Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

Background: Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Methods: Pupillary light reflexes (PLR) were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate), and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. Results: The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye) compared to the left (untreated) eye at both follow-up time-points, showing stability of the improved PLR in the treated eye. Conclusions: Our method streamlined the pupillometric analyses and allowed rapid statistical analysis of a range of parameters associated with PLR. The results confirm that pupillometry is a useful objective measure for the assessment of therapeutic effect of gene therapy in patients with LCA

Caribbean plantation economies as colonial models: the case of the English East India Company and St. Helena in the late seventeenth century

In the 1680s the English East India Company (EIC) sought to develop a plantation economy in its South Atlantic colony of St. Helena, using the Caribbean island of Barbados as a colonial model. The EIC’s attempt to develop Barbadian-style plantations on St. Helena demonstrates the global reach of the Caribbean sugar colonies and their importance as an exemplar for English imperial projects in the early modern period. Colonial theorists working outside the remit of the EIC even sought to expand the Caribbean plantation system beyond the Cape of Good Hope in this period, highlighting how English overseas expansion was an interconnected phenomenon which defies rigid categorization along regional lines. Yet the failure of the EIC’s top-down plan for St. Helena also underscores how both historical contingencies and local factors were central to the success of colonial plantation, and that misunderstanding these conditions could undermine the best-laid plans and models

Addiction Professionals\u27 Attitudes Regarding Treatment of Nicotine Dependence

The objectives of this study were: to establish the extent to which addiction professionals are willing to treat nicotine addiction concurrently with other addictions, and to evaluate what factors affect their attitudes. A 21-item questionnaire was developed and distributed to therapists, physicians and other mental health workers in different treatment settings in Southeastern Virginia. CD staffers own smoking histories were significantly related to: their perceptions of the impact of nicotine use, and how likely they were to intervene in patients\u27 nicotine use. Intervention in CD staffers own smoking behavior may increase the treatment of nicotine dependence in their patients

Morphological and molecular characterisation of a mixed Cryptosporidium muris/Cryptosporidium felis infection in a cat

To date Cryptosporidium muris has been identified by microscopy and genotyping in cats in two studies. We report morphological and genetic evidence of a mixed C. muris and C. felis infection in a cat and provide the first histological, immunohistochemical, in situ hybridisation and genetic confirmation of a C. muris infection in the stomach of a cat. The cat suffered persistent diarrhoea after the initial consultation, which remained unresolved, despite several medical interventions. Further studies are required to determine the range, prevalence and clinical impact of Cryptosporidium species infecting cats

Genetic characterization of flea-derived Bartonella species from native animals in Australia suggests host-parasite co-evolution

Fleas are important arthropod vectors for a variety of diseases in veterinary and human medicine, and bacteria belonging to the genus Bartonella are among the organisms most commonly transmitted by these ectoparasites. Recently, a number of novel Bartonella species and novel species candidates have been reported in marsupial fleas in Australia. In the present study the genetic diversity of marsupial fleas was investigated; 10 species of fleas were collected from seven different marsupial and placental mammal hosts in Western Australia including woylies (Bettongia penicillata), western barred bandicoots (Perameles bougainville), mardos (Antechinus flavipes), bush rats (Rattus fuscipes), red foxes (Vulpes vulpes), feral cats (Felis catus) and rabbits (Oryctolagus cuniculus). PCR and sequence analysis of the cytochrome oxidase subunit I (COI) and the 18S rRNA genes from these fleas was performed. Concatenated phylogenetic analysis of the COI and 18S rRNA genes revealed a close genetic relationship between marsupial fleas, with Pygiopsylla hilli from woylies, Pygiopsylla tunneyi from western barred bandicoots and Acanthopsylla jordani from mardos, forming a separate cluster from fleas collected from the placental mammals in the same geographical area. The clustering of Bartonella species with their marsupial flea hosts suggests co-evolution of marsupial hosts, marsupial fleas and Bartonella species in Australia

Characterizing the entanglement of bipartite quantum systems

We derive a separability criterion for bipartite quantum systems which generalizes the already known criteria. It is based on observables having generic commutation relations. We then discuss in detail the relation among these criteria.Comment: 5 pages, 2 figures. Revised versio

Bribery, hold-up, and bureaucratic structure

We consider infrastructure provision by a foreign investor when the domestic bureaucracy is corrupt, but also cares for domestic welfare. Bureaucrats bargain with the investor over price and (potentially) bribes, both before the investment is sunk and afterwards, using the threat of expropriation. We show that domestic welfare may be greater in equilibria with bribery than in equilibria without. We specify conditions under which changes in the degree of bureaucratic centralization or of bureaucratic care have a positive, negative, or nonmonotonic effect on domestic welfare. The impact of centralization on domestic welfare is mediated through the level of bureaucratic care

Secure quantum key distribution using squeezed states

We prove the security of a quantum key distribution scheme based on transmission of squeezed quantum states of a harmonic oscillator. Our proof employs quantum error-correcting codes that encode a finite-dimensional quantum system in the infinite-dimensional Hilbert space of an oscillator, and protect against errors that shift the canonical variables p and q. If the noise in the quantum channel is weak, squeezing signal states by 2.51 dB (a squeeze factor e^r=1.34) is sufficient in principle to ensure the security of a protocol that is suitably enhanced by classical error correction and privacy amplification. Secure key distribution can be achieved over distances comparable to the attenuation length of the quantum channel.Comment: 19 pages, 3 figures, RevTeX and epsf, new section on channel losse