Evaluating an early social communication intervention for young children with Down syndrome (ASCEND): results from a feasibility randomised control trial.

Background: This paper reports the results from a feasibility trial of an early parent-delivered social communication intervention for young children with Down syndrome ('ASCEND'). The intervention focuses on developing children's early social communication skills, in particular responding to shared attention. The aim was to inform the feasibility of running a full-scale trial through National Health Service (NHS) Speech and Language Therapy (SaLT) services, to assess whether the intervention is effective in improving language skills before children with Down syndrome start school.

Peri-anaesthetic complications in 1798 equids undergoing high-field elective orthopaedic MRI at a tertiary referral hospital.

Background: Antimicrobial prophylaxis for elective orthopaedic magnetic resonance imaging (MRI) in equids is a topic of debate among practitioners and can have negative detrimental effects on patients if used unnecessarily.

Objectives: To describe the complications with elective orthopaedic MRI of horses, mules, and donkeys under general anaesthesia without the use of peri-anaesthetic antimicrobial prophylaxis at a single large tertiary referral centre. We hypothesised that horses, mules, and donkeys undergoing general anaesthesia for elective orthopaedic MRI, without antimicrobial prophylaxis, will not be at increased risk of complications, including increased risk of infectious respiratory disease.

Breast cancer risk stratification in women of screening age: Incremental effects of adding mammographic density, polygenic risk, and a gene panel.

Purpose: There is great promise in breast cancer risk stratification to target screening and prevention. It is unclear whether adding gene panels to other risk tools improves breast cancer risk stratification and adds discriminatory benefit on a population basis.

Methods: In total, 10,025 of 57,902 women aged 46 to 73 years in the Predicting Risk of Cancer at Screening study provided DNA samples.

A systematic review of speech, language and communication interventions for children with Down syndrome from 0 to 6 years.

Background: Speech and language acquisition can be a challenge for young children with Down syndrome (DS), and while early intervention is important, we do not know what early interventions exist and how effective they may be.

Aims: To systematically review existing early speech, language and communication interventions for young children with DS from birth up to 6 years, and to investigate their effectiveness in improving speech, language and communication outcomes in children with DS. Other outcomes are changes in parental behaviour and their responsiveness METHODS & PROCEDURES: We conducted a systematic search of relevant electronic databases to identify early intervention studies targeting speech, language and communication outcomes in children with DS published up to May 2020.

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.

Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.

Suspensory ligament size does not change after plantar fasciotomy and neurectomy of the deep branch of the lateral plantar nerve by ultrasonographic assessment.

Objective: To determine the short-term effect of plantar fasciotomy and neurectomy (PFN) of the deep branch of the lateral plantar nerve on the proximal suspensory ligament (PSL) cross-sectional area (CSA) in horses with hindlimb proximal suspensory desmopathy (PSD).

Study Design: Analytical, observational, cohort study.

Sample Population: Twenty-one horses.

Ultrasound-assisted injection of the centrodistal joint in the horse.

Background: Injection of the centrodistal (CD) joint in the horse is a commonly performed procedure for both diagnostic and therapeutic purposes. This procedure can be technically challenging, and while radiographic guidance has been previously used, ultrasound localised injection of the CD joint has not been described.

Objectives: The purpose of this study was to explore the feasibility of using ultrasound localisation to increase the accuracy of CD joint injection.

What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420).

Background: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms).

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.

A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density.

Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed assess their use in a fully comprehensive model including classical risk factors, mammographic density and more than 100 SNPs associated with breast cancer. A case-control study was designed (1,668 controls, 405 cases) in women aged 47-73 years attending routine screening in Manchester UK, and enrolled in a wider study to assess methods for risk assessment. Risk from classical questionnaire risk factors was assessed using the Tyrer-Cuzick model; mean percentage visual mammographic density was scored by two independent readers.

Breast cancer pathology and stage are better predicted by risk stratification models that include mammographic density and common genetic variants.

Purpose: To improve breast cancer risk stratification to enable more targeted early detection/prevention strategies that will better balance risks and benefits of population screening programmes.

Methods: 9362 of 57,902 women in the Predicting-Risk-Of-Cancer-At-Screening (PROCAS) study who were unaffected by breast cancer at study entry and provided DNA for a polygenic risk score (PRS). The PRS was analysed alongside mammographic density (density-residual-DR) and standard risk factors (Tyrer-Cuzick-model) to assess future risk of breast cancer based on tumour stage receptor expression and pathology.

Psychological impact of providing women with personalised 10-year breast cancer risk estimates.

Background: The Predicting Risk of Cancer at Screening (PROCAS) study estimated 10-year breast cancer risk for 53,596 women attending NHS Breast Screening Programme. The present study, nested within the PROCAS study, aimed to assess the psychological impact of receiving breast cancer risk estimates, based on: (a) the Tyrer-Cuzick (T-C) algorithm including breast density or (b) T-C including breast density plus single-nucleotide polymorphisms (SNPs), versus (c) comparison women awaiting results.

Methods: A sample of 2138 women from the PROCAS study was stratified by testing groups: T-C only, T-C(+SNPs) and comparison women; and by 10-year risk estimates received: 'moderate' (5-7.

Breast cancer risk in a screening cohort of Asian and white British/Irish women from Manchester UK.

Background: The differences between breast cancer risk factors in white British/Irish and Asian women attending screening in the UK are not well documented.

Methods: Between 2009-15 ethnicity and traditional breast cancer risk factors were self-identified by a screening cohort from Greater Manchester, with follow up to 2016. Risk factors and incidence rates were compared using age-standardised statistics (European standard population).

Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk Factors for Breast Cancer Risk Prediction.

Importance: Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk prediction models.

Objective: To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density.

Design, Setting, And Participants: This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods.

Evaluation of a New Surgical Treatment for Equine Hind Limb Proximal Suspensory Desmitis.

Objective: To evaluate the effects of a new microfracture and ligament splitting procedure on ligament healing and to examine the usefulness of magnetic resonance (MR) imaging for monitoring ligament healing over time using a collagenase model of hind limb proximal suspensory desmitis.

Study Design: Experimental in vivo study.

Animals: Healthy adult horses (n=6).

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.

Introduction: The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model).

Methods: Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index.

Medical treatment of horses with deep digital flexor tendon injuries diagnosed with high-field-strength magnetic resonance imaging: 118 cases (2000-2010).

Objective: To describe the location and severity of deep digital flexor tendon (DDFT) lesions diagnosed by means of high-field-strength MRI in horses and to identify variables associated with return to activity following medical treatment.

Design: Retrospective case series.

Animals: 118 horses.

Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography.

Women from breast cancer families without a demonstrable BRCA1/2 mutation were subjected to annual mammography from age 30 years onwards. One-hundred and ninety-eight patients were diagnosed prospectively with invasive breast cancer and followed for a total of 1513 years. Overall 10-year survival was 88 %.

Comparison of limited-contact dynamic compression plate and locking compression plate constructs for proximal interphalangeal joint arthrodesis in the horse.

This study compared in vitro monotonic and cyclic mechanical properties of equine proximal interphalangeal joint arthrodeses stabilized using an open or closed technique combined with axial 4.5 mm narrow limited-contact dynamic compression plate (LC-DCP) or 4.5 mm narrow locking compression plate (LCP).

Comparison of basilar and axial sesamoidean approaches for digital flexor tendon sheath synoviocentesis and injection in horses.

Objective: To define a method for the basilar sesamoidean approach (BSA) to the digital flexor tendon sheath (DFTS) in horses and compare it with the axial sesamoidean approach (ASA) for DFTS synoviocentesis and injection.

Design: Evaluation study.

Animals: 12 healthy adult mares without evidence of abnormalities related to the lower limbs.

Response to injection of the navicular bursa with corticosteroid and hyaluronan following high-field magnetic resonance imaging in horses with signs of navicular syndrome: 101 cases (2000-2008).

Objective: To determine treatment outcome on the basis of pathological changes identified on MRI and lameness duration in horses with navicular syndrome that underwent injection of corticosteroid and hyaluronan into the navicular bursa.

Design: Retrospective case series.

Animals: 101 horses with navicular syndrome.

MRI findings in 232 horses with lameness localized to the metacarpo(tarso)phalangeal region and without a radiographic diagnosis.

Two hundred and thirty-two horses with lameness localized to the metacarpo(tarso)phalangeal (MCP/MTP) region without a radiographic diagnosis were evaluated. All horses had high-field magnetic resonance (MR) imaging of the MCP/MTP region performed for the lame limb and the contralateral limb for comparison. There were 46 horses that had bilateral abnormalities in the forelimbs; 27 of these horses were not lame in the contralateral limb at the time of examination.

Desmotomy of the accessory ligament of the deep digital flexor tendon in the forelimb of 24 horses 2 years and older.

Objective: To report outcome after desmotomy of the accessory ligament of the deep digital flexor tendon (ALDDFT) in adult horses (≥2 years) for treatment of desmitis of the ALDDFT or flexural deformity of the distal interphalangeal joint (FDDIJ).

Study Design: Case series.

Animals: Horses with desmitis of the ALDDFT (n=9) and FDDIJ (n=15).

Evaluation of an arthroscopic approach for transection of the equine collateral sesamoidean ligament.

Objective: To evaluate: (1) an arthroscopic technique for transection of the collateral sesamoidean ligament (CSL); and (2) the healing response using magnetic resonance (MR) and microscopic examination.

Study Design: Experimental study.

Animals: Adult horses (n=6).

Magnetic resonance imaging findings in horses with recent onset navicular syndrome but without radiographic abnormalities.

Seventy-two horses with recent onset of navicular syndrome and normal radiographs were assessed. Horses underwent magnetic resonance (MR) imaging of both front feet. All abnormalities were characterized and the most severe abnormality identified, if possible.