622 research outputs found
The Language of Compromise in International Agreements
To reach agreement, international negotiators often compromise by introducing flexibility in language: they make controversial provisions vague, or add options and caveats. Does flexibility in agreement language influence subsequent state behavior? If so, do states follow both firm and flexible language somewhat, as negotiators hope? Or do governments respond strategically, increasing their energies on firmly specified tasks, and reducing their efforts on flexibly specified ones? Testing theories about agreement language is difficult, because states often reserve flexible language for controversial provisions. To make causal claims, we study an unusually drafted agreement, in which states had almost no opportunity to dilute agreement language. We examine the influence of the 1991 Paris Principles on the Design of National Human Rights Institutions (NHRIs), using an original dataset of 22 institutional safeguards of NHRIs in 107 countries, and case studies. We find that variations in agreement language can have large effects on state behavior, even when the entire agreement is non-binding. Both democracies and authoritarian states followed the Principles’ firm terms closely. However, authoritarian states either ignored or reduced their efforts on flexibly specified tasks. If flexibly specifying a task is no different from omitting it altogether, as our data suggest, the costs of compromise are much greater than previously believed
Private Sector and Climate Change A Case Study of Carbon-Based Governance
Global greenhouse gas emissions are the main contributor to anthropocentrically-induced climate change and have risen 41% since 1990. We are still yet to reach peak emissions. A large share of those emissions result from private sector activity. At the same time, the private sector possesses major resources which should be harnessed to scale up funding and emissions reduction technologies to benefit the 3 climate. Since the Paris Climate Agreement in 2015, there has been an upsurge in private sector activity on climate change, especially in the corporate sector. Researchers have suggested that this groundswell of private sector activity especially in reduction of carbon emissions holds out the promise of plugging conspicuous public governance gaps. But while this surge in private action since the Paris Climate Agreement is to be encouraged, and indeed has been formally welcomed by global public climate governance actors under the UNFCCC, the measurable success of private, public-private and “hybrid” climate governance arrangements on reducing emissions remains unclear. Through an in depth empirical investigation of the actors and initiatives that play a key role in this emerging domain of bottom-up climate change governance, this study finds that, despite a groundswell in private activity, zones of fragmentation among a multiplicity of private actors, initiatives and standards is stymying progress: while key actors are increasingly networked, key metrics remain severely fragmented; while substantial resources have been dedicated to governing carbon emissions, greenhouse gas emissions keep rising. These observations are demonstrated through an empirical analysis of the “carbon-based” governance regime, which we define as the governance of climate change through a unitary focus on carbon measurement, disclosure, and verification. So far, the ultimate goal of carbon-based governance to reduce emissions is far from being realized. Whether this regime can be repurposed to fulfil this crucial function remains an open question
What Works in Human Rights Institutions?
Since 1993, the United Nations has promoted national human rights institutions (NHRIs); these have spread to almost 120 countries. We assess what makes NHRIs effective, using quantitative and qualitative methods. We find that formal institutional safeguards contribute greatly to NHRI efficacy even in authoritarian and transition regimes. Complaint-handling mandates are particularly useful because they help NHRIs build broad bases of support. Our findings show how international organizations can wield great influence with soft tools such as recommendations and peer-review mechanisms
Staffordshire Bull Terriers in the UK: their disorder predispositions and protections
Abstract: Background: The Staffordshire Bull Terrier is a popular dog breed in the UK but there is limited reliable evidence on disorder predispositions and protections within the breed. Using anonymised veterinary clinical data from the VetCompass™ Programme, this study aimed to identify common disorders with predisposition and protection in the Staffordshire Bull Terrier. The study hypothesised that Staffordshire Bull Terriers would have higher odds of aggression compared with non-Staffordshire Bull Terriers. Results: The clinical records of a random sample of dogs of all types were reviewed to extract the most definitive diagnoses for all disorders existing during 2016. A combined list from the 30 most common disorders in Staffordshire Bull Terriers and the 30 most common disorders in non-Staffordshire Bull Terriers was generated. Multivariable logistic regression was used to report the odds of each of these disorders in 1304 (5.8%) Staffordshire Bull Terriers compared with 21,029 (94.2%) non-Staffordshire Bull Terriers. After accounting for confounding, Staffordshire Bull Terriers had significantly increased odds of 4/36 (11.1%) disorders compared to non-Staffordshire Bull Terriers with highest odds for seizure disorder (OR 2.06; 95% CI 1.24 to 3.40; p = 0.005). Conversely, Staffordshire Bull Terriers had reduced odds of 5/36 (13.9%) disorders, with lowest odds for patellar luxation (OR 0.15; 95% CI 0.04 to 0.61; p = 0.008). There was no significant difference in the odds of aggression between Staffordshire Bull Terriers compared with non-Staffordshire Bull Terriers (OR 1.09; 95% CI 0.75 to 1.58; p = 0.644). Conclusions: This study provides a reliable evidence base of breed-specific disorder predispositions and protections that can be used by breeders to optimise breeding decisions. The findings can assist prospective owners of Staffordshire Bull Terriers to make informed decisions when acquiring a dog. From the relative number of predispositions to protections identified, there is no evidence that Staffordshire Bull Terriers have higher overall health problems than non-Staffordshire Bull Terriers
Risk factors for unilateral cranial cruciate ligament rupture diagnosis and for clinical management in dogs under primary veterinary care in the UK
This study aimed to evaluate demographic risk factors associated with unilateral cranial cruciate ligament (CCL) rupture diagnosis and to explore demographic and clinical risk factors associated with management of unilateral CCL rupture in dogs under primary veterinary care in the UK. A retrospective cohort study design was used. Clinical records were automatically searched and manually verified for incident cases of unilateral CCL rupture during 2019 and additional clinical management information extracted. Multivariable logistic regression modelling was used to evaluate associations between risk factors and: (1) CCL rupture diagnosis; and (2) clinical management (surgical or non-surgical). The analysis included 1000 unilateral CCL rupture cases and a random selection of 500,000 non-cases. After accounting for confounding factors, dogs aged 6 to < 9 years, male neutered and female neutered dogs, insured dogs, and Rottweiler, Bichon Frise, and West Highland White terrier breeds, in particular, had increased odds of unilateral CCL rupture diagnosis. Insured dogs and dogs ≥ 20 kg had increased odds of surgical management, while dogs ≥ 9 years and dogs with one non-orthopaedic comorbidity at diagnosis with CCL rupture had reduced odds. These findings inform identification of at-risk dogs, with Rottweilers and Bichon Frise particularly predisposed. Additionally, they contribute to a greater understanding of the clinical rationales used in primary-care veterinary practices to decide between surgical or non-surgical management of unilateral CCL rupture
Target Trial Emulation: Does surgical versus non-surgical management of cranial cruciate ligament rupture in dogs cause different outcomes?
Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Using anonymised veterinary clinical data from the VetCompass Programme, this study applied the target trial emulation framework to determine whether surgical (compared to non-surgical) management for cranial cruciate ligament (CCL) rupture in dogs causes improved short- and long-term lameness and analgesia outcomes. The emulated target trial included dogs diagnosed with CCL rupture between January 1, 2019 and December 31, 2019 within the VetCompass database. Inclusion in the emulated trial required dogs aged ≥ 1.5 and < 12 years, first diagnosed with unilateral CCL rupture during 2019 and with no prior history of contralateral ligament rupture or stifle surgery. Dogs were retrospectively observed to have surgical or non-surgical management. Informed from a directed acyclic graph derived from expert opinion, data on the following variables were collected: age, breed, bodyweight, neuter status, insurance status, non-orthopaedic comorbidities, orthopaedic comorbidities and veterinary group. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, with weights calculated based on a binary logistic regression exposure model. Censored dogs were accounted for in the IPTW analysis using inverse probability of censoring weighting (IPCW). The IPCWs were combined with IPTWs and used to weight each dog's contribution to binary logistic regression outcome models. Standardized mean differences (SMD) examined the balance of covariate distribution between treatment groups. The emulated trial included 615 surgical CCL rupture cases and 200 non-surgical cases. The risk difference for short-term lameness in surgically managed cases (compared with non-surgically managed cases) was −25.7% (95% confidence interval (CI) −36.7% to −15.9%) and the risk difference for long-term lameness −31.7% (95% CI −37.9% to −18.1%). The study demonstrated the application of the target trial framework to veterinary observational data. The findings show that surgical management causes a reduction in short- and long-term lameness compared with non-surgical management in dogs
Target trial emulation: Do antimicrobials or gastrointestinal nutraceuticals prescribed at first presentation for acute diarrhoea cause a better clinical outcome in dogs under primary veterinary care in the UK?
Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs
Trastuzumab beyond progression in HER2-positive advanced breast cancer: The Royal Marsden experience
Three agonist antibodies in combination with high-dose IL-2 eradicate orthotopic kidney cancer in mice
<p>Abstract</p> <p>Background</p> <p>Combination immunotherapies can be effective against subcutaneous tumors in mice but the effect against orthotopic malignant disease is less well characterized. In particular, a combination of three agonist antibodies, termed Tri-mAb, consisting of anti-DR5, anti-CD40 and anti-CD137 has previously been demonstrated to eradicate a large proportion of subcutaneous renal cell carcinoma (Renca) tumors (75% long-term survival), but the effect against orthotopic disease is not known.</p> <p>Purpose</p> <p>To determine the relative response of orthotopic tumors, we inoculated Renca into the kidney followed by treatment with Tri-mAb.</p> <p>Results</p> <p>We found that orthotopic tumors responded much less to treatment (~13% survival), but a significant improvement in survival was achieved through the addition of IL-2 to the treatment regimen (55% survival). All three agonist antibodies and high dose IL-2, 100,000 IU for up to six doses, were required. CD8<sup>+ </sup>T cells were also required for optimal anti-tumor responses. Coadministration of IL-2 led to enhanced T cell activity as demonstrated by an increased frequency of IFN-gamma-producing T cells in tumor-draining lymph nodes, which may have contributed to the observed improvement of therapy against kidney tumors.</p> <p>Implications</p> <p>Responses of subcutaneous tumors to immunotherapy do not necessarily reflect how orthotopic tumors respond. The use of combination immunotherapy stimulating multiple facets of immunity and including cytokine support for T cells can induce effective anti-tumor responses against orthotopic and metastatic tumors.</p
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