Supervising Offshore Outsourcing of Legal Services in a Global Environment: Re-examining Current Ethical Standards

There are many forms of legal outsourcing that range from outsourcing administrative and support functions to outsourcing legal and law-related services domestically and abroad to ―offshoring,‖ in which a firm relocates certain legal and law-related services to a foreign jurisdiction that allows the firm to realize greater efficiency and lower costs. The question is whether a distinction between the duty of supervision over the work of foreign lawyers and domestic lawyers will continue to be valid in the changing global legal environment and whether the ethical obligations under the current rules for partners, managers, and supervisory lawyers in the traditional law firm setting will remain workable when it comes to outsourcing legal work abroad

Judicial Review of Scientific Uncertainty in Climate Change Lawsuits: Deferential and Nondeferential Evaluation of Agency Factual and Policy Determinations

Scientific determinations are often at the heart of environmental disputes. When those disputes take the form of litigation, the courts may be called on to determine whether an administrative agency’s treatment of the science warrants deference. For several reasons, judges are inclined to apply deferential review to agency factual and policy science-based determinations. Most judges are not trained in the language and methods of science. They may be reluctant to intervene on matters on which their lack of expertise risks producing uninformed judgments. If a statute delegates to an agency the responsibility of making those determinations, courts may be loath to usurp that authority by substituting their judgment for the agency’s. If the statutory delegations authorize agencies to premise their decisions on the best available information, courts may regard that authorization as a signal not to take agencies to task for failing to do the impossible. Those mandates reflect a congressional judgment that agency determinations should pass judicial muster even if they fall short of conclusiveness, which may be impossible to achieve. Finally, when technical issues arise in the context of uncertainty at “the frontiers of scientific knowledge,” the Supreme Court has warned judges that highly deferential review is required.This Article describes a study analyzing cases decided by the federal courts over a period of thirty years which presented issues involving scientific uncertainty tied to climate change that arose under two key environmental statutes, the National Environmental Policy Act (NEPA) and the Endangered Species Act (ESA). The Article provides both quantitative and qualitative analysis of those cases, focusing on ascertaining the factors that drove courts to apply either deferential or non-deferential review. We found, as might be expected, that the courts applied deferential review in the majority of climate change cases arising under these two laws presenting disputes in which litigants challenged agency resolution of factual or policy matters characterized by scientific uncertainty. In the remaining cases, however, the courts, applying the arbitrary and capricious standard of judicial review, refused to defer, engaging instead in relatively rigorous review of agency science. They did so for any one of several reasons, including irrationality in agency reasoning, incomplete analysis of record science, evidentiary shortcomings, and end result-oriented reasoning. These practices induced courts to reject rote acceptance of agency pleas for deference to their scientific expertise. The Article concludes by suggesting further studies that may be useful in understanding how courts can be expected to strike the balance between deferential review and insistence that agencies provide adequate reasons for their actions in contexts of scientific uncertainty

Atomic coherent-state representation of the spectrum of scattered light from a cooperative system and numerical results

The problem of light scattering from an atomic system under cooperative conditions is analyzed. The atomic correlation function is constructed using the atomic coherent-state representation in a form that is ideally suited for numerical computations. Explicit results are reported for a system of five atoms and the question of the existence of additional side bands is analyzed

Rapid, diffusional shuttling of poly(A) RNA between nuclear speckles and the nucleoplasm

Speckles are nuclear bodies that contain pre-mRNA splicing factors and polyadenylated RNA. Because nuclear poly(A) RNA consists of both mRNA transcripts and nucleus-restricted RNAs, we tested whether poly(A) RNA in speckles is dynamic or rather an immobile, perhaps structural, component. Fluorescein-labeled oligo(dT) was introduced into HeLa cells stably expressing a red fluorescent protein chimera of the splicing factor SC35 and allowed to hybridize. Fluorescence correlation spectroscopy (FCS) showed that the mobility of the tagged poly(A) RNA was virtually identical in both speckles and at random nucleoplasmic sites. This same result was observed in photoactivation-tracking studies in which caged fluorescein-labeled oligo(dT) was used as hybridization probe, and the rate of movement away from either a speckle or nucleoplasmic site was monitored using digital imaging microscopy after photoactivation. Furthermore, the tagged poly(A) RNA was observed to rapidly distribute throughout the entire nucleoplasm and other speckles, regardless of whether the tracking observations were initiated in a speckle or the nucleoplasm. Finally, in both FCS and photoactivation-tracking studies, a temperature reduction from 37 to 22°C had no discernible effect on the behavior of poly(A) RNA in either speckles or the nucleoplasm, strongly suggesting that its movement in and out of speckles does not require metabolic energy. © 2006 by The American Society for Cell Biology

Epithelium-off corneal cross-linking surgery compared with standard care in 10- to 16-year-olds with progressive keratoconus: the KERALINK RCT

Background: Keratoconus is a disease of the cornea affecting vision that is usually first diagnosed in the first three decades. The abnormality of corneal shape and thickness tends to progress until the patient reaches approximately 30 years of age. Epithelium-off corneal cross-linking is a procedure that has been demonstrated to be effective in randomised trials in adults and observational studies in young patients. // Objectives: The KERALINK trial examined the efficacy and safety of epithelium-off corneal cross-linking, compared with standard care by spectacle or contact lens correction, for stabilisation of progressive keratoconus. // Design: In this observer-masked, randomised, controlled, parallel-group superiority trial, 60 participants aged 10–16 years with progressive keratoconus were randomised; 58 participants completed the study. Progression was defined as a 1.5 D increase in corneal power measured by maximum or mean power (K2) in the steepest corneal meridian in the study eye, measured by corneal tomography. // Setting: Referral clinics in four UK hospitals. // Interventions: Participants were randomised to corneal cross-linking plus standard care or standard care alone, with spectacle or contact lens correction as necessary for vision, and were monitored for 18 months. // Main outcome measures: The primary outcome was K2 in the study eye as a measure of the steepness of the cornea at 18 months post randomisation. Secondary outcomes included keratoconus progression, visual acuity, keratoconus apex corneal thickness and quality of life. // Results: Of 60 participants, 30 were randomised to the corneal cross-linking and standard-care groups. Of these, 30 patients in the corneal cross-linking group and 28 patients in the standard-care group were analysed. The mean (standard deviation) K2 in the study eye at 18 months post randomisation was 49.7 D (3.8 D) in the corneal cross-linking group and 53.4 D (5.8 D) in the standard-care group. The adjusted mean difference in K2 in the study eye was –3.0 D (95% confidence interval –4.93 D to –1.08 D; p = 0.002), favouring corneal cross-linking. Uncorrected and corrected differences in logMAR vision at 18 months were better in eyes receiving corneal cross-linking: –0.31 (95% confidence interval –0.50 to –0.11; p = 0.002) and –0.30 (95% confidence interval –0.48 to –0.11; p = 0.002). Keratoconus progression in the study eye occurred in two patients (7%) randomised to corneal cross-linking compared with 12 (43%) patients randomised to standard care. The unadjusted odds ratio suggests that, on average, patients in the corneal cross-linking group had 90% (odds ratio 0.1, 95% confidence interval 0.02 to 0.48; p = 0.004) lower odds of experiencing progression than those receiving standard care. Quality-of-life outcomes were similar in both groups. No adverse events were attributable to corneal cross-linking. // Limitations: Measurements of K2 in those eyes with the most significant progression were in some cases indicated as suspect by corneal topography device software. // Conclusions: Corneal cross-linking arrests progression of keratoconus in the great majority of young patients. These data support a consideration of a change in practice, such that corneal cross-linking could be considered as first-line treatment in progressive disease. If the arrest of keratoconus progression induced by corneal cross-linking is sustained in longer follow-up, there may be particular benefit in avoiding the later requirement for contact lens wear or corneal transplantation. However, keratoconus does not continue to progress in all patients receiving standard care. For future work, the most important questions to be answered are whether or not (1) the arrest of keratoconus progression induced by corneal cross-linking is maintained in the long term and (2) the proportion of those receiving standard care who show significant progression increases with time

Novel disease-causing variants and phenotypic features of X-linked megalocornea

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. // Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. // Results: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). // Conclusion: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants

Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene

BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family. RESULTS: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested. CONCLUSION: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children

IPSC-Derived Corneal Endothelial-like Cells Act as an Appropriate Model System to Assess the Impact of SLC4A11 Variants on Pre-mRNA Splicing

Purpose: To report molecular genetic findings in six probands with congenital hereditary endothelial dystrophy (CHED) variably associated with hearing loss (also known as Harboyan syndrome). Furthermore, we developed a cellular model to determine if disease-associated variants induce aberrant SLC4A11 pre-mRNA splicing. Methods: Direct sequencing of the entire SLC4A11 coding region was performed in five probands. In one individual, whole genome sequencing was undertaken. The effect of c.2240+5G>A on pre-mRNA splicing was evaluated in a corneal endothelial-like (CE-like) cell model expressing SLC4A11. CE-like cells were derived from autologous induced pluripotent stem cells (iPSCs) via neural crest cells exposed to B27, PDGF-BB, and DKK-2. Total RNA was extracted, and RT-PCR was performed followed by Sanger and a targeted next generation sequencing (NGS) approach to identify and quantify the relative abundance of alternatively spliced transcripts. Results: In total, 11 different mutations in SLC4A11 evaluated as pathogenic were identified; of these, c.1237G>A, c.2003T>C, c.1216+1G>A, and c.2240+5G>A were novel. The c.2240+5G>A variant was demonstrated to result in aberrant pre-mRNA splicing. A targeted NGS approach confirmed that the variant introduces a leaky cryptic splice donor site leading to the production of a transcript containing an insertion of six base pairs with the subsequent introduction of a premature stop codon (p.Thr747*). Furthermore, a subset of transcripts comprising full retention of intron 16 also were observed, leading to the same functionally null allele. Conclusions: This proof-of-concept study highlights the potential of using CE-like cells to investigate the pathogenic consequences of SLC4A11 disease-associated variants

Stemming the tide: progress towards resolving the causes of decline and implementing management responses for the disappearing mammal fauna of northern Australia

Introduction: Recent studies at sites in northern Australia have reported severe and rapid decline of several native mammal species, notwithstanding an environmental context (small human population size, limited habitat loss, substantial reservation extent) that should provide relative conservation security. All of the more speciose taxonomic groups of mammals in northern Australia have some species for which their conservation status has been assessed as threatened, with 53 % of dasyurid, 47 % of macropod and potoroid, 33 % of bandicoot and bilby, 33 % of possum, 30 % of rodent, and 24 % of bat species being assessed as extinct, threatened or near threatened. However, the geographical extent and timing of declines, and their causes, remain poorly resolved, limiting the application of remedial management actions.\ud \ud Material and methods: Focusing on the tropical savannas of northern Australia, this paper reviews disparate recent and ongoing studies that provide information on population trends across a broader geographic scope than the previously reported sites, and examines the conservation status and trends for mammal groups (bats, macropods) not well sampled in previous monitoring studies. It describes some diverse approaches of studies seeking to document conservation status and trends, and of the factors that may be contributing to observed patterns of decline.\ud \ud Results and Discussion: Current trends and potential causal factors for declines. The studies reported demonstrate that the extent and timing of impacts and threats have been variable across the region, although there is a general gradational pattern of earlier and more severe decline from inland lower rainfall areas to higher rainfall coastal regions. Some small isolated areas appear to have retained their mammal species, as have many islands which remain critical refuges. There is now some compelling evidence that predation by feral cats is implicated in the observed decline, with those impacts likely to be exacerbated by prevailing fire regimes (frequent, extensive and intense fire), by reduction in ground vegetation cover due to livestock and, in some areas, by 'control' of dingoes. However the impacts of dingoes may be complex, and are not yet well resolved in this area. The relative impacts of these individual factors vary spatially (with most severe impacts in higher rainfall and more rugged areas) and between different mammal species, with some species responding idiosyncratically: the most notable example is the rapid decline of the northern quoll (Dasyurus hallucatus) due to poisoning by the introduced cane toad (Rhinella marina), which continues to spread extensively across northern Australia. The impact of disease, if any, remains unresolved.\ud \ud Conservation Management Responses. Recovery of the native mammal fauna may be impossible in some areas. However, there are now examples of rapid recovery following threat management. Priority conservation actions include: enhanced biosecurity for important islands, establishment of a network of feral predator exclosures, intensive fire management (aimed at increasing the extent of longer-unburnt habitat and in delivering fine scale patch burning), reduction in feral stock in conservation reserves, and acquisition for conservation purposes of some pastoral lands in areas that are significant for mammal conservation

Geographical variations in the benefit of applying a prioritization system for cataract surgery in different regions of Spain

<p>Abstract</p> <p>Background</p> <p>In Spain, there are substantial variations in the utilization of health resources among regions. Because the need for surgery differs in patients with appropriate surgical indication, introducing a prioritization system might be beneficial. Our objective was to assess geographical variations in the impact of applying a prioritization system in patients on the waiting list for cataract surgery in different regions of Spain by using a discrete-event simulation model.</p> <p>Methods</p> <p>A discrete-event simulation model to evaluate demand and waiting time for cataract surgery was constructed. The model was reproduced and validated in five regions of Spain and was fed administrative data (population census, surgery rates, waiting list information) and data from research studies (incidence of cataract). The benefit of introducing a prioritization system was contrasted with the usual first-in, first-out (FIFO) discipline. The prioritization system included clinical, functional and social criteria. Priority scores ranged between 0 and 100, with greater values indicating higher priority. The measure of results was the waiting time weighted by the priority score of each patient who had passed through the waiting list. Benefit was calculated as the difference in time weighted by priority score between operating according to waiting time or to priority.</p> <p>Results</p> <p>The mean waiting time for patients undergoing surgery according to the FIFO discipline varied from 1.97 months (95% CI 1.85; 2.09) in the Basque Country to 10.02 months (95% CI 9.91; 10.12) in the Canary Islands. When the prioritization system was applied, the mean waiting time was reduced to a minimum of 0.73 months weighted by priority score (95% CI 0.68; 0.78) in the Basque Country and a maximum of 5.63 months (95% CI 5.57; 5.69) in the Canary Islands. The waiting time weighted by priority score saved by the prioritization system varied from 1.12 months (95% CI 1.07; 1.16) in Andalusia to 2.73 months (95% CI 2.67; 2.80) in Aragon.</p> <p>Conclusion</p> <p>The prioritization system reduced the impact of the variations found among the regions studied, thus improving equity. Prioritization allocates the available resources within each region more efficiently and reduces the waiting time of patients with greater need. Prioritization was more beneficial than allocating surgery by waiting time alone.</p