Identification of candidate novel production variants on the Bos taurus chromosome X.

Chromosome X is often excluded from bovine genetic studies due to complications caused by the sex specific nature of the chromosome. As chromosome X is the second largest cattle chromosome and makes up approximately 6% of the female genome, finding ways to include chromosome X in dairy genetic studies is important. Using female animals and treating chromosome X as an autosome, we performed X chromosome inclusive genome-wide association studies in the selective breeding environment of the New Zealand dairy industry, aiming to identify chromosome X variants associated with milk production traits. We report on the findings of these genome-wide association studies and their potential effect within the dairy industry. We identify missense mutations in the MOSPD1 and CCDC160 genes that are associated with decreased milk volume and protein production and increased fat production. Both of these mutations are exonic SNP that are more prevalent in the Jersey breed than in Holstein-Friesians. Of the 2 candidates proposed it is likely that only one is causal, though we have not been able to identify which is more likely.

Cutaneous toxicities in patients with melanoma receiving checkpoint inhibitor therapy: a retrospective review. The experience of a single large specialist institution.

Checkpoint inhibitor (CPI) therapy has significantly improved overall survival for metastatic melanoma, and is now approved for use in the adjuvant setting. Modulating the immune system is recognized to cause cutaneous immune-related adverse events (irAEs). We conducted a retrospective observational cohort study of adult patients with melanoma at our tertiary referral centre, who received CPI therapy from 2006 to March 2018. This is the single largest study of cutaneous irAEs occurring on CPI therapy in patients with melanoma to date and encompasses 12 years. The results showed that cutaneous toxicity occurs in 24% of patients but is generally manageable, with < 5% patients discontinuing treatment.

Short communication: Identification of the pseudoautosomal region in the Hereford bovine reference genome assembly ARS-UCD1.2.

In cattle, the X chromosome accounts for approximately 3 and 6% of the genome in bulls and cows, respectively. In spite of the large size of this chromosome, very few studies report analysis of the X chromosome in genome-wide association studies and genomic selection. This lack of genetic interrogation is likely due to the complexities of undertaking these studies given the hemizygous state of some, but not all, of the X chromosome in males. The first step in facilitating analysis of this gene-rich chromosome is to accurately identify coordinates for the pseudoautosomal boundary (PAB) to split the chromosome into a region that may be treated as autosomal sequence (pseudoautosomal region) and a region that requires more complex statistical models. With the recent release of ARS-UCD1.2, a more complete and accurate assembly of the cattle genome than was previously available, it is timely to fine map the PAB for the first time. Here we report the use of SNP chip genotypes, short-read sequences, and long-read sequences to fine map the PAB (X chromosome:133,300,518) and simultaneously determine the neighboring regions of reduced homology and true pseudoautosomal region. These results greatly facilitate the inclusion of the X chromosome in genome-wide association studies, genomic selection, and other genetic analysis undertaken on this reference genome.

The UK guidelines for management and surveillance of Tuberous Sclerosis Complex.

BACKGROUND: The severity of Tuberous Sclerosis Complex (TSC) can vary among affected individuals. Complications of TSC can be life threatening, with significant impact on patients' quality of life. Management may vary dependent on treating physician, local and national policies, and funding. There are no current UK guidelines. We conducted a Delphi consensus process to reach agreed guidance for the management of patients with TSC in the UK. METHODS: We performed a literature search and reviewed the 2012/13 international guideline for TSC management. Based on these, a Delphi questionnaire was formed. We invited 86 clinicians and medical researchers to complete an online survey in two rounds. All the people surveyed were based in the UK. Clinicians were identified through the regional TSC clinics, and researchers were identified through publications. In round one, 55 questions were asked. In round two, 18 questions were asked in order to obtain consensus on the outstanding points that had been contentious in round one. The data was analysed by a core committee and subcommittees, which consisted of UK experts in different aspects of TSC. The Tuberous Sclerosis Association was consulted. RESULTS: About 51 TSC experts took part in this survey. Two rounds were required to achieve consensus. The responders were neurologists, nephrologists, psychiatrist, psychologists, oncologists, general paediatricians, dermatologist, urologists, radiologists, clinical geneticists, neurosurgeons, respiratory and neurodisability clinicians. CONCLUSIONS: These new UK guidelines for the management and surveillance of TSC patients provide consensus guidance for delivery of best clinical care to individuals with TSC in the UK.

Laser treatment for female facial hirsutism: are quality-of-life benefits sustainable?

BACKGROUND: Facial hirsutism in women impairs quality of life (QoL). Laser hair removal (LHR) has been shown to confer significant improvements in QoL for up to 6 months after treatment, but the longer-term benefits have not been investigated. AIM: To assess the sustainability of LHR benefits to the QoL of hirsute women up to 30 months after treatment. METHODS: Hirsute women about to undergo National Health Service (NHS)-funded LHR in 2010-2012 (n = 142) completed proforma questionnaires quantifying the burden of hirsutism on their QoL. These included: the Dermatology Life Quality Index (DLQI) (assessing functional impact on QoL), the number of days spent removing hair per week and a 10-point scale assessing how much their condition bothered them (emotional burden on QoL). Postal questionnaires recorded QoL changes up to 30 months after LHR. Improvements in QoL scores for each woman were compared. Responses were then grouped into periods of 0-6, 6-12 and 12-30 months post-treatment, and the magnitude of change between these time groups was compared for each QoL measure. RESULTS: In total, 63 women responded to the post-LHR questionnaire. QoL was severely affected, but improved with LHR. The number of days spent removing hair reverted to baseline at 12-30 months post-LHR, and a significant decline was seen in the magnitude of improvement in emotional burden on QoL over time (P = 0.04). However, no significant difference existed between improvements in DLQI scores (P = 0.12). CONCLUSION: LHR supplies some functional QoL benefits up to 30 months post-treatment. Emotional benefits are less sustainable. Further LHR treatment is required to maintain QoL benefits.

Calcific panniculitis in adult-onset dermatomyositis.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with characteristic cutaneous features. Panniculitis is a rarely reported clinical finding in this condition. This report describes two cases of adult-onset DM complicated by severe calcific panniculitis. In both cases, the associated pain and loss of function seemed to be best managed on combination anti-malarial therapy with mepacrine and hydroxychloroquine.

Treatment with carbon dioxide laser of painful skin metastases from a laryngeal neuroendocrine carcinoma.

An 82-year-old man presented with multiple, exquisitely painful skin metastases from an atypical carcinoid tumour of the larynx. These were treated successfully with carbon dioxide laser. To our knowledge, this is the first reported case of laser treatment used in the management of neuroendocrine skin metastases.

Potassium titanyl phosphate (KTP) laser treatment for molluscum contagiosum.

We report a case of an immunocompromised 38-year-old Asian patient who developed several hundred atypical lesions of molluscum on her face and neck, resistant to conventional treatment. These lesions were treated successfully by potassium titanyl phosphate (KTP) laser without pigmentary disturbance. KTP laser is a novel treatment for molluscum contagiosum.

High-resolution ultrasound reflex transmission imaging and digital photography: potential tools for the quantitative assessment of pigmented lesions.

BACKGROUND/AIMS: High-resolution ultrasound (HRU) is a relatively cheap imaging method that shows small quantitative differences between benign naevi and melanoma. Previous studies using B-mode display suggest that these arise from their differing attenuating properties. Attenuation characteristics, however, are better evaluated using reflex transmission imaging (RTI). White light clinical (WLC) photography is an even cheaper imaging method that is routinely used for monitoring but less frequently in everyday diagnosis. As features from each method may have an independent origin, two such modalities may be of greater diagnostic value than either method alone. However, although quantitative analysis of digital photographs is being developed to aid tumour diagnosis, in vivo RTI for the evaluation of pigmented skin lesions has not previously been described. This paper presents the feasibility of performing RTI in vivo and evaluates the reliability of the objective features used. The potential of the combination of quantitative RTI and white light (WL) digital photography data for the classification of pigmented lesions was assessed. METHODS: Randomly selected patients were recruited via a skin cancer screening clinic. RTI data were acquired from each index lesion with a 20 MHz single-element scanner. WL images were taken using a high-resolution (2.8 Mpixels) digital camera. Quantitative features calculated from both images were used to derive a discriminant rule. This equation was then applied to reclassify each case based on its quantitative criteria. The resultant classification was compared with histological diagnosis. RESULTS: Twenty-four lesions (10 melanoma and 14 naevi) were studied. On RTI, no subjective differences were observed between benign naevi and melanoma. Many lesions were either not visible on RTI or lacked clearly definable borders. Consequently, the WL photographs were used to draw lesion boundaries on RT images for feature calculation. Melanoma were less attenuating than naevi on RTI (P=0.026) and had greater red colour variegation on WL imaging (P=0.016). The combination of quantitative parameters (two from RTI and four from photographs) improved sensitivity for this sample without compromising the specificity of 100% compared with either modality alone. The procedure is highly reproducible (r=0.85 between two operators). CONCLUSIONS: Pigmented skin lesions can be quantitatively defined from RTI data acquired in vivo and a significant difference in attenuation is shown. However, accurate registration of the RT image with a corresponding photograph was crucial for this purpose and only possible when corresponding points could be reliably identified on both images. Combination of features from ultrasound and optical images may synergistically improve diagnostic accuracy and a larger study is warranted to investigate this.

A compact electric potential sensor array for the acquisition and reconstruction of the 7-lead electrocardiogram without electrical charge contact with the skin.

Conventional electrocardiogram (ECG) systems make use of separate electrical connections to the arms and legs. These use a 'long baseline' for the voltage reference potential which in the case of precordial ECG leads is provided using a Wilson central terminal (WCT) wiring configuration. The aims of this project were (a) to construct compact, non-invasive surface ECG sensor arrays which would operate without the need for a WCT reference, (b) to obtain high quality precordial ECGs showing fine differences in ECG detail between small adjacent areas of the chest and (c) to reconstruct, from a compact array of four sensors, ECGs which closely match to the conventional 7-lead ECG system, but without the need for multiple wires and long baselines. In this paper, we describe two sensor array configurations which have been constructed using electric potential sensors (EPSs). We show high quality precordial ECGs obtained from small areas of the surface of the chest and show the different angular vectors (leads) in the frontal cardiac plane constructed using signals from the array elements. We suggest that these ECG arrays, which are simple to apply, should prove to be a valuable tool in providing useful information about the state of the heart.