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Alzheimer's disease, the most common form of dementia among older adults, slowly destroys memory and thinking skills. In recent years, scientists have made tremendous progress in understanding Alzheimer's disease, still, they do not yet fully understand what causes the disease. This article proposes a novel etiology for Alzheimer's disease. Our hypothesis developed from a review of nuclear medicine scans, in which the authors observed a significant increase in nasal turbinate vasodilation and blood pooling in patients with hypertension, sleep apnea, diabetes and/or obesity, all risk factors for Alzheimer's disease. The authors propose that nasal turbinate vasodilation and resultant blood pooling lead to the obstruction of normal nasal lymphatic clearance of cerebrospinal fluid and its waste products from the brain. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs alongside the well-established increased sympathetic activity of the cardiovascular system as seen in patients with hypertension. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of highly processed food associated with dysregulation of the glucose regulatory system. The authors' hypothesis offers a novel mechanism and a new paradigm for the etiology of Alzheimer's disease and helps explain the rapid worldwide rise in the disease and other dementias which are expected to double in the next 20 years. This new paradigm provides compelling evidence for the modulation of the parasympathetic nervous system as a novel treatment strategy for Alzheimer's disease and other degenerative brain diseases, specifically targeting nasal turbinate lymphatic flow. [ABSTRACT FROM AUTHOR]

The objective of this paper is to provide a history of the National Highway Traffic Safety Administration's (NHTSA's) extensive efforts of incorporating advanced airbag technology capability beyond that available in first-generation airbag systems into FMVSS No. 208. In the paper, NHTSA's actions and their collaborative efforts with automakers, automaker suppliers, insurance industry, academia, and other Federal agencies were reviewed, and the key efforts have been highlighted. Through their efforts, NHTSA developed its strategy by first undertaking near term actions and then undertaking the strategy for longer term actions. Rulemaking was undertaken in three steps. Then, as sufficient data became available, NHTSA documented the effectiveness of the rulemakings. The approach taken by NHTSA with the goal of preserving the safety benefits of the first-generation of frontal airbags while minimizing their danger to children and at-risk adults paved the way for the advanced airbags final rule and an interim final rule issued on May 12, 2000 (see Federal Register Notice 65 FR 30680). A follow-up final rule was issued on August 31, 2006, to change the test speed of the belted 5th percentile female dummy from 48 km/h to 56 km/h (30 mph to 35 mph). The final rule was updated on November 2, 2007, to permit manufacturers to earn advance credits for vehicles that are certified in compliance with the new higher speed requirement one year in advance of the regulatory requirements. NHTSA engagement in efforts with multiple partners toward identifying the safety issues, was an integral part of NHTSA's strategy in addressing the problem, arriving at immediate actions that NHTSA took, and detailing a comprehensive look at the longer-term approach required to resolve the safety issues. The approach taken by NHTSA paved the way for the advanced airbags final rule and an interim final rule issued on May 12, 2000 (Federal Register Notice 65 FR 30680). NHTSA had undertaken a successful collaboration of the Federal Government, the automobile industry, equipment suppliers, insurance companies, traffic safety advocates, law enforcement agencies from across the country, and the media to solve the airbag related safety issue. [ABSTRACT FROM AUTHOR]

The International Olympic Committee (IOC) has a complex and evolving legal status. While it is recognized as a non-governmental organization and registered as a Swiss association, it also has elements of international legal personality and enjoys privileges and immunities similar to those of an international organization. The IOC has been involved in legal cases, but its status as a Swiss association has been upheld. It operates independently and autonomously, negotiating directly with governments and international organizations. The IOC acknowledges and strives to comply with international human rights standards, although it is not formally bound by international human rights law. Overall, the IOC is gradually reclaiming the status it was intended to have and may eventually achieve full recognition as an international legal person. [Extracted from the article]

The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins. TMEM63s are mechanosensitive ion channels activated by hypo-osmolality. Here, the authors determine the cryo-EM structure of mouse TMEM63C confirming its predominant monomeric state and the significance of TM0-TM6 coupling in channel activity. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to determine the degree of progressive posthemorrhagic ventricular dilatation (PHVD) that is associated with a significant decrease in regional cerebral oxygen saturation (rScO 2) in premature infants at risk for periventricular–intraventricular hemorrhage (PIVH). Study Design Cranial ultrasound (US) and near-infrared spectroscopy (NIRS) measurements of rScO 2 were performed on inborn infants with birth weights less than 1,250 g on admission and at 1, 4, and 8 weeks of age. Infants with severe PIVH were studied weekly. A 1-hour average of rScO 2 was compared with the frontal–occipital horn ratio (FOHR) measured the same day. Generalized linear models were used to analyze the relationship between FOHR and rScO 2 , by severity of PIVH, and adjusted for gestational age. Cut-off points of 0.55 for FOHR and 45% for rScO 2 were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results The study cohort included 63 infants with normal US, 15 with grade-1 or -2 PIVH (mild group), and 21 with grade-3 or -4 PIVH (severe group). Increases in FOHR in the severe group were associated with decreases in rScO 2 at 1 week (p = 0.036), 4 weeks (p = 0.013), and 8 weeks of life (p = 0.001) compared with the normal and mild groups. Infants with FOHR greater than 0.55 were 92% more likely to have rScO 2 less than 45% when compared with infants with FOHR less than 0.55 (OR = 0.08, 95% CI: [0.04, 0.13], p < 0.001). Conclusion Progressive PHVD (FOHR > 0.55) is a strong predictor of compromised cerebral oxygenation. A combination of rScO 2 and FOHR measurements may aid in identifying infants with PHVD that would benefit from early intervention. Key Points Earlier intervention in PHVD may improve outcomes. PHVD is diagnosed with US measurements of ventricular size. FOHR > 0.55 is associated with decreased cerebral perfusion. [ABSTRACT FROM AUTHOR]

Effective rate‐adaptive pacing may be difficult in the presence of atrial fibrillation (AF), and is important during high‐intensity exercise. This case presents a 74‐year‐old elite cyclist with AF and a biventricular pacemaker after atrioventricular (AV) node ablation. He reported sudden breathlessness due to heart rate drops, caused by breaching the artefact threshold on the minute‐ventilation sensor. He was exchanged to a generator with an impedance‐derived contractility sensor (closed‐loop stimulation), resulting in resolution of symptoms, and no further rate drops. This is the first description of the utility of closed‐loop stimulation in high‐intensity exercise. [ABSTRACT FROM AUTHOR]

The article critically examines the Friedrich Nottebohm case, a landmark judgment on nationality, delving into its background and influence. It discusses the case's legacy, analyzing how it has been cited across various contexts, from the Court of Arbitration for Sport to the European Commission. It explores the critique surrounding Nottebohm and its potential misapplication.

This paper considers increasing global reliance on privately protected areas (PPAs) and associated nature-based tourism (NBT). A targeted literature review was guided by three research questions, which sought to understand how neoliberal concepts and dynamics manifest in private forms of conservation; how private forms of conservation have manifested in Chile; and, how Chileans' attitudes towards their government's neoliberal policies might affect their expectations of PPAs. The search strategy resulted in 284 resources. Three dimensions of neoliberal approaches to PPAs emerged from the data each highlighting specific vulnerabilities: a loss of the social embeddedness of nature; an imposition of global, capital dynamics; and conflicting discourses and assumptions. Results suggest that, in order to improve long-term support and integration of PPAs and NBT, greater attention needs to be given to social well-being outcomes (including equity and justice concerns), building of social capital, and the preservation of local identities and histories. Additionally, regional and PPA-specific land-use planning needs to incorporate greater public engagement, cross-jurisdictional coordination, and transparent and inclusive decision-making. [ABSTRACT FROM AUTHOR]

Following a recent judgment by the International Court of Justice (ICJ), a divergence has opened between the Court and the Committee on the Elimination of Racial Discrimination (CERD Committee) over whether the Convention on the Elimination of All Forms of Racial Discrimination (CERD) covers nationality-based discrimination. The ICJ held that the CERD does not, but the CERD Committee had previously held the opposite. The solution to this difference is to recognize that the CERD excludes discrimination between citizens and aliens, and, in this, the ICJ was correct. However, this discrimination is distinct from discrimination between foreign persons on the basis of their nationality, which is covered by the CERD. It is for this latter form of discrimination that the CERD Committee is correct. In essence, the ICJ and the CERD Committee are both partly wrong and partly correct, and by identifying this nuance between forms of nationality discrimination, we can reconcile the two views. [ABSTRACT FROM AUTHOR]

Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

In the most recent few years, state practice and opinio juris are increasingly converging to affirm that states must grant nationality to children born in their territory if they would otherwise be stateless. In prior scholarship, this author has argued that there is a customary international law norm requiring states to grant nationality in such cases. Certainly, UNHCR's #IBelong campaign is a significant part of this development, placing statelessness back on the international agenda, as well as encouraging states to adhere to the statelessness conventions, adopt birth registration and statelessness determination procedures and revise domestic law. Partly due to this campaign, states are increasingly adopting practice and domestic law that provides for nationality from birth for stateless children but are also increasingly stating their opinion that such an approach is desirable, necessary and morally compelling. In fact, it is effectively impossible to identify any state that claims it has the unfettered right to refuse to grant nationality to a stateless child born in its territory. This article will complete a brief survey of recent practice and expressions of opinion, mostly as documented by UNHCR as a part of the #IBelong Campaign to End Statelessness, to confirm that this norm continues to strengthen under customary international law. [ABSTRACT FROM AUTHOR]

Multiligament injury of the knee usually occurs as a result of high-energy trauma causing tibiofemoral dislocation. These are rare but potentially limb-threatening injuries, frequently involving nerve or arterial damage and often leading to severe complex instability. Management generally favours surgical reconstruction of the affected ligaments, with controversy regarding optimal treatment. We present a severe multiligament knee injury (Schenk classification KD-IV involving both cruciate and both collateral ligaments) in a competitive showjumper. A combined arthroscopic/open technique of single-stage surgical repair and suture augmentation was used, repairing all affected ligaments. The patient made an excellent recovery, returning to work after 12 weeks and riding after 22 weeks. After 5-year follow-up, she has regained her previous level of competition without subsequent injury. Multiligament repair with suture augmentation is a viable approach to the management of knee dislocation injuries. We propose that this could provide superior outcomes to traditional reconstruction techniques using autograft or synthetic reconstruction. [ABSTRACT FROM AUTHOR]

This essay examines the abbreviated fiction-writing career of an unlikely author, Central of Georgia Railway agricultural agent Jesse Frisbie Jackson. In the process, the essay explores the centrality of storytelling to the early twentieth-century United States, to farming and agricultural reform, and to the historical profession. [ABSTRACT FROM AUTHOR]

Objective: Complement activation is instrumental in the pathogenesis of Hypoxic-ischemic encephalopathy (HIE), a significant cause of neonatal mortality and disability worldwide. Therapeutic hypothermia (HT), the only available treatment for HIE, only modestly improves outcomes. Complement modulation as a therapeutic adjunct to HT has been considered, but is challenging due to the wide-ranging role of the complement system in neuroinflammation, homeostasis and neurogenesis in the developing brain. We sought to identify potential therapeutic targets by measuring the impact of treatment with HT on complement effector expression in neurons and glia in neonatal HIE, with particular emphasis on the interactions between microglia and C1q. Methods: The Vannucci model was used to induce HIE in term-equivalent rat pups. At P10-12, pups were randomly assigned to three different treatment groups: Sham (control), normothermia (NT), and hypothermia (HT) treatment. Local and systemic complement expression and neuronal apoptosis were measured by ELISA, TUNEL and immunofluorescence labeling, and differences compared between groups. Results: Treatment with HT is associated with decreased systemic and microglial expression of C1q, decreased systemic C5a levels, and decreased microglial and neuronal deposition of C3 and C9. The effect of HT on cytokines was variable with decreased expression of pro and anti-inflammatory effectors. HT treatment was associated with decreased C1q binding on cells undergoing apoptosis. Conclusion: Our data demonstrate the extreme complexity of the immune response in neonatal HIE. We propose modulation of downstream effectors C3a and C5a as a therapeutic adjunct to HT to enhance neuroprotection in the developing brain. [ABSTRACT FROM AUTHOR]

Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids. [ABSTRACT FROM AUTHOR]

Purpose: To develop and evaluate a volumetric modulated arc therapy (VMAT) machine parameter optimization (MPO) approach based on deep‐Q reinforcement learning (RL) capable of finding an optimal machine control policy using previous prostate cancer patient CT scans and contours, and applying the policy to new cases to rapidly produce deliverable VMAT plans in a simplified beam model. Methods: A convolutional deep‐Q network was employed to control the dose rate and multileaf collimator of a C‐arm linear accelerator model using the current dose distribution and machine parameter state as input. A Q‐value was defined as the discounted cumulative cost based on dose objectives, and experience‐replay RL was performed to determine a policy to minimize the Q‐value. A two‐dimensional network design was employed which optimized each opposing leaf pair independently while monitoring the corresponding dose plane blocked by those leaves. This RL approach was applied to CT and contours from 40 retrospective prostate cancer patients. The dataset was split into training (15 patients) and validation (5 patients) groups to optimize the network, and its performance was tested in an independent cohort of 20 patients by comparing RL‐based dose distributions to conformal arcs and clinical intensity modulated radiotherapy (IMRT) delivering a prescription dose of 78 Gy in 40 fractions. Results: Mean ± SD execution time of the RL VMAT optimization was 1.5 ± 0.2 s per slice. In the test cohort, mean ± SD (P‐value) planning target volume (PTV), bladder, and rectum dose were 80.5 ± 2.0 Gy (P < 0.001), 44.2 ± 14.6 Gy (P < 0.001), and 43.7 ± 11.1 Gy (P < 0.001) for RL VMAT compared to 81.6 ± 1.1 Gy, 51.6 ± 12.9 Gy, and 36.0 ± 12.3 Gy for clinical IMRT. Conclusions: RL was applied to VMAT MPO using clinical patient contours without independently optimized treatment plans for training and achieved comparable target and normal tissue dose to clinical plans despite the application of a relatively simple network design originally developed for video‐game control. These results suggest that extending a RL approach to a full three‐dimensional beam model could enable rapid artificial intelligence‐based optimization of deliverable treatment plans, reducing the time required for radiotherapy planning without requiring previous plans for training. [ABSTRACT FROM AUTHOR]

The article discusses the legal obligations and human rights violations allegedly committed by Great Britain due to its continuous use of the Five Techniques for interrogations despite its pledge to the European Court of Human Rights (ECtHR) to discontinue it. Also cited are the various probes on the alleged use of the methods by British forces in Iraq and Afghanistan in 2018, and why Great Britain's pledge is legally binding based on International Law Commission (ILC) guidelines.

Through a multi-layered, overlapping collection of international and regional treaties, one solution for child statelessness is emerging: the obligation of the birth state to grant nationality to otherwise stateless children. The 1961 Statelessness Convention imposes this obligation partly, but has limited adherence. The International Covenent on Civil and Political Rights provides for a right to a nationality, but does not expressly identify which state is responsible. In addition, treaties in Europe and Africa only cover the right implicitly and partially, though treaties in the Americas cover the right expressly. The interpetation of these disparate treaty obligations is now coalescing into an coherent obligation. In combination with the obligation to take all decisions in a child's best interests under the Convention on the Rights of the Child, we can now identify the birth state as the state responsible for ensuring that every child is born with a nationality. [ABSTRACT FROM AUTHOR]

Fredrika Bremer (1801–65) was a Swedish novelist and reformer primarily known for her role in advocating for women's voting and property rights in Sweden. This article analyzes her 1849–51 journey through North America and argues that she was also an important environmental figure who deserves renewed attention from environmental historians because of her embodied approach to environmental aesthetics, or what I call "aesthetic habitation." More broadly, Bremer's story suggests that environmental history needs an "aesthetic imperative" to go along with the more traditional moral and analytical imperatives of the field. [ABSTRACT FROM AUTHOR]

This article profiles the native bluestem grass broomsedge (Andropogon virginicus) and the role it has played in the history of the U.S. South. It describes how nineteenth-century agricultural reformers, early twentieth-century novelists, and late twentieth-century ecologists studied and used the grass as an indicator of the South's prospects for agricultural, economic, and cultural success. The article concludes by discussing what broomsedge might mean for the South's twenty-first-century future. [ABSTRACT FROM AUTHOR]

High-risk injection related behavior including use of non-sterile syringes is associated with negative health outcomes among people who inject drugs (PWID). Drug treatment programs have been reported to curb hepatitis C (HCV) transmission. This study aims to assess the role of drug treatment programs and knowledge of HCV status, and how they influence current injection-related risk. Data were collected in 2012 by the New Orleans arm of the CDC funded National HIV Behavioral Surveillance. Respondent driven sampling was used to recruit a sample of PWID. The analytic sample consisted of 473 participants. Univariate, bivariate, and linear regression analyses were performed. Findings indicated that history of drug treatment is associated with sterile syringe use among PWID. Further, knowledge of HCV status modifies the relationship between history of drug treatment and sterile syringe use in this sample. These findings highlight the importance of scaling up prevention efforts by expanding testing, counselling, and treatment for HCV among PWID who enter drug treatment facilities. [ABSTRACT FROM AUTHOR]

This submission challenges the presumption that UK nationals will lose EU citizenship following Brexit. Until now, the dominant narrative has been drawn from the law on treaties or international organizations, and this article adds the human rights perspective to Brexit. Firstly, EU citizenship can be assimilated to nationality. While EU citizenship is unique, the status protected under international law is a legal bond a person has with a political entity. This protection certainly covers nationality, and this paper argues it can be understood to also protect EU citizenship. Secondly, international law prohibits arbitrary withdrawal of this legal bond with a person. The UK does not have jurisdiction over EU citizenship, so it is doubtful the UK can terminate EU citizenship unilaterally. Even if the EU were to withdraw EU citizenship on its initiative, it would still constitute retroactive law, discrimination, and infringement of sovereignty. It is also disproportionate, because the loss of EU citizenship is not necessary for Brexit. When Greenland withdrew from the EU, its residents retained EU citizenship. For these reasons, the revocation of EU citizenship would be arbitrary. A distinction must be made between the membership of a state in the EU which can be terminated, and the direct legal bond formed between a person and the Union, which is far harder to revoke. On this basis, any UK national who has acquired EU citizenship prior to Brexit, should not be divested of it following Brexit. [ABSTRACT FROM AUTHOR]

Maps are often used as evidence in international relations, but their function can be much broader. In fact, their function can include proving facts, establishing legal relations and even creating new law. Maps can be used as evidence for both questions of law and questions of fact. Maps can prove the existence of a geographic feature but can also help determine what, if any, legal obligations might exist based on those geographic features. Maps themselves can be legal acts - the creation of a map itself can be a legal act, and legal obligations can flow from the features included in the map. This paper will consider the role of maps as evidence of facts, evidence of normativity, evidence of normative content, legal facts, elements of legal acts, and self-contained legal acts. [ABSTRACT FROM AUTHOR]

Hippocampus place cell discharge is temporally unreliable across seconds and days, and place fields are multimodal, suggesting an "ensemble cofiring" spatial coding hypothesis with manifold dynamics that does not require reliable spatial tuning, in contrast to hypotheses based on place field (spatial tuning) stability. We imaged mouse CA1 (cornu ammonis 1) ensembles in two environments across three weeks to evaluate these coding hypotheses. While place fields "remap," being more distinct between than within environments, coactivity relationships generally change less. Decoding location and environment from 1-s ensemble location-specific activity is effective and improves with experience. Decoding environment from cell-pair coactivity relationships is also effective and improves with experience, even after removing place tuning. Discriminating environments from 1-s ensemble coactivity relies crucially on the cells with the most anti-coactive cell-pair relationships because activity is internally organized on a low-dimensional manifold of non-linear coactivity relationships that intermittently reregisters to environments according to the anti-cofiring subpopulation activity. [Display omitted] • Hippocampal CA1 place fields change randomly across environments, known as remapping • Place field remapping only causes modest changes in short-timescale CA1 population cofiring • Environment-specific cofiring patterns are smooth trajectories on the CA1 neural manifold • ∼20% of CA1 cells with the most anti-cofiring discharge relationships discriminate environments Levy et al. find seconds-timescale hippocampus population discharge is relatively unchanged across environments despite place fields remapping to random locations. This population cofiring defines a CA1 manifold that distinctly registers to each environment by an environment-specific anti-cofiring subset of cells that mainly discharge when most other cells do not. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Purpose Sagittally reconstructed 3D ( SR3D) ultrasound imaging shows promise for improved needle localization for high-dose-rate prostate brachytherapy ( HDR- BT); however, needles must be manually segmented intraoperatively while the patient is anesthetized to create a treatment plan. The purpose of this article was to describe and validate an automatic needle segmentation algorithm designed for HDR- BT, specifically capable of simultaneously segmenting all needles in an HDR- BT implant using a single SR3D image with ~5 mm interneedle spacing. Materials and Methods The segmentation algorithm involves regularized feature point classification and line trajectory identification based on the randomized 3D Hough transform modified to handle multiple straight needles in a single image simultaneously. Needle tips are identified based on peaks in the derivative of the signal intensity profile along the needle trajectory. For algorithm validation, 12 prostate cancer patients underwent HDR- BT during which SR3D images were acquired with all needles in place. Needles present in each of the 12 images were segmented manually, providing a gold standard for comparison, and using the algorithm. Tip errors were assessed in terms of the 3D Euclidean distance between needle tips, and trajectory error was assessed in terms of 2D distance in the axial plane and angular deviation between trajectories. Results In total, 190 needles were investigated. Mean execution time of the algorithm was 11.0 s per patient, or 0.7 s per needle. The algorithm identified 82% and 85% of needle tips with 3D errors ≤3 mm and ≤5 mm, respectively, 91% of needle trajectories with 2D errors in the axial plane ≤3 mm, and 83% of needle trajectories with angular errors ≤3°. The largest tip error component was in the needle insertion direction. Conclusions Previous work has indicated HDR- BT needles may be manually segmented using SR3D images with insertion depth errors ≤3 mm and ≤5 mm for 83% and 92% of needles, respectively. The algorithm shows promise for reducing the time required for the segmentation of straight HDR- BT needles, and future work involves improving needle tip localization performance through improved image quality and modeling curvilinear trajectories. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD. In the current study, we locally delivered VEGF and ANG1 alone or in combination to dystrophic hind limb skeletal muscle. Using functional imaging, we found the combination treatment as well as ANG1 alone prevented decline in muscle perfusion whereas VEGF alone had no effect compared to controls. These findings were validated histologically as demonstrated by increased alpha-smooth muscle actin-positive vessels in muscles that received either VEGF+ANG1 or ANG1 alone compared to the sham group. We further show that ANG1 alone slows progression of fibrosis compared to either sham or VEGF treatment. The findings from this study shed new light on the functional effects of vascular therapy and suggest that ANG1 alone may be a candidate therapy in the treatment of DMD. [ABSTRACT FROM AUTHOR]

A 10-year-old boy struck a car bonnet following which his left shoulder got pinned under the wheel. No life-threatening injuries were identified. However, the patient sustained extensive abrasions to the back and the left shoulder, a closed deformity of the left clavicle and a swollen, but stable right knee. The patient was neurovascularly intact globally and all joints had a full range of motion. Plain radiographs suggested a possible greenstick fracture of the left clavicle, but also free gas within the left glenohumeral joint. Concern was raised of an unidentified open injury to the joint. CT was supportive of the finding of gas within the left glenohumeral joint, but ruled out the possible greenstick fracture as a spurious finding. There were no other injuries. The gas was within the left glenohumeral joint and was consistent with vacuum phenomenon. The injury was treated expectantly and the child made a full recovery. [ABSTRACT FROM AUTHOR]

During litigation on the international plane, states sometimes will issue assurances either to the other litigant or to the international court directly. This article explores how those assurances interact with applications for provisional measures. The practice of courts varies with regard to how to react to these assurances, though the usual approach is that assurances issued to another state or individual are generally non-binding, while assurances issued to the court directly are binding. At the same time, litigants can apply to the court for provisional measures to prevent actions that would disturb the dispute. When the assurances are considered non-binding, they are treated as questions of fact and can be assessed for credibility and reliability, as a part of the provisional measures analysis. But when the assurances are considered binding, they are treated as questions of law, and the undertaken legal obligation disposes of the request for a provisional measures order. This article will examine the practices of the International Court of Justice and the European Court of Human Rights on this issue, identifying where their practices diverge and converge, and recommending that the dual nature of assurances, as both factual and legal, be considered in assessing their value. [ABSTRACT FROM AUTHOR]

Pain is a major problem for Intensive Care Unit (ICU) patients. Despite numerous improvements it is estimated that as many as 70% of the patients experience moderateto- severe postoperative pain during their stay in the ICU. Effective pain management means not only decreasing pain intensity, but also reducing the opioids' side effects. Minimizing nausea, vomiting, urinary retention, and sedation may indeed facilitate patient recovery and it is likely to shorten the ICU and hospital stay. Adequate postoperative and post-trauma pain management is also crucial for the achievement of effective rehabilitation. Furthermore, recent studies suggest that effective acute pain management may be helpful in reducing the development of chronic pain. When used appropriately, and in combination with other treatment modalities, regional analgesia techniques (neuraxial and peripheral nerve blocks) have the potential to reduce or eliminate the physiological stress response to surgery and trauma, decreasing the possibility of surgical complications and improving the outcomes. Also they may reduce the total amount of opioid analgesics necessary to achieve adequate pain control and the development of potentially dangerous side effects. [ABSTRACT FROM AUTHOR]

This article will consider whether contemporary international law has evolved to a point where there is now an individual right to receive asylum opposable to the state’s right to expel. In the literature, it is commonly understood that no such right to receive asylum exists. Instead, where treaties might provide for a ‘right to asylum’, the usual interpretation is not that the person has a right to receive asylum but rather a right to apply for it. This article questions whether this conclusion is still correct in the light of contemporary developments in the law.There are a significant number of considerations pointing to a right to receive asylum. In the drafting of Universal Declaration of Human Rights and Refugee Convention, there was already considerable disagreement over whether there should be a right to receive asylum but in the end a more conservative wording was adopted. However, some subsequent human rights treaties following the UDHR have explicitly provided for the right to receive asylum. The practice of states has also evolved, partly under the influence of these treaty regimes. States are increasingly providing for a right to receive asylum in their domestic law and assimilating refugees to asylum seekers, often granting asylum as the automatic result of a positive refugee status determination. The bulk of these practices are converging into a widespread and consistent practice with strong opinio juris on point. These trends suggest a crystallizing customary international law right to receive asylum, albeit limited to refugees. [ABSTRACT FROM AUTHOR]