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1.
Digit Health ; 10: 20552076241242328, 2024.
Article in English | MEDLINE | ID: mdl-38550260

ABSTRACT

Objective: Caregivers raising children with fetal alcohol spectrum disorders (FASD) have limited access to evidence-based supports. This single-arm feasibility trial assesses the Families Moving Forward (FMF) Connect app to determine readiness for a larger randomized controlled trial (RCT). Methods: Eligibility for this online trial included caregivers of children (ages 3-12) with FASD residing in the United States. Caregivers received FMF Connect for 12 weeks on their personal smartphones (iOS or Android). Pre- and post-assessments included child behavior, parenting and family functioning, and app quality; user experience interviews were conducted post-intervention. Usage and crashes were monitored. Study objectives assessed feasibility of the trial (recruitment, attrition, measure sensitivity), intervention (technical functionality, acceptability), and implementation (caregiver usage). Results: Recruitment strategies proved sufficient with 171 caregivers screened and 105 deemed eligible. Analyses identified a few predictive demographic and outcome variables related to attrition. Several study measures were sensitive to change. Additional trial and measurement improvements were identified. From a technological perspective, the FMF Connect app was functional; the Android prototype required more.

2.
Aust Vet J ; 102(6): 285-292, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38342502

ABSTRACT

INTRODUCTION: Reducing antibiotic use in production animal systems is one strategy which may help to limit the development of antimicrobial resistance. To reduce antimicrobial use in food-producing animals, it is important to first understand how antibiotics are used on farm and what barriers exist to decreasing their use. In dairy production systems, mastitis is one of the most common reasons for administering antimicrobials. Therefore, it is important to understand the motivations and behaviours of dairy farmers in relation to the diagnosis, treatment and prevention of mastitis. MATERIALS AND METHODS: In this study, we interviewed a sample of dairy farmers and dairy industry professionals from the major dairying regions of eastern Australia regarding their current practices used to diagnose, treat, and control subclinical and clinical mastitis. Inductive thematic analysis was used to code interview transcripts and identify the recurrent themes. RESULTS: Four overarching themes were identified: (1) the challenges associated with the detection and diagnosis of clinical mastitis, including with laboratory culture, (2) the motivations behind treatment decisions for different cases, (3) decisions around dry cow therapy and the role of herd recording, and (4) concerns regarding the development of antimicrobial resistance. DISCUSSION: This study identifies several challenges which may limit the ability of Australian dairy farmers to reduce antimicrobial use on farm, such as the need for rapid and reliable diagnostic tests capable of identifying the pathogenic causes of mastitis and the difficulties associated with conducting herd recording for the implementation of selective dry cow therapy. Industry professionals were concerned that farmers were not using individual cow records to aid in treatment decisions, which could result in unnecessary antimicrobial use. The results of this study can act as the basis for future research aimed at assessing these issues across the broader Australian dairy industry.


Subject(s)
Dairying , Farmers , Mastitis, Bovine , Animals , Cattle , Dairying/methods , Female , Australia , Mastitis, Bovine/prevention & control , Mastitis, Bovine/drug therapy , Farmers/psychology , Anti-Bacterial Agents/therapeutic use , Humans
3.
Leukemia ; 38(4): 720-728, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38360863

ABSTRACT

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.


Subject(s)
Burkitt Lymphoma , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Young Adult , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Risk Assessment , Disease-Free Survival
4.
Phys Chem Chem Phys ; 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37464810

ABSTRACT

Li7La3Zr2O12 (LLZO) and related ceramic solid electrolytes feature excellent stability and reasonable ionic conductivity, but processing remains challenging. High-temperature co-sintering is required for successful integration with the electrode, which is energetically costly and can lead to unacceptable cathode degradation. The introduction of dopants can promote lower-temperature processing by improving deformability and disrupting lattice integrity; however, an unbiased, systematic study correlating these properties to the dopant chemistry and composition is lacking. Here, we rely on a set of static and dynamic metrics derived from first-principles simulations to estimate the impact of doping on LLZO processability by quantifying LLZO structural deformability. We considered three distinct dopants (Al, Ba, and Ta) as representatives of substitutional incorporation on Li, La, and Zr sites. Our descriptors indicate that doping in general positively impacts lattice deformability, although significant sensitivities to dopant identity and concentration are observed. Amongst the tested dopants, Al doping (on the Li site) appears to have the greatest impact, as signaled across nearly the entire set of computed features. We suggest that these proxy descriptors, once properly calibrated against well-controlled experiments, could enable the use of first-principles simulations to computationally screen new ceramic electrolyte compositions with improved processability.

5.
Poult Sci ; 101(3): 101648, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35093770

ABSTRACT

Biobanked poultry ovaries can be revived via transplantation into a recipient female, which upon maturity will produce donor-derived progeny. Previously, a large portion of these recipients also produced recipient-derived progeny, making them gonadal chimeras. These were potentially created when portions of the recipient's ovary were inadvertently left behind. Completely removing the recipient ovary would solve this problem; however, leaving a portion of the recipient's ovary may have inadvertently increased the transplant attachment rate by providing a damaged area for attachment. To test this hypothesis in the turkey, we removed various portions (33-100%) of recipient ovarian tissue and determined the transplant attachment rate. Furthermore, the use of the abdominal air sac membrane as an additional anchoring point was tested. The overall attachment rate of transplants was 91% (27/30), while the average size of the transplants was 4.2 ± 0.6 mm2, 6 d postsurgery. There was no difference (P > 0.05) in the attachment rates, or transplant size between groups with varying amounts of recipent tissue removed, or by using the abdominal air sac membrane as an anchor. Finally, the immunological status of the grafts were evaluated by analyzing the presences of CD3 and MUM-1 (T and B cell markers). This showed that all transplants were infiltrated by large numbers of T and B cells. Shown by a high (P ≤ 0.001) percentage of CD3-positive immunostained cytoplasmic area (49.78 ± 3.90%) in transplants compared to remnant recipient tissue (0.30 ± 0.10%), as well as a high (P ≤ 0.001) percentage of MUM-1-positive immunostained nuclear area (9.85 ± 1.95%) in transplants over remnant recipient tissues (0.39 ± 0.12%). From this study we would recommend removing the entire recipient ovary, and not covering the transplants with the abdominal air sac membrane, to prevent gonadal chimeras. The high levels of lymphocytes within the grafts indicate possible tissue rejection, which could be overcome via immunosuppression with or without histocompatibility matching between donors and recipients.


Subject(s)
Chickens , Ovary , Animals , Female , Humans , Immunosuppression Therapy/veterinary , Tissue Donors
6.
Poult Sci ; 101(2): 101601, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34954445

ABSTRACT

Pendulous crop (PC) in the turkey occurs when the crop distends from its normal position, thereby preventing the movement of feed and water from the crop down into the digestive system. This condition negatively impacts the turkey industry at both production and welfare levels. In this study, we estimated the genetic parameters for PC incidence and its genetic correlation with 5 production traits. Additionally, we evaluated the prediction accuracy and bias of breeding values for the selection candidates using pedigree (BLUP) or pedigree-genomic (ssGBLUP) relationships among the animals. A total of 245,783 turkey records were made available by Hybrid Turkeys, Kitchener, Canada. Of these, 6,545 were affected with PC. In addition, the data included 9,634 records for breast meat yield (BMY); 5,592 records for feed conversion ratio (FCR) and residual feed intake (RFI) in males; 170,844 records for body weight (BW) and walking score (WS) between 18 and 20 wk of age for males (71,012) and females (99,832), respectively. Among this population, 36,830 were genotyped using a 65K SNP Illumina Inc. chip. While all animals passed the quality control criteria, only 53,455 SNP markers were retained for subsequent analysis. Heritability for PC was estimated at 0.16 ± 0.00 and 0.17 ± 0.00 using BLUP and ssGBLUP, respectively. The incidence of PC was not genetically correlated with WS or FCR. Low unfavourable genetic correlations with BW (0.12 and 0.14), BMY (0.24 and 0.24) and RFI (-0.33 and -0.28) were obtained using BLUP and ssGBLUP, respectively. Using ssGBLUP showed higher prediction accuracy (0.51) for the breeding values for the selection candidates than the pedigree-based model (0.35). Whereas the bias of the prediction was slightly reduced with ssGBLUP (0.33 ± 0.05) than BLUP (0.30 ± 0.08), both models showed a regression coefficient lower than one, indicating inflation in the predictions. The results of this study suggest that PC is a heritable trait and selection for lower PC incidence rates is feasible. Although further investigation is necessary, selection for BW, BMY, and RFI may increase PC incidence. Incorporating genomic information would lead to higher accuracy in predicting the genetic merit for selection candidates.


Subject(s)
Models, Genetic , Turkeys , Animals , Body Weight , Chickens , Female , Genomics , Genotype , Male , Pedigree , Phenotype , Turkeys/genetics
7.
Sci Rep ; 11(1): 17018, 2021 08 23.
Article in English | MEDLINE | ID: mdl-34426640

ABSTRACT

Insights into potential differences among the bony labyrinths of Plio-Pleistocene hominins may inform their evolutionary histories and sensory ecologies. We use four recently-discovered bony labyrinths from the site of Kromdraai to significantly expand the sample for Paranthropus robustus. Diffeomorphometry, which provides detailed information about cochlear shape, reveals size-independent differences in cochlear shape between P. robustus and Australopithecus africanus that exceed those among modern humans and the African apes. The cochlea of P. robustus is distinctive and relatively invariant, whereas cochlear shape in A. africanus is more variable, resembles that of early Homo, and shows a degree of morphological polymorphism comparable to that evinced by modern species. The curvature of the P. robustus cochlea is uniquely derived and is consistent with enhanced sensitivity to low-frequency sounds. Combined with evidence for selection, our findings suggest that sound perception shaped distinct ecological adaptations among southern African early hominins.


Subject(s)
Cochlea/anatomy & histology , Hearing/physiology , Hominidae/classification , Phylogeny , Animals , Fossils , Principal Component Analysis , South Africa
8.
Anal Methods ; 13(26): 3001, 2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34128003

ABSTRACT

Correction for 'Empirical study on the effects of acquisition parameters for FTIR hyperspectral imaging of brain tissue' by J. Sacharz et al., Anal. Methods, 2020, 12, 4334-4342, DOI: 10.1039/C9AY01200A.

9.
J Appl Microbiol ; 130(3): 982-993, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32780423

ABSTRACT

AIMS: Attenuated Total Reflection Fourier Transform Infrared (ATR-FT-IR) Spectroscopy and chemometric modelling, including soft independent modelling by class analogy (SIMCA), partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM), were applied to attempt to discriminate 60 clinical isolates of Enterococcus faecium and Enterococcus faecalis and hence evaluate the performance of the spectroscopic approach in identifying enterococci infections. METHODS AND RESULTS: The bacterial samples were identified by polymerize chain reaction (PCR) amplification and their ATR-FT-IR spectra acquired. Spectra were processed to the second derivative using the Savitzky-Golay algorithm and normalized using extended multiplicative signal correction employing the UnscramblerX (CAMO, Norway) software package. Multivariate classification models and their performance were evaluated using Cohen's Kappa coefficient. Principal component analysis (PCA) score plots showed separate clusters of spectra related to membership to E. faecium and E. faecalis, with this explained by bands assigned to PO2 (1230 cm-1 ), P-O-C (1114 cm-1 ), monosubstituted alkene (997, 987 cm-1 ) and C-O (1070, 1055, 1036 cm-1 ) corresponding to teichoic acids, polysaccharides and peptidoglycan from the cell wall in PCA and PLS-DA loading plots. The best classification model for E. faecium and E. faecalis is SVM, indicating via highest Kappa score. The classification coefficient between SIMCA, PLS-DA, SVM and PCR as reference method were 0·59, 0·9 and 1, respectively, shown as the Kappa scores. CONCLUSIONS: The main spectral differences observed between the two clinically relevant enterococci species were associated with changes in the teichoic acid content of cell walls. With regard to the binary classification method, SVM was found to be the best performing classification model, providing the highest correlation with the PCR results. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that ATR-FT-IR spectroscopy in combination with chemometric modelling can be applied for the phenotypic identification and discrimination of clinically relevant and similar enterococcal species.


Subject(s)
Bacterial Typing Techniques/methods , Enterococcus/classification , Enterococcus/isolation & purification , Gram-Positive Bacterial Infections/microbiology , Spectroscopy, Fourier Transform Infrared/methods , Algorithms , Cell Wall/chemistry , Discriminant Analysis , Enterococcus/chemistry , Least-Squares Analysis , Principal Component Analysis , Support Vector Machine
10.
Poult Sci ; 99(12): 7109-7121, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33248628

ABSTRACT

Biobanking of turkey ovarian tissue appears to be the most cost-effective method for the long-term preservation of female genetics. However, to ensure the successful transplantation of biobanked ovarian tissue for breed or line revival, the transplantation and development of fresh ovarian tissue must be evaluated. To assess transplantability, ovaries from poults 1 to 15 days posthatch (dph) were cultured in ovo in chicken eggs for 6 d and compared with the equivalent fresh tissue. The viability of cultured ovarian tissue was evaluated visually, whereas the level of late-stage apoptosis was measured via the TUNEL assay. In addition, the diameter and density of prefollicular germ cells and follicles (primordial and primary) were measured to assess maturation. Results showed that all cultured grafts (74/74), on surviving chicken chorioallantoic membrane, were viable with low levels (0.8 ± 0.1%) of late-stage apoptosis. The diameter of prefollicular germ cells in cultured ovaries from poults at 5 and 7 dph were larger (P < 0.002) than that of their preculture counterparts but were not able to reach their in vivo size. No significant follicular growth was observed in ovaries cultured in ovo; however, prefollicular germ cell density was over 4-fold greater in ovaries cultured from 7 dph poults (81,030 ± 17,611/mm3) than in their in vivo counterpart (16,463 ± 6,805/mm3). Interestingly, cultured ovaries from all other ages displayed equal or lower (P ≤ 0.05) prefollicular germ cell densities than their in vivo counterparts. Cultured ovaries from poults at 5 and 7 dph also exhibited an increase (P ≤ 0.05) in follicle density compared with their preculture counterparts; whereas, cultured ovaries from 15 dph poults had decreased densities (P < 0.001) compared with their preculture counterparts. This study demonstrated that, although age of ovarian tissue cultured in ovo did not affect the overall viability, 7 dph ovaries appeared to have a better cellular morphology after culturing in ovo than other ages. In addition, we also demonstrated for the first time that avian follicles can form during tissue culturing in ovo.


Subject(s)
Biological Specimen Banks , Ovary , Ovum , Transplantation Tolerance , Turkeys , Animals , Chickens , Female , Ovarian Follicle/growth & development , Ovary/transplantation , Ovum/cytology , Ovum/metabolism , Transplantation Tolerance/physiology , Transplants/standards
11.
Anim Genet ; 51(6): 876-889, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33006154

ABSTRACT

Deviation from Mendelian inheritance expectations (transmission ratio distortion, TRD) has been observed in several species, including the mouse and humans. In this study, TRD was characterized in the turkey genome using both allelic (specific- and unspecific-parent TRD) and genotypic (additive- and dominance-TRD) parameterizations within a Bayesian framework. In this study, we evaluated TRD for 23 243 genotyped Turkeys across 56 393 autosomal SNPs. The analyses included 500 sires, 2013 dams and 11 047 offspring (trios). Three different haplotype sliding windows of 4, 10 and 20 SNPs were used across the autosomal chromosomes. Based on the genotypic parameterizations, 14 haplotypes showed additive and dominance TRD effects highlighting regions with a recessive TRD pattern. In contrast, the allelic model uncovered 12 haplotype alleles with the allelic TRD pattern which showed an underrepresentation of heterozygous offspring in addition to the absence of homozygous animals. For regions with the allelic pattern, only one particular region showed a parent-specific TRD where the penetrance was high via the dam, but low via the sire. The gene set analysis uncovered several gene ontology functional terms, Reactome pathways and several Medical Subject Headings that showed significant enrichment of genes associated with TRD. Many of these gene ontology functional terms (e.g. mitotic spindle assembly checkpoint, DRM complex and Aneuploidy), Reactome pathways (e.g. Mismatch repair) and Medical Subject Headings (e.g. Adenosine monophosphate) are known to be related to fertility, embryo development and lethality. The results of this study revealed potential novel candidate lethal haplotypes, functional terms and pathways that may enhance breeding programs in Turkeys through reducing mortality and improving reproduction rate.


Subject(s)
Genes, Lethal , Models, Genetic , Turkeys/genetics , Alleles , Animals , Bayes Theorem , Breeding , Female , Genotype , Haplotypes , Heterozygote , Inheritance Patterns , Male , Polymorphism, Single Nucleotide
12.
S Afr Med J ; 110(9): 887-893, 2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32880274

ABSTRACT

BACKGROUND: The relationship between HIV and cervical cancer is well established. Interventions that focus on creating human papillomavirus (HPV) vaccine and cervical cancer prevention messaging for adolescents, caregivers and educators will increase uptake of HPV vaccinations, HPV testing and cervical cancer screening for high-risk adolescent girls and young women (AGYW). In order to effectively develop appropriate interventions, it is important to examine AGYW's perceptions regarding their personal risk of acquiring HPV, as well as vaccine acceptability. OBJECTIVES: To measure the level of perceived personal risk of acquiring HPV and developing cervical cancer; examine the sociodemographic and behavioural factors associated with perceived risk; and assess HPV vaccine acceptability. METHODS: AGYW aged 16 - 24 years participating in the AYAZAZI study in Durban, South Africa (SA), were invited to participate in the AYA-HPV Prevention Project (AHPP), and were administered a questionnaire that assessed HPV, cervical cancer and vaccine awareness and knowledge, self-perceived HPV and cervical cancer risk, HPV vaccine uptake and acceptability, and participation in cervical cancer screening. The questionnaire measured self-perceived risk of acquiring HPV and developing cervical cancer for the respondent and other young women, as well as vaccine acceptability. Data from the main AYAZAZI study (12-month) visit were linked to AHPP substudy data. Descriptive statistics were used to analyse sociodemographic variables at the 12-month time point. Self-perceived HIV, HPV and cervical cancer risk was measured using an ordinal scale. Chi-square analyses were used to examine differences in sociodemographic and behavioural factors according to self-perceived risk of HPV and cervical cancer. RESULTS: Only a small portion of participants (14.3%) had heard of HPV. Overall, 43.0% (n=49) perceived themselves as at low HPV risk. There were significant differences in self-perceived risk of cervical cancer by age group, income and pregnancy status. The highest proportion of AGYW who perceived themselves as at high risk of cervical cancer reported being sexually active (p=0.002). Although many participants reported not knowing about HPV prior to the study, after learning about it during the study, most said that they would be willing to receive the vaccine (97.5%). CONCLUSIONS: Most young women in SA do not have access to the national HPV vaccine programme, as only girls in grade 4 in some public schools qualify. Almost all participants indicated that if the vaccine was free and recommended by a healthcare professional, they would accept it. Availability of the HPV vaccine and timely treatment of HPV infections are key issues to address in efforts to decrease cervical cancer worldwide.


Subject(s)
Health Knowledge, Attitudes, Practice , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines , Uterine Cervical Neoplasms/prevention & control , Adolescent , Adult , Age Factors , Early Detection of Cancer , Female , Humans , Income , Papillomavirus Infections/complications , Patient Acceptance of Health Care , Perception , Risk Factors , Sexual Behavior , South Africa , Surveys and Questionnaires , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Young Adult
13.
Anal Methods ; 12(35): 4334-4342, 2020 09 17.
Article in English | MEDLINE | ID: mdl-32844833

ABSTRACT

Fourier transform infrared (FTIR) spectroscopic imaging is a powerful technique for molecular imaging of pathologies associated with the nervous systems including multiple sclerosis research. However, there is no standard methodology or standardized protocol for FTIR imaging of tissue sections that maximize the ability to discriminate between the molecular, white and granular layers, which is essential in the investigation of the mechanism of demyelination process. Tissue sections are heterogeneous, complex and delicate, hence the parameters to generate high quality images in minimal time becomes essential in the modern clinical laboratory. This article presents an FTIR spectroscopic imaging study of post-mortem human brain tissue testing the effects of various measurement parameters and data analysis methods on image quality and acquisition time. Hyperspectral images acquired from the same region of a tissue using a range of the most common optical and collection parameters in different combinations were compared. These included magnification (4× and 15×), number of co-added scans (1, 4, 8, 16, 32, 64 and 128 scans) and spectral resolution (4, 8 and 16 cm-1). Images were compared in terms of acquisition time, signal-to-noise (S/N) ratio, and accuracy of the discrimination between three major tissue types in a section from the cerebellum (white matter, granular and molecular layers). In the latter case, unsupervised k-means cluster (KMC) analysis was employed to generate images from the hyperspectral images, which were compared to a reference image. The classification accuracy for tissue class discrimination was highest for the 4× magnifying objective, with 4 cm-1 spectral resolution and 128 co-added scans. The 15× magnifying objective gave the best accuracy for a spectral resolution of 4 cm-1 and 64 scans (96.3%), which was just above what was achieved using the 4× magnifying objective, with 4 cm-1 spectral resolution and 32 and 64 co-added scans (95.4 and 95.6%, respectively). These findings were correlated with a decrease in S/N ratio with increasing number of scans and was generally lower for the 15× objective. However, longer scan times were required using the 15× magnifying objective, which did not justify the very small improvement in the classification of tissue types.


Subject(s)
Brain , Hyperspectral Imaging , Brain/diagnostic imaging , Cluster Analysis , Fourier Analysis , Humans , Spectroscopy, Fourier Transform Infrared
14.
J Bacteriol ; 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32482719

ABSTRACT

The opportunistic pathogen Staphylococcus aureus is protected by a cell envelope that is crucial for viability. In addition to peptidoglycan, lipoteichoic acid (LTA) is an especially important component of the S. aureus cell envelope. LTA is an anionic polymer anchored to a glycolipid in the outer leaflet of the cell membrane. It was known that deleting the gene for UgtP, the enzyme that makes this glycolipid anchor, causes cell growth and division defects. In Bacillus subtilis, growth abnormalities from the loss of ugtP have been attributed to both the absence of the encoded protein and to the loss of its products. Here, we show that growth defects in S. aureus ugtP deletion mutants are due to the long, abnormal LTA polymer that is produced when the glycolipid anchor is missing from the outer leaflet of the membrane. Dysregulated cell growth leads to defective cell division, and these phenotypes are corrected by mutations in the LTA polymerase, ltaS, that reduce polymer length. We also show that S. aureus mutants with long LTA are sensitized to cell wall hydrolases, beta-lactam antibiotics, and compounds that target other cell envelope pathways. We conclude that control of LTA polymer length is important for S. aureus physiology and promotes survival under stressful conditions, including antibiotic stress.IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of community- and hospital-acquired infections and is responsible for a large fraction of deaths caused by antibiotic-resistant bacteria. S. aureus is surrounded by a complex cell envelope that protects it from antimicrobial compounds and other stresses. Here we show that controlling the length of an essential cell envelope polymer, lipoteichoic acid, is critical for controlling S. aureus cell size and cell envelope integrity. We also show that genes involved in LTA length regulation are required for resistance to beta-lactam antibiotics in MRSA. The proteins encoded by these genes may be targets for combination therapy with an appropriate beta-lactam.

16.
Poult Sci ; 99(5): 2746-2756, 2020 May.
Article in English | MEDLINE | ID: mdl-32359612

ABSTRACT

This study determined, for the first time, the different subpopulations of germ cells and stereological changes within the cortex of the functional left ovary during germ cell nest breakdown, and formation of the primordial follicle pool in the domestic turkey. This was accomplished by measuring the size, density, and count of prefollicular germ cells and primordial follicles in turkey poults between 1 and 35 days posthatch (dph). The percent volume (PV) of germ cells and follicles within the cortex was also calculated as a means of validating the counting technique. The total percent volume of germ cells and primordial follicles within the cortex ranged between 42 and 84%, suggesting that the counting technique was valid. Our findings show that before germ cell nest breakdown (5 dph), there were roughly 1,000,000 prefollicular germ cells within the cortex of the left ovary and that germ cell nest breakdown initiated between 5 and 7 dph, characterized by a decrease (P ≤ 0.001) in prefollicular germ cell density and the subsequent appearance of primordial follicles. Nest breakdown is followed on day 9 by the first increase (P ≤ 0.05) in size of prefollicular germ cells. These cells continue to grow throughout nest breakdown. The majority (>90%) of germ cell nest breakdowns concluded by 15 dph; although, the primordial follicle pool was not fully established until 35 dph, as determined by a total lack of prefollicular germ cells. At this point, the pool was comprised of an estimated 60,000 primordial follicles and shows that during nest breakdown and follicle pool formation, ∼94% of germ cells were lost. This 94% decrease in the number of germ cells during nest breakdown in the turkey is comparable to the domestic chicken but is greater than the average two-thirds which are lost in mammalian species.


Subject(s)
Germ Cells/physiology , Ovarian Follicle/physiology , Turkeys/physiology , Animals , Female
17.
Poult Sci ; 98(12): 6263-6269, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31407014

ABSTRACT

The objective of this study was to estimate phenotypic and genetic parameters for clutch and broodiness (BR) traits in turkeys and their relationship with body weight and egg production. Data on dam line hens was available and included: body weight at 18 wk of age (BW18), body weight at lighting (BWL, 29 to 33 wk), age at first egg (AFE), egg number (EN), rate of lay (RL), clutch length (CL), maximum clutch length (MCL), pause length (PL), maximum PL (MPL) and BR. BR was defined as the average number of consecutive pause days between clutches that was higher than the average PL per hen. Heritability estimates for BW18 and BWL were 0.50 and 0.53, respectively. The heritability for egg production, clutch, and pause traits varied from low (MPL = 0.15; BR = 0.15) to moderate (AFE = 0.22; EN = 0.28; RL = 0.29; CL = 0.21; MCL = 0.27; PL = 0.25). Genetic correlations were negative between body weight traits and EN (rg (BW18, EN) = -0.27; rg(BWL, EN) = -0.33) and CL (rg(BW18, CL) = -0.40; rg(BWL, CL) = -0.33). BR was negatively genetically correlated with EN (rg(BR, EN) = -0.85) and CL (rg(BR, CL) = -0.30), and positively genetically correlated with PL (rg(BR, PL) = 0.93) and AFE (rg(BR, AFE) = 0.21). EN had a positive (0.73) and a negative (-0.84) genetic correlation with CL and PL, respectively. Overall, the results of this study confirmed the negative (unfavorable) correlations between egg production and body weight. Despite unfavorable genetic and phenotypic correlations between egg production traits and those relating to BR, the inclusion of BR in a selection program through incorporation of clutch length traits and pause length traits is feasible. Integration of either clutch length traits or pause length traits in a selection index is likely to increase egg number while decreasing broodiness.


Subject(s)
Body Weight/genetics , Clutch Size/genetics , Nesting Behavior , Reproduction/genetics , Turkeys/physiology , Animals , Female , Turkeys/genetics
18.
J Digit Imaging ; 32(4): 597-604, 2019 08.
Article in English | MEDLINE | ID: mdl-31044392

ABSTRACT

Deep learning with convolutional neural networks (CNNs) has experienced tremendous growth in multiple healthcare applications and has been shown to have high accuracy in semantic segmentation of medical (e.g., radiology and pathology) images. However, a key barrier in the required training of CNNs is obtaining large-scale and precisely annotated imaging data. We sought to address the lack of annotated data with eye tracking technology. As a proof of principle, our hypothesis was that segmentation masks generated with the help of eye tracking (ET) would be very similar to those rendered by hand annotation (HA). Additionally, our goal was to show that a CNN trained on ET masks would be equivalent to one trained on HA masks, the latter being the current standard approach. Step 1: Screen captures of 19 publicly available radiologic images of assorted structures within various modalities were analyzed. ET and HA masks for all regions of interest (ROIs) were generated from these image datasets. Step 2: Utilizing a similar approach, ET and HA masks for 356 publicly available T1-weighted postcontrast meningioma images were generated. Three hundred six of these image + mask pairs were used to train a CNN with U-net-based architecture. The remaining 50 images were used as the independent test set. Step 1: ET and HA masks for the nonneurological images had an average Dice similarity coefficient (DSC) of 0.86 between each other. Step 2: Meningioma ET and HA masks had an average DSC of 0.85 between each other. After separate training using both approaches, the ET approach performed virtually identically to HA on the test set of 50 images. The former had an area under the curve (AUC) of 0.88, while the latter had AUC of 0.87. ET and HA predictions had trimmed mean DSCs compared to the original HA maps of 0.73 and 0.74, respectively. These trimmed DSCs between ET and HA were found to be statistically equivalent with a p value of 0.015. We have demonstrated that ET can create segmentation masks suitable for deep learning semantic segmentation. Future work will integrate ET to produce masks in a faster, more natural manner that distracts less from typical radiology clinical workflow.


Subject(s)
Deep Learning , Eye Movements/physiology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Meningeal Neoplasms/diagnostic imaging , Meningioma/diagnostic imaging , Neural Networks, Computer , Humans , Meninges/diagnostic imaging
19.
Br J Surg ; 106(4): 367-374, 2019 03.
Article in English | MEDLINE | ID: mdl-30706453

ABSTRACT

BACKGROUND: The effect of sarcopenia based on the total psoas muscle area (TPMA) on CT is inconclusive in patients undergoing abdominal aortic aneurysm (AAA) intervention. The aim of this prospective cohort study was to evaluate morphometric sarcopenia as a method of risk stratification in patients undergoing elective AAA intervention. METHODS: TPMA was measured on preintervention CT images of patients undergoing elective endovascular aneurysm repair (EVAR) or open aneurysm repair. Mortality was assessed in relation to preintervention TPMA using Cox regression analysis, with calculation of hazard ratios at 30 days, 1 year and 4 years. Postintervention morbidity was evaluated in terms of postintervention care, duration of hospital stay and 30-day readmission. Changes in TPMA on surveillance EVAR imaging were also evaluated. RESULTS: In total, 382 patient images acquired between March 2008 and December 2016 were analysed. There were no significant intraobserver and interobserver differences in measurements of TPMA. Preintervention TPMA failed to predict morbidity and mortality at all time points. The mean(s.d.) interval between preintervention and surveillance imaging was 361·3(111·2) days. A significant reduction in TPMA was observed in men on surveillance imaging after EVAR (mean reduction 0·63(1·43) cm2 per m2 ; P < 0·001). However, this was not associated with mortality (adjusted hazard ratio 1·00, 95 per cent c.i. 0·99 to 1·01; P = 0·935). CONCLUSION: TPMA is not a suitable risk stratification tool for patients undergoing effective intervention for AAA.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Computed Tomography Angiography/methods , Elective Surgical Procedures/methods , Endovascular Procedures/methods , Psoas Muscles/diagnostic imaging , Sarcopenia/diagnostic imaging , Aged , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/mortality , Cohort Studies , Elective Surgical Procedures/mortality , Endovascular Procedures/mortality , Female , Hospital Mortality/trends , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prospective Studies , Regression Analysis , Survival Analysis , Treatment Outcome
20.
Clin Oncol (R Coll Radiol) ; 31(6): 356-364, 2019 06.
Article in English | MEDLINE | ID: mdl-30737068

ABSTRACT

AIMS: Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen. MATERIALS AND METHODS: A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50-52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre. RESULTS: Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48-1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25-0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23-0.88) when compared with HRT. CONCLUSIONS: The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated.


Subject(s)
Esophageal Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Adenocarcinoma/mortality , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/mortality , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
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