Reduced-order parameter optimization for simplifying prostate IMRT planning

Intensity-modulated radiotherapy (IMRT) has become an effective tool for cancer treatment with radiation. However, even expert radiation planners still need to spend a substantial amount of time manually adjusting IMRT optimization parameters such as dose limits and costlet weights in order to obtain a clinically acceptable plan. In this paper, we describe two main advances that simplify the parameter adjustment process for five-field prostate IMRT planning. First, we report the results of a sensitivity analysis that quantifies the effect of each hand-tunable parameter of the IMRT cost function on each clinical objective and the overall quality of the resulting plan. Second, we show that a recursive random search over the six most sensitive parameters as an outer loop in IMRT planning can quickly and automatically determine parameters for the cost function that lead to a plan meeting the clinical requirements. Our experiments on a ten-patient dataset show that for 70% of the cases, we can automatically determine a plan in 10 min (on the average) that is either clinically acceptable or requires only minor adjustment by the planner. The outer-loop optimization can be easily integrated into a traditional IMRT planning system.     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.     

兔耳病理性瘢痕皮回植术后组织中基质金属蛋白酶－1及金属蛋白酶组织抑制剂－1表达的变化

目的通过建立兔耳模型观察基质金属蛋白酶－1（matrixmetalloproteinase－1,MMP－1）及金属蛋白酶组织抑制剂－1（tissueinh｜bitorofmetalloproteinase1,TIMP1）在病理性瘢痕皮回植术后组织中表达的变化,探讨瘢痕皮回植治疗病理性瘢痕的机制。方法建立兔耳病理性瘢痕模型。共分为3组：正常皮肤组（对照组,A组）、病理性瘢痕组（B组）及瘢痕皮回植组（c组）。切取标本行HE染色和Masson特殊组织化学染色及免疫组织化学染色,观察各组标本MMP－1、TIMP－1的表达情况。结果病理性瘢痕经瘢痕皮回植术后,MMP－1及TIMP－l均较A组明显升高（P〈O．01）．MMP一1的表达较TIMP一1明显增强（P〈O．01）。结论瘢痕皮回植术治疗瘢痕的机制与瘢痕组织内MMP一1和TIMP一1相互作用的失衡有关。     

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.     

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Peripheral blood mononuclear cells from pregnant and postpartum women were cultured in vitro with erythropoietin. Burst-forming unit (BFU-E)-derived erythroid colonies composed of immature erythroblasts with low hemoglobin contents were observed by day 8 of culture. By day 12 of culture, numerous BFU-E-derived erythroid colonies with high hemoglobin contents were present. The gamma/(gamma + beta) globin synthetic ratio was approximately 12% in the early cultures and 6% in the late cultures, indicating that the proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. These studies also reveal that the capacity fof fetal hemoglobin production by peripheral blood BFU-E in vitro is not altered during pregnancy.     

Human embryonic zeta-globin chain expression in deletional alpha-thalassemias.

zeta-Globin chain expression in carriers of a number of deletional alpha-thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (--SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (--MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia.     

Baseline Socio-demographic Characteristics and Self-Reported Diet and Physical Activity Shifts Among Recent Immigrants Participating in the Randomized Controlled Lifestyle Intervention: “Live Well”

The goal of this paper is to describe the baseline characteristics of Live Well (intervention to prevent weight gain in recent immigrant mother–child dyads from Brazil, Haiti, and Latin America) participants, and to explore self-reported changes in diet and physical activity post-immigration. Baseline data from 383 mothers were used for this study. Dyads attended a measurement day where they completed self-administered surveys collecting information about socio-demographics, diet, physical activity, other psychosocial variables, and height and weight. Haitian mothers’ socio-demographic profile differed significantly from that of Brazilians’ and Latinas’: they have been in the US for a shorter period of time, have higher rates of unemployment, are less likely to be married, more likely to have ≥3 children, more likely to be obese, and have immigrated for family or other reasons. In multivariate models, self-reported changes in diet and physical activity since migrating to the US were significantly associated with BMI with non-linear relationships identified. Future research is needed to understand how diet and physical activity change while acculturating to the US and explore the adoption of both healthy and unhealthy dietary changes.