Notably, several ape genera exhibit brachial plexus evolutionary rates significantly higher than the primate mean, running counter to the notion that hominoids have undergone an evolutionary slowdown relative to other primates. As the true unit of homology in the peripheral nervous system is a subject of ongoing debate, several levels of discussion are necessary to understand the variation in primates and their place in the broader spectrum of tetrapod diversity. Macroanatomy, microanatomy, development, and comparative anatomy are explored in a broad context to evaluate the evolutionary trends of the primate peripheral nervous system and are discussed in detail

Evaluating causes of error in landmark-based data collection using scanners

In this study, we assess the precision, accuracy, and repeatability of craniodental landmarks (Types I, II, and III, plus curves of semilandmarks) on a single macaque cranium digitally reconstructed with three different surface scanners and a microCT scanner. Nine researchers with varying degrees of osteological and geometric morphometric knowledge landmarked ten iterations of each scan (40 total) to test the effects of scan quality, researcher experience, and landmark type on levels of intra- and interobserver error. Two researchers additionally landmarked ten specimens from seven different macaque species using the same landmark protocol to test the effects of the previously listed variables relative to species-level morphological differences (i.e., observer variance versus real biological variance). Error rates within and among researchers by scan type were calculated to determine whether or not data collected by different individuals or on different digitally rendered crania are consistent enough to be used in a single dataset. Results indicate that scan type does not impact rate of intra- or interobserver error. Interobserver error is far greater than intraobserver error among all individuals, and is similar in variance to that found among different macaque species. Additionally, experience with osteology and morphometrics both positively contribute to precision in multiple landmarking sessions, even where less experienced researchers have been trained in point acquisition. Individual training increases precision (although not necessarily accuracy), and is highly recommended in any situation where multiple researchers will be collecting data for a single project

Frameless Image-Guided Radiosurgery for Trigeminal Neuralgia

Background: Frameless image-guided radiosurgery (IGRS) is a safe and effective noninvasive treatment for trigeminal neuralgia (TN). This study evaluates the use of frameless IGRS to treat patients with refractory TN. Methods: We reviewed the records of 20 patients diagnosed with TN who underwent frameless IGRS treatments between March 2012 and December 2013. Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. The initial setup uncertainty from simulation to treatment and the patient intrafraction uncertainty were measured. The median follow-up was 32 months. Results: All patients\u27 pain was BNI Grade IV or V before the frameless IGRS treatment. The mean intrafraction shift was 0.43 mm (0.28-0.76 mm), and the maximum intrafraction shift was 0.95 mm (0.53-1.99 mm). At last follow-up, 8 (40%) patients no longer required medications (BNI 1 or 2), 11 (55%) patients were pain free but required medication (BNI 3), and 1 (5%) patient had no pain relief (BNI 5). Patients who did not have prior surgery had a higher odds ratio for pain relief compared to patients who had prior surgery (14.9, P = 0.0408). Conclusions: Frameless IGRS provides comparable dosimetric and clinical outcomes to frame-based SRS in a noninvasive fashion for patients with medically refractory TN

The reconstructed cranium of Pierolapithecus and the evolution of the great ape face

Pierolapithecus catalaunicus (~12 million years ago, northeastern Spain) is key to understanding the mosaic nature of hominid (great ape and human) evolution. Notably, its skeleton indicates that an orthograde (upright) body plan preceded suspensory adaptations in hominid evolution. However, there is ongoing debate about this species, partly because the sole known cranium, preserving a nearly complete face, suffers from taphonomic damage. We 1) carried out a micro computerized tomography (CT) based virtual reconstruction of the Pierolapithecus cranium, 2) assessed its morphological affinities using a series of two-dimensional (2D) and three-dimensional (3D) morphometric analyses, and 3) modeled the evolution of key aspects of ape face form. The reconstruction clarifies many aspects of the facial morphology of Pierolapithecus. Our results indicate that it is most similar to great apes (fossil and extant) in overall face shape and size and is morphologically distinct from other Middle Miocene apes. Crown great apes can be distinguished from other taxa in several facial metrics (e.g., low midfacial prognathism, relatively tall faces) and only some of these features are found in Pierolapithecus, which is most consistent with a stem (basal) hominid position. The inferred morphology at all ancestral nodes within the hominoid (ape and human) tree is closer to great apes than to hylobatids (gibbons and siamangs), which are convergent with other smaller anthropoids. Our analyses support a hominid ancestor that was distinct from all extant and fossil hominids in overall facial shape and shared many features with Pierolapithecus. This reconstructed ancestral morphotype represents a testable hypothesis that can be reevaluated as new fossils are discovered.Fil: Pugh, Kelsey D.. City University of New York; Estados UnidosFil: Catalano, Santiago Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Pérez de los Ríos, Miriam. Universidad Complutense de Madrid. Facultad de Biología; EspañaFil: Fortuny, Josep. Institut Català de Paleontologia Miquel Crusafont.; EspañaFil: Shearer, Brian M.. New York Consortium in Evolutionary Primatology; Estados Unidos. New York University Grossman School of Medicine; Estados UnidosFil: Vecino Gazabón, Alessandra. American Museum of Natural History; Estados Unidos. New York Consortium in Evolutionary Primatology; Estados UnidosFil: Hammond, Ashley S.. American Museum of Natural History; Estados Unidos. New York Consortium in Evolutionary Primatology; Estados UnidosFil: Moyà Solà, Salvador. Institut Català de Paleontologia Miquel Crusafont.; España. Institució Catalana de Recerca i Estudis Avancats; España. Universitat Autònoma de Barcelona; EspañaFil: Alba, David M.. Institut Català de Paleontologia Miquel Crusafont.; EspañaFil: Almécija, Sergio. American Museum of Natural History; Estados Unidos. New York Consortium in Evolutionary Primatology; Estados Unidos. Institut Català de Paleontologia Miquel Crusafont; Españ

Establishing Consensus on Essential Resources for Musculoskeletal Trauma Care Worldwide: A Modified Delphi Study

BACKGROUND: Despite evidence that formalized trauma systems enhance patient functional outcomes and decrease mortality rates, there remains a lack of such systems globally. Critical to trauma systems are the equipment, materials, and supplies needed to support care, which vary in availability regionally. The purpose of the present study was to identify essential resources for musculoskeletal trauma care across diverse resource settings worldwide. METHODS: The modified Delphi method was utilized, with 3 rounds of electronic surveys. Respondents consisted of 1 surgeon with expertise in musculoskeletal trauma per country. Participants were identified with use of the AO Trauma, AO Alliance, Orthopaedic Trauma Association, and European Society for Trauma and Emergency Surgery networks. Respondents rated resources on a Likert scale from 1 (most important) to 9 (least important). The "most essential" resources were classified as those rated ≤2 by ≥75% of the sampled group. RESULTS: One hundred and three of 111 invited surgeons completed the first survey and were included throughout the subsequent rounds (representing a 93% response rate). Most participants were fellowship-trained (78%) trauma and orthopaedic surgeons (90%) practicing in an academic setting (62%), and 46% had >20 years of experience. Respondents represented low-income and lower-middle-income countries (LMICs; 35%), upper-middle income countries (UMICs; 30%), and high-income countries (HICs; 35%). The initial survey identified 308 unique resources for pre-hospital, in-hospital, and post-hospital phases of care, of which 71 resources achieved consensus as the most essential. There was a significant difference (p < 0.0167) in ratings between income groups for 16 resources, all of which were related to general trauma care rather than musculoskeletal injury management. CONCLUSIONS: There was agreement on a core list of essential musculoskeletal trauma care resources by respondents from LMICs, UMICs, and HICs. All significant differences in resource ratings were related to general trauma management. This study represents a first step toward establishing international consensus and underscores the need to prioritize resources that are locally available. The information can be used to develop effective guidelines and policies, create best-practice treatment standards, and advocate for necessary resources worldwide. CLINICAL RELEVANCE: This study utilized the Delphi method representing expert opinion; however, this work did not examine patient management and therefore does not have a clinical Level of Evidence

Implementation of Basal-Bolus Therapy in Type 2 Diabetes:A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch with an Insulin Pen

Background: Barriers to mealtime insulin include complexity, fear of injections, and lifestyle interference. This multicenter, randomized controlled trial evaluated efficacy, safety, and self-reported outcomes in adults with type 2 diabetes, inadequately controlled on basal insulin, initiating and managing mealtime insulin with a wearable patch versus an insulin pen. Methods: Adults with type 2 diabetes (n = 278, age: 59.2 +/- 8.9 years), were randomized to patch (n = 139) versus pen (n = 139) for 48 weeks, with crossover at week 44. Baseline insulin was divided 1:1 basal: bolus. Using a pattern-control logbook, subjects adjusted basal and bolus insulin weekly using fasting and premeal glucose targets. Results: Glycated hemoglobin (HbA1c) change (least squares mean +/- standard error) from baseline to week 24 (primary endpoint) improved (P \u3c 0.0001) in both arms, -1.7% +/- 0.1% and -1.6% +/- 0.1% for patch and pen (-18.6 +/- 1.1 and -17.5 +/- 1.1 mmol/mol), and was maintained at 44 weeks. The coefficient of variation of 7-point self-monitoring blood glucose decreased more (P = 0.02) from baseline to week 44 for patch versus pen. There were no differences in adverse events, including hypoglycemia (three severe episodes per arm), and changes in weight and insulin doses. Subject-reported treatment satisfaction, quality of life, experience ratings at week 24, and device preferences at week 48 significantly favored the patch. Most health care providers preferred patch for mealtime insulin. Conclusions: Bolus insulin delivered by patch and pen using an algorithm-based weekly insulin dose titration significantly improved HbA1c in adults with type 2 diabetes, with improved subject and health care provider experience and preference for the patch

Quality improvement in small office settings: an examination of successful practices

<p>Abstract</p> <p>Background</p> <p>Physicians in small to moderate primary care practices in the United States (U.S.) (<25 physicians) face unique challenges in implementing quality improvement (QI) initiatives, including limited resources, small staffs, and inadequate information technology systems 23,36. This qualitative study sought to identify and understand the characteristics and organizational cultures of physicians working in smaller practices who are actively engaged in measurement and quality improvement initiatives.</p> <p>Methods</p> <p>We undertook a qualitative study, based on semi-structured, open-ended interviews conducted with practices (N = 39) that used performance data to drive quality improvement activities.</p> <p>Results</p> <p>Physicians indicated that benefits to performing measurement and QI included greater practice efficiency, patient and staff retention, and higher staff and clinician satisfaction with practice. Internal facilitators included the designation of a practice champion, cooperation of other physicians and staff, and the involvement of practice leaders. Time constraints, cost of activities, problems with information management and or technology, lack of motivated staff, and a lack of financial incentives were commonly reported as barriers.</p> <p>Conclusion</p> <p>These findings shed light on how physicians engage in quality improvement activities, and may help raise awareness of and aid in the implementation of future initiatives in small practices more generally.</p

The Influence of International Law on the International Movement of Persons

Many migration theories identify ‘the law’ as a significant constraint on the international movement of persons. While this constraint often operates through national migration legislation, this study examines the influence of international law in shaping contemporary patterns in the international movement of persons at the macro level. The analysis begins with an examination of the long-established power of a State to regulate cross-border movement of persons as an inherent attribute of State sovereignty, together with the accepted limitations on a State’s power to control entry and exit. Yet, international law reaches well beyond the movement of people across borders. The development of international human rights law has been a key constraint on state action in the United Nations era by also regulating the treatment of migrants within a State’s borders. The study considers how international law has responded to current migration issues, including: protection of migrant women and children; suppression of smuggling and trafficking of people; labour migration; and environmental migration. As in other areas of international society, there has been a proliferation of institutions through which international migration law is made and enforced. The most prominent among them are the United Nations High Commissioner for Refugees (UNHCR) and the International Organization for Migration (IOM), but the establishment of other entities with overlapping mandates has given rise to calls for a new international migration regime based on streamlined institutional arrangements. The study concludes that international law is an imperfect framework for regulating the international movement of persons because it has developed in a piecemeal fashion over a long time to deal with issues of concern at particular points in human history. Yet, despite its shortfalls, international law and its associated institutions unquestionably play a most important role in constraining and channeling state authority over the international movement of persons

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways