Are some teat disinfectant formulations more effective against specific bacteria isolated on teat skin than others?

peer-reviewedThe use of pre- and post-milking teat disinfectants can reduce teat bacterial load and aid in the collection of high-quality milk. The objective of this study was to compare the reduction in bacteria populations on teat skin after the application of different commercial teat disinfectant products. Ten teat disinfectant products were applied to the teats of 10 Holstein–Friesian cows. One cow received one teat disinfectant product at each sampling point before cluster application for milking. A composite swab sample was taken of the 4 teats of each cow before and after teat disinfectant application. Swab samples were placed on three different selective agars to enumerate bacterial counts of staphylococcal, streptococcal and coliforms isolates on teat skin. Staphylococcal isolates were the most prominent bacterial group recovered on teat swabs (49%), followed by streptococcal (36%) and coliform (15%) isolates before the application of disinfectant. The average bacterial reductions on teat skin were shown to be 76%, 73% and 60% for staphylococcal, streptococcal and coliform isolates, respectively. All of the teat disinfectant products tested reduced teat bacterial load for all three bacterial groups. Product 4 containing 0.6% w/w diamine was the most effective against bacterial populations of staphylococcal and streptococcal isolates on teat skin with a reduction of 90% and 94%, respectively. Whereas product 10, which contained 0.5% w/w iodine, resulted in the highest reduction in coliforms on teat skin with a reduction of 91%. Results from this study suggest that specific bacterial population loads on teats can be reduced using different teat disinfectant formulations

Integrating serological and genetic data to quantify cross-species transmission: brucellosis as a case study

Epidemiological data are often fragmented, partial, and/or ambiguous and unable to yield the desired level of understanding of infectious disease dynamics to adequately inform control measures. Here, we show how the information contained in widely available serology data can be enhanced by integration with less common type-specific data, to improve the understanding of the transmission dynamics of complex multi-species pathogens and host communities. Using brucellosis in Northern Tanzania as a case-study, we developed a latent process model based on serology data obtained from the field, to reconstruct Brucella transmission dynamics. We were able to identify sheep and goats as a more likely source of human and animal infection than cattle; however, the highly cross-reactive nature of Brucella spp. meant that it was not possible to determine which Brucella species (B. abortus or B. melitensis) is responsible for human infection. We extended our model to integrate simulated serology and typing data, and show that although serology alone can identify the host source of human infection under certain restrictive conditions, the integration of even small amounts (5%) of typing data can improve understanding of complex epidemiological dynamics. We show that data integration will often be essential when more than one pathogen is present and when the distinction between exposed and infectious individuals is not clear from serology data. With increasing epidemiological complexity, serology data become less informative. However, we show how this weakness can be mitigated by integrating such data with typing data, thereby enhancing the inference from these data and improving understanding of the underlying dynamics

Occupational therapy for people with psychotic conditions in community settings: a pilot randomized controlled trial

OBJECTIVES: To investigate the effectiveness of a long established intervention, occupational therapy for people with psychotic conditions, and to inform future research designs. DESIGN: A pilot randomized controlled trial. SETTING: Two community mental health teams in a UK city. PARTICIPANTS: Forty-four adults with schizophrenia or other psychotic conditions, and functional problems. INTERVENTIONS: Twelve months of individualized occupational therapy in community settings, as an adjunct to usual care and compared to treatment as usual. A two to one randomization ratio was used in favour of occupational therapy. OUTCOME MEASURES: Social Functioning Scale, Scale for the Assessment of Negative Symptoms and employment. RESULTS: Both groups' scores on Social Functioning Scale and Scale for the Assessment of Negative Symptoms showed significant improvement over 12 months. The Social Functioning Scale overall mean difference for occupational therapy was 2.33, P=0.020 and for treatment as usual was 6.17, P=0.023. The Scale for the Assessment of Negative Symptoms total mean difference for occupational therapy was -16.25, P<0.001 and for treatment as usual was -17.36, P= 0.011. There were no differences between the two groups on any of the outcome measures. After 12 months the occupational therapy group showed clinically significant improvements that were not apparent in the control group. These were in four subscales of the Social Functioning Scale: relationships, independence performance, independence competence and recreation. Out of 30 people receiving occupational therapy those with a clinical level of negative symptoms reduced from 18 (64%) to 13 (46%), P=0.055. CONCLUSION: This pilot study suggested that individualized occupatio

The effect of disinfectant ingredients on teat skin bacteria associated with mastitis in Irish dairy herds

peer-reviewedBackground Teat disinfection is an important step in the control of mastitis within a dairy herd. The objective of this study was to evaluate the effectiveness of 96 commercially available teat disinfectant products in Ireland against bacterial isolates on teat skin. Teat disinfection products were applied to the teats of seventeen Holstein–Friesian cows. A split-udder model was used where one cow received two different teat disinfection products on each day. A composite swab sample was taken of the left teats and the right teats before and after teat disinfectant application. Swab samples were plated onto 3 different selective agars to enumerate bacterial counts of streptococcal, staphylococcal and coliform isolates. Results Streptococcal isolates were the most prominent bacterial group recovered on teat swabs taken before the application of a teat disinfection product (55.0%), followed by staphylococcal isolates (41.3%) and coliform isolates (3.7%). Products were reclassified by active ingredients (n = 9) for analysis. These ingredient groups included; chlorhexidine, chlorine dioxide, diamine, iodine, iodine and lactic acid, lactic acid, lactic acid and chlorhexidine, lactic acid and hydrogen peroxide, and lactic acid and salicylic acid. The ingredient group, chlorine dioxide, resulted in comparable reductions to the iodine group for streptococcal isolates. The ingredient group, iodine combined with lactic acid, resulted in the greatest reduction of staphylococcal isolates. When observing products individually, a product containing 1.6% w/w lactic acid combined with hydrogen peroxide was the most effective at reducing streptococcal isolates on the teat skin, whereas a product containing lactic acid combined with 0.6% w/w chlorhexidine was the most effective against staphylococcal isolates. Minor differences were observed regarding the relationship between effectiveness and active ingredient concentration between products. Conclusions This study suggests that some teat disinfectant products achieve a higher reduction in bacterial levels against different specific bacterial groups on teat skin than other products. Therefore, when choosing a teat disinfectant product, the bacteria in the dairy herds’ environment should be considered. Further studies are necessary to evaluate products efficacy against new IMIs and any possible effects on teat skin condition

Robustness to misalignment of low-cost, compact quantitative phase imaging architectures.

Non-interferometric approaches to quantitative phase imaging could enable its application in low-cost, miniaturised settings such as capsule endoscopy. We present two possible architectures and both analyse and mitigate the effect of sensor misalignment on phase imaging performance. This is a crucial step towards determining the feasibility of implementing phase imaging in a capsule device. First, we investigate a design based on a folded 4f correlator, both in simulation and experimentally. We demonstrate a novel technique for identifying and compensating for axial misalignment and explore the limits of the approach. Next, we explore the implications of axial and transverse misalignment, and of manufacturing variations on the performance of a phase plate-based architecture, identifying a clear trade-off between phase plate resolution and algorithm convergence time. We conclude that while the phase plate architecture is more robust to misalignment, both architectures merit further development with the goal of realising a low-cost, compact system for applying phase imaging in capsule endoscopy

Detecting cryptic clinically relevant structural variation in exome-sequencing data increases diagnostic yield for developmental disorders.

Structural variation (SV) describes a broad class of genetic variation greater than 50 bp in size. SVs can cause a wide range of genetic diseases and are prevalent in rare developmental disorders (DDs). Individuals presenting with DDs are often referred for diagnostic testing with chromosomal microarrays (CMAs) to identify large copy-number variants (CNVs) and/or with single-gene, gene-panel, or exome sequencing (ES) to identify single-nucleotide variants, small insertions/deletions, and CNVs. However, individuals with pathogenic SVs undetectable by conventional analysis often remain undiagnosed. Consequently, we have developed the tool InDelible, which interrogates short-read sequencing data for split-read clusters characteristic of SV breakpoints. We applied InDelible to 13,438 probands with severe DDs recruited as part of the Deciphering Developmental Disorders (DDD) study and discovered 63 rare, damaging variants in genes previously associated with DDs missed by standard SNV, indel, or CNV discovery approaches. Clinical review of these 63 variants determined that about half (30/63) were plausibly pathogenic. InDelible was particularly effective at ascertaining variants between 21 and 500 bp in size and increased the total number of potentially pathogenic variants identified by DDD in this size range by 42.9%. Of particular interest were seven confirmed de novo variants in MECP2, which represent 35.0% of all de novo protein-truncating variants in MECP2 among DDD study participants. InDelible provides a framework for the discovery of pathogenic SVs that are most likely missed by standard analytical workflows and has the potential to improve the diagnostic yield of ES across a broad range of genetic diseases

Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation

RAB18, RAB3GAP1, RAB3GAP2 and TBC1D20 are each mutated in Warburg Micro syndrome, a rare autosomal recessive multisystem disorder. RAB3GAP1 and RAB3GAP2 form a binary ‘RAB3GAP’ complex that functions as a guanine-nucleotide exchange factor (GEF) for RAB18, whereas TBC1D20 shows modest RAB18 GTPase-activating (GAP) activity in vitro. Here, we show that in the absence of functional RAB3GAP or TBC1D20, the level, localization and dynamics of cellular RAB18 is altered. In cell lines where TBC1D20 is absent from the endoplasmic reticulum (ER), RAB18 becomes more stably ER-associated and less cytosolic than in control cells. These data suggest that RAB18 is a physiological substrate of TBC1D20 and contribute to a model in which a Rab-GAP can be essential for the activity of a target Rab. Together with previous reports, this indicates that Warburg Micro syndrome can be caused directly by loss of RAB18, or indirectly through loss of RAB18 regulators RAB3GAP or TBC1D20

Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate

Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Étude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations

Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP.

We aimed to develop an efficient, flexible and scalable approach to diagnostic genome-wide sequence analysis of genetically heterogeneous clinical presentations. Here we present G2P ( www.ebi.ac.uk/gene2phenotype ) as an online system to establish, curate and distribute datasets for diagnostic variant filtering via association of allelic requirement and mutational consequence at a defined locus with phenotypic terms, confidence level and evidence links. An extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P was used to filter both disease-associated and control whole exome sequence (WES) with Developmental Disorders G2P (G2PDD; 2044 entries). VEP-G2PDD shows a sensitivity/precision of 97.3%/33% for de novo and 81.6%/22.7% for inherited pathogenic genotypes respectively. Many of the missing genotypes are likely false-positive pathogenic assignments. The expected number and discriminative features of background genotypes are defined using control WES. Using only human genetic data VEP-G2P performs well compared to other freely-available diagnostic systems and future phenotypic matching capabilities should further enhance performance