The Haemato-Oncology Frailty (HOF) score to assess frailty in lymphoma.

Morbidity and mortality during chemotherapy in older adults with haematological malignancy can be unpredictable. The Haemato-Oncology Frailty (HOF) score was previously found to predict outcomes in a cohort of patients with plasma cell myeloma. In this study, we assess its utility in assessing frailty in patients with lymphoma, and compare its performance to that of two other frailty scores. The HOF score was able to predict progression-free survival in this population, and was also shown to have potential in assessing the dynamism of frailty during chemotherapy. It performed well when compared to the Charlson Comorbidity Index (CCI) score and the Haematopoietic Cell Transplantation-Specific Comorbidity Index (HCTCI), although the study was not powered to assess for non-inferiority. The HOF score is a new score with the potential for application in different haematological malignancies.

Copper Levels in Patients with Unexplained Dysplastic Cytopenia.

Copper deficiency can produce changes mimicking myelodysplasia, but its prevalence among haematology patients is unknown. This study evaluates the prevalence of deficiency in a population of patients with unexplained cytopenia(s) and dysplasia. Of 17 patients recruited, only one was found to have a low copper level. This is the first study evaluating hypocupremia in patients with isolated haematological manifestations. Our results suggest that copper deficiency is uncommon in this population, and the routine measurement of copper seems unlikely to be cost-effective. We recommend a risk-assessed approach to testing based on the identification of risk factors and of signs suggestive of deficiency.

Non-malignant CSF lymphocytosis in a patient with acute lymphoblastic leukemia.

Patients with haematological malignancy are often profoundly immune suppressed, and more so if they require more than one line of therapy. Infection should always be considered when they become unwell. We discuss the differential diagnoses of a young man with multiply-relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia who presented with neurological symptoms and cerebrospinal fluid lymphocytosis. The diagnostic approach needs to be rapid and structured, and may require microbiology and neurology support.

Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding.

Flow cytometry and thromboelastography to assess platelet counts and coagulation in patients with haematological malignancies.

BACKGROUND: Accurate platelet counts (PC) are necessary in order to follow recommendations for prophylactic platelet transfusion. We carried out a study comparing the standard way of counting platelets using a routine analyser and compared it with PC determined by flow cytometry (FC) and haemostatic data obtained with thromboelastography (TEG). MATERIALS AND METHODS: The study was carried out on 24 patients with haematological malignancies, all given one adult dose of platelets. The PC was determined before and after transfusion using an automated blood cell counter and FC. Citrated, "native" whole blood TEG was carried out before and after platelet transfusion to assess global haemostasis. RESULTS: No bleeding was observed in any of the subjects. Thirty-one assessments were performed in the 24 patients. The mean pre-transfusion PC were 9.8 and 13×10(9)/L with the automated counter and FC, respectively with a difference of 3.7 (p=0.0011). Excellent correlation was observed between the two counts (r=0.89; p<0.0001). Mean post-transfusion increments were 23 and 29×10(9)/L for the routine counter and FC, respectively. Using the immunological PC, patients would not have qualified for transfusion in 18.2% of cases since their PC was >20×10(9)/L. TEG showed a shortened reaction time in 69.6% of cases and a normal mean K time of 6.7 min. Only 9% had a low α angle signifying hypocoagulability. The maximum amplitude was reduced in the majority of cases but normal in 25% despite PC<20×10(9)/L. Mean activated partial thromboplastin time, prothrombin time and fibrinogen were normal prior to transfusion. DISCUSSION: Although higher PC as assessed by FC could potentially have an impact on platelet transfusion practices, TEG was sensitive enough to detect PC<10×10(9)/L and some between 10-20×10(9)/L. Whether patients with the latter PC are more prone to bleeding remains to be verified in larger studies.

Population models of genomic imprinting. II. Maternal and fertility selection.

Under several hypotheses for the evolutionary origin of imprinting, genes with maternal and reproductive effects are more likely to be imprinted. We thus investigate the effect of genomic imprinting in single-locus diallelic models of maternal and fertility selection. First, the model proposed by Gavrilets for maternal selection is expanded to include the effects of genomic imprinting. This augmented model exhibits novel behavior for a single-locus model: long-period cycling between a pair of Hopf bifurcations, as well as two-cycling between conjoined pitchfork bifurcations. We also examine several special cases: complete inactivation of one allele and when the maternal and viability selection parameters are independent. Second, we extend the standard model of fertility selection to include the effects of imprinting. Imprinting destroys the "sex-symmetry" property of the standard model, dramatically increasing the number of degrees of freedom of the selection parameter set. Cycling in all these models is rare in parameter space.