JAHK: a low frequency antigen associated with the rG complex of the Rh blood group system

We have investigated a 'new' low frequency antigen JAHK, which is a marker for the rare Rh gene complex rG. The rG haplotype does not produce any D, c or E antigens, but does produce a strong G antigen. The rG haplotype [d(C)(e)G] is associated with weak C and weak e antigens. Three unrelated rG/dce individuals and one rG/rG propositus were JAHK+. In addition, three propositi whose red cells had a typical expression of C and/or e antigen, which could not be shown to be rG because of a normal D antigen produced by the haplotype in trans, were also JAHK+. Families of three of the propositi demonstrate the inheritance of JAHK as a Mendelian dominant character. It is likely that the JAHK antigen results from conformational changes in an RhCcEe protein that has the amino acid characteristic of c antigen at position 16 and the amino acid residues characteristic of C antigen at positions 60, 68, and 103. JAHK has been assigned the number RH53.     

Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms

Mitchell PB, Johnston AK, Frankland A, Slade T, Green MJ, Roberts G, Wright A, Corry J, Hadzi‐Pavlovic D. Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms. Objective: The World Mental Health Version of the Composite International Diagnostic Interview (WMH‐CIDI) DSM‐IV bipolar disorder diagnostic algorithms were recalibrated in about 2006 following evidence of over‐diagnosis of bipolar I disorder. There have been no reports of the impact of this recalibration on epidemiological findings. Method: Data were taken from the 2007 Australian National Survey of Mental Health and Wellbeing. Findings for cases identified by the recalibrated bipolar disorder definition were contrasted against those identified by the un‐recalibrated definition. Results: The 12‐month prevalence of recalibrated bipolar disorder and un‐recalibrated bipolar disorder were 0.9% and 1.7% respectively. The un‐recalibrated bipolar disorder group was younger and more likely to have never married than the recalibrated bipolar disorder group. They were also more likely to have a comorbid alcohol use disorder, substance use disorder and asthma or arthritis. While they were more likely to have at least severe interference in at least one of the Sheehan Scale domains of functioning, they were less likely to have made a suicide attempt. Similarly, they were less likely to have consulted a psychiatrist. Conclusion: It is not possible to be certain about the nature of these differences. Some may be artifactual (reflecting greater statistical power to detect differences with the larger un‐recalibrated bipolar disorder defined sample), while others may be indicative of the inclusion of a clinically distinct subpopulation with the un‐recalibrated bipolar disorder definition, thereby producing a more heterogeneous sample. These findings indicate the need for clarity in the diagnostic algorithm used in epidemiological reports on bipolar disorder using the World Mental Health Version of the Composite International Diagnostic Interview.     

The maximal sniff in the assessment of diaphragm function in man

We studied diaphragm function in a total of 64 normal subjects, who had no past or present respiratory or neuromuscular impairment. We measured transdiaphragmatic pressure (Pdi) during maximal sniffs and compared these values with Pdi during maximal static inspiratory efforts (PImax.). The range of Pdi during maximal sniffs (82-204 cm H2O) had better defined lower limits than Pdi during PImax. (16-164 cm H2O) and a higher mean value: mean +/- SD for maximal sniffs was 137 +/- 28 cm H2O and for PImax. was 90 +/- 37 cm H2O. The reproducibility of sniff Pdi was assessed in eight randomly chosen subjects over 3 days: the mean coefficient of variation was 7.2%. By comparison the coefficient of variation of Pdi during PImax. was 13.0% in seven subjects. The maximal sniff is a spontaneous manoeuvre, easily performed, repeatable without tiring, and reproducible. Its measurement provides a more reliable quantitative method for assessment of diaphragm strength, which has potential in clinical practice.     

Hb Leeds [beta56(D7)Gly-->Cys]: a new hemoglobin that aggravates anemia in a child with beta(0)-thalassemia trait

A novel beta chain variant found in combination with beta(0)-thalassemia (thal) was identified in a male infant by electrospray ionization mass spectrometry (ESI-MS). Analysis of the infant's denatured blood and a 30 min. tryptic digest of his blood identified the mutation as beta56(D7)Gly-->Cys, which was confirmed by tandem mass spectrometry (MS/MS). We have named this new variant Hb Leeds. The infant's parents, resident in Yorkshire, UK, but originally from Pakistan, were found to have beta(0)-thalassemia (thal) trait (mother) and Hb Leeds trait (father). Hematological data on the infant's parents and siblings are given. Hb Leeds trait was also found in three unrelated Pakistani adults living in the same area of Yorkshire. Hb Leeds trait in adults appears to have few clinical manifestations, but when combined with beta(0)-thal it led to a more severe anemia in the infant than in the corresponding thalassemic trait in his mother.     

Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank

Background Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions.Methods Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within 2 years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer.Results A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase = 2.12 [1.86–2.41] P = 3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739–0.796]). Prostate cancer incidence was 8.1% (6.7–9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was <1%.Conclusions This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care.Subject terms: Risk factors, Diagnostic markers, Cancer genomics, Prostate cancer, Diagnosis