Early Diagnosis, Treatment and Follow-Up of Cystic Echinococcosis in Remote Rural Areas in Patagonia: Impact of Ultrasound Training of Non-Specialists

Cystic echinococcosis (CE) is an important and widespread disease that affects sheep, cattle, and humans living in areas where sheep and cattle are raised. CE is highly endemic in rural sections of Rio Negro, Argentina, where our group is based. However, it requires continuous monitoring of both populations with human disease best assessed by means of ultrasound (US) screening. This is challenging in remote rural areas due to the shortage of imaging specialists. To overcome this hurdle, we set up a two-day training program of Focused Assessment with Sonography for Echinococcosis (FASE) on CE for family medicine practitioners with no previous experience in US. After the course, they were equipped with portable US scanners and dispatched to remote rural areas in Rio Negro where they screened patients, located and staged the cysts and decided on the treatment with the help of surgeons and radiologists in local tertiary care centers

Challenges in dengue research: A computational perspective

This is the final version of the article. Available from Wiley via the DOI in this record.The dengue virus is now the most widespread arbovirus affecting human populations, causing significant economic and social impact in South America and South-East Asia. Increasing urbanization and globalization, coupled with insufficient resources for control, misguided policies or lack of political will, and expansion of its mosquito vectors are some of the reasons why interventions have so far failed to curb this major public health problem. Computational approaches have elucidated on dengue's population dynamics with the aim to provide not only a better understanding of the evolution and epidemiology of the virus but also robust intervention strategies. It is clear, however, that these have been insufficient to address key aspects of dengue's biology, many of which will play a crucial role for the success of future control programmes, including vaccination. Within a multiscale perspective on this biological system, with the aim of linking evolutionary, ecological and epidemiological thinking, as well as to expand on classic modelling assumptions, we here propose, discuss and exemplify a few major computational avenues—real-time computational analysis of genetic data, phylodynamic modelling frameworks, within-host model frameworks and GPU-accelerated computing. We argue that these emerging approaches should offer valuable research opportunities over the coming years, as previously applied and demonstrated in the context of other pathogens.JL, AW and SG received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement no. 268904 - DIVERSITY. MR was supported by a Royal Society University Research Fellowship. NRF by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204311/Z/16/Z). WT has received funding from a doctoral scholarship from the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership

Schottky barrier lowering with the formation of crystalline Er silicide on n-Si upon thermal annealing

The evolution of the Schottky barrier height (SBH) of Er silicide contacts to n-Si is investigated as a function of the annealing temperature. The SBH is found to drop substantially from 0.43 eV for the as-deposited sample to reach 0.28 eV, its lowest value, at 450 C. By x-ray diffraction, high resolution transmission electron microscopy, and x-ray photoelectron spectroscopy, the decrease in the SBH is shown to be associated with the progressive formation of crystalline ErSi2-x

Post-treatment follow-up study of abdominal cystic echinococcosis in Tibetan communities of northwest Sichuan Province, China

Background: Human cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, with the liver as the most frequently affected organ, is known to be highly endemic in Tibetan communities of northwest Sichuan Province. Antiparasitic treatment with albendazole remains the primary choice for the great majority of patients in this resource-poor remote area, though surgery is the most common approach for CE therapy that has the potential to remove cysts and lead to complete cure. The current prospective study aimed to assess the effectiveness of community based use of cyclic albendazole treatment in Tibetan CE cases, and concurrently monitor the changes of serum specific antibody levels during treatment. Methodology/Principal Findings: Ultrasonography was applied for diagnosis and follow-up of CE cases after cyclic albendazole treatment in Tibetan communities of Sichuan Province during 2006 to 2008, and serum specific IgG antibody levels against Echinococcus granulosus recombinant antigen B in ELISA was concurrently monitored in these cases. A total of 196 CE cases were identified by ultrasound, of which 37 (18.9%) showed evidence of spontaneous healing/involution of hepatic cyst(s) with CE4 or CE5 presentations. Of 49 enrolled CE cases for treatment follow-up, 32.7% (16) were considered to be cured based on B-ultrasound after 6 months to 30 months regular albendazole treatment, 49.0% (24) were improved, 14.3% (7) remained unchanged, and 4.1% (2) became aggravated. In general, patients with CE2 type cysts (daughter cysts present) needed a longer treatment course for cure (26.4 months), compared to cases with CE1 (univesicular cysts) (20.4 months) or CE3 type (detached cyst membrane or partial degeneration of daughter cysts) (9 months). In addition, the curative duration was longer in patients with large (.10 cm) cysts (22.3 months), compared to cases with medium (5– 10 cm) cysts (17.3 months) or patients with small (,5 cm) cysts (6 months). At diagnosis, seven (53.8%) of 13 cases with CE1 type cysts without any previous intervention showed negative specific IgG antibody response to E. granulosus recombinant antigen B (rAgB). However, following 3 months to 18 months albendazole therapy, six of these 7 initially seronegative CE1 cases sero-converted to be specific IgG antibody positive, and concurrently ultrasound scan showed that cysts changed to CE3a from CE1 type in all the six CE cases. Two major profiles of serum specific IgG antibody dynamics during albendazole treatment were apparent in CE cases: (i) presenting as initial elevation followed by subsequent decline, or (ii) a persistent decline. Despite a decline, however, specific antibody levels remained positive in most improved or cured CE cases. Conclusions: This was the first attempt to follow up community-screened cystic echinococcosis patients after albendazole therapy using ultrasonography and serology in an endemic Tibetan region. Cyclic albendazole treatment proved to be effective in the great majority of CE cases in this resource-poor area, but periodic abdominal ultrasound examination was necessary to guide appropriate treatment. Oral albendazole for over 18 months was more likely to result in CE cure. Poor drug compliance resulted in less good outcomes. Serology with recombinant antigen B could provide additional limited information about the effectiveness of albendazole in CE cases. Post-treatment positive specific IgG antibody seroconversion, in initially seronegative, CE1 patients was considered a good indication for positive therapeutic efficacy of albendazole

Evaluation of serological tests for Trichinella infections in pigs

The Dutch slaughter pig population is practically free of Trichinella spiralis. However, at slaughter every pig is tested for presence of larvae using the digestion method for export certification . A new 2006 EU directive concerning meat inspection for Trichinella spp. offers new opportunities to monitor Trichinella at herd level instead. Also serological methods are allowed when approved by the Commumty Reference Laboratory (CRL). To evaluate the usefulness of serological tests for momtoring a virtually free population for Trichinella, Bayesian methodology was used to estimate the diagnostic test parameters sensitivity and specificity, in the absence of a Gold Standard test

Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.

The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage

The influence of localised size reorganisation on short-duration bidispersed granular flows

We investigate experimentally the runout resulting from the collapse of a granular column containing two particle species that differ in size only. The experimental configuration is strictly twodimensional (only one particle per width of the experimental tank) and we explore both the role of the initial arrangement and proportion of the two particle sizes in the column, using high-speed videography, and by determining the centres of mass of the big and small particles in the initial column and the final deposit. The duration of the experiment is sufficiently short that large-scale segregation does not occur, however, we find a clear dependence of runout on both initial mixture arrangement and proportion for all conditions. We investigated this observation through detailed analysis of the flow front motion, and identify a characteristic "stopping" phase when dissipation dominates, and we apply a shallow layer model at the flow front to show how the initial mixture arrangement and proportion influence the effective coefficient of friction during emplacement. We find that a bidispersed mixture can induce a larger friction on emplacement than a monodispersed mixture, and the highest coefficient of friction was found for a well-mixed initial arrangement of particles at the proportion that shows maximum horizontal spreading of the flow. These observations suggest that downwards percolation of fine particles takes place at the front of the collapsing column, and so localised size segregation processes at the flow front can control flow mobility. This effect is likely to be important in controlling the mobility of large geophysical flows that occur on finite time scales, and whose deposits typically show granular segregation at the front and edges but not throughout the entire deposit

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. METHODS AND RESULTS: We report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide-one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T>A mutation in blood DNA and a c.1968+2T>C in DNA from cultured fibroblasts. Deep sequencing of DNA from the proband's blood revealed 4.7% c.1968+2T>C mutation, and 41.3% c.1968+2T>A mutation. CONCLUSIONS: We hypothesise that the germline mutation was c.1968+2T>A, but a rescue event occurred during early development, where the somatic mutation from A to C at 1968+2 provided a selective advantage. This type of mosaicism where a partial phenotypic rescue event results from a second but milder disease-causing mutation in the same nucleotide has not been previously characterised for any disease.Progeria experiments were funded by The Progeria Research Foundation grants PRF-2002-CB and PRF-2002-MRD (JFB, WEN, SEC, LBG), and by the Medical Research Council UK grant MR/L019116/1 (DL). Core and general laboratory grants are as follows: Kilguss Research Core of Women & Infants Hospital of Rhode Island through an Institutional Development Award from the NIGMS of the NIH (P30GM114750), intramural funds to the NHGRI (ZIA-HG200305), Cancer Research UK programme grant C6/A18796 and Wellcome Trust (WT092096)