Derived Reference Values Research Articles

Establishing Reference Values in the Neuromuscular Ultrasound Laboratory Using the e-Norms Method: A Feasibility Study.

The standard procedure to establish reference values in a neuromuscular laboratory involves examining healthy controls, as nerve size varies with the population and muscle echo intensity (EI) is device-specific. We aimed to derive these reference values by extrapolation from a studied sample (the e-norms method), compare them with published reference values, and determine their diagnostic accuracy. We retrospectively analyzed data from consecutive patients who underwent nerve and/or muscle ultrasound in our ultrasound laboratory, which is a tertiary referral center for neuromuscular diseases in Southern Poland in the years 2018-2023. We plotted the cross-sectional area (CSA) of the nerve segments and EI of the individual muscles and derived descriptive statistics from the plateau of the e-norms curve. We compared the mean difference of the nerve size to other studies and determined the ability of the muscle EI to discriminate myopathic versus healthy subjects using receiver operator characteristics curves. We analyzed 1124 nerves and 1154 muscles from 109 and 99 subjects, respectively. The derived reference values for nerve CSA were mostly concordant with other studies, including all nerve segments in the legs and with the exception of compression sites and the most proximal nerve segments in the arms. Using the reference values for muscle EI established with the e-norms method, we were able to discriminate myopathic from healthy subjects with 85% sensitivity and 92% specificity. The e-norms is a feasible method to establish reference values in the neuromuscular ultrasound laboratory.

Functional Capacity Profile of the Cervical Joint in Young Adults: Sex-Related Differences

The functional capacity of the cervical spine plays a central role in healthy living. The aim of this study was to examine the sex-related effect on cervical strength, range of motion (ROM), and the musculoskeletal pain profile in young physically active individuals. A total of 30 males and 30 females (21.53 ± 1.15 years old), without injury or chronic pain at the cervical joint, participated in the study. ROM (forward flexion, extension, lateral flexion-rotation), maximal isometric strength (forward flexion, extension, lateral flexion), and musculoskeletal pain were assessed using an electronic goniometer, a handheld dynamometer, and the Nordic questionnaire, respectively. The results revealed that: (a) females had higher ROM during extension and lateral flexion than males (p < 0.05); (b) males had higher absolute strength than females in all movement directions, and higher relative strength/body mass (at forward flexion) and flexion/extension ratio (p < 0.05); (c) ROM and strength were not significantly different between right and left sides (p > 0.05); (d) a large proportion (43.3%) of the participants had cervical pain; and (e) cervical strength showed a significant small negative correlation with pains (p < 0.05; r = −0.225 to −0.345). In conclusion, the derived reference values may be used by health and fitness professionals to extensively evaluate the cervical spine and to design specific exercise programs for injury prevention and rehabilitation.

Biventricular Tissue Tracking with Cardiovascular Magnetic Resonance: Reference Values of Left- and Right-Ventricular Strain.

We derived reference values of left-ventricular (LV) and right-ventricular (RV) strain parameters in a cohort of 100 healthy subjects by feature tracking cardiac magnetic resonance (FT-CMR). Global and regional strain values were calculated for the LV; circumferential and radialSAX strain parameters were derived from the short-axis (SAX) stack, while longitudinal and radialLAX strain parameters were assessed in three long-axis (LAX) views. Only global longitudinal strain (GLS) was calculated for the RV. Peak global LV circumferential strain was -16.7% ± 2.1%, LV radialSAX strain was 26.4% ± 5.1%, LV radialLAX strain was 31.1% ± 5.2%, LV GLS was -17.7% ± 1.9%, and RV GLS was -23.9% ± 4.1%. Women presented higher global LV and RV strain values than men; all strain values presented a weak relationship with body surface area, while there was no association with age or heart rate. A significant association was detected between all LV global strain measures and LV ejection fraction, while RV GLS was correlated to RV end-diastolic volume. The intra- and inter-operator reproducibility was good for all global strain measures. In the regional analysis, circumferential and radial strain values resulted higher at the apical level, while longitudinal strain values were higher at the basal level. The assessment of cardiac deformation by FT-CMR is feasible and reproducible and gender-specific reference values should be used.

Heart rate-corrected systolic ejection time: population-based reference values and differential prognostic utility in acute heart failure.

Systolic ejection time (SET) is discussed as a treatment target in patients with heart failure (HF) and a reduced left ventricular (LV) ejection fraction (EF). We derived reference values for SET correcting for its dependence on heart rate (SETc), and explored its prognostic utility in patients admitted with decompensated HF. SETc was derived in 4836 participants of the population-based STAAB study (mean age 55 ± 12 years, 52% women). There, mean SETc was 328 ± 18 ms, increased with age (+4.7 ms per decade), was shorter in men than women (-14.9 ms), and correlated with arterial elastance (r = 0.30; all P < 0.001). In 134 patients hospitalized with acute HF, SETc at admission was shorter when compared with the general population and differed between patients with HF with reduced EF (HFrEF; LVEF ≤40%; 269 ± 35 ms), HF with mildly reduced EF (HFmrEF; LVEF 41-49%; 294 ± 27 ms), and HF with preserved EF (HFpEF; LVEF ≥50%; 317 ± 35 ms; P < 0.001). In proportional hazard regression, an in-hospital increase in SETc was associated with an age- and sex-adjusted hazard ratio of 0.38 (95% confidence interval 0.18-0.79) in patients with HFrEF, but a hazard ratio of 2.39 (95% confidence interval 1.24-4.64) in patients with HFpEF. In the general population, SETc increased with age and an elevated afterload. SETc was mildly reduced in patients hospitalized with HFpEF, but markedly reduced in patients with HFrEF. In-hospital prolongation of SETc predicted a favourable outcome in HFrEF, but an adverse outcome in HFpEF. Our results support the concept of a U-shaped relationship between cardiac systolic function and risk, providing a rationale for a more individualized treatment approach in patients with HF.

Cardiovascular magnetic resonance derived biventricular strain in healthy adolescents: reference values and comparison between myocardial tagging and feature-tracking

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III (ISCIII) European Regional Development Fun/European Social Fund (A way to make Europe/Investing in your future). Background Strain measurements have demonstrated to be earlier and more sensitive markers of contractile dysfunction than ejection fraction (EF) alone. Myocardial tagging (MT) is considered the reference standard for CMR strain measurements, but its clinical application is limited because acquisition and analysis are laborious and time consuming. Feature-tracking (FT) CMR allows strain quantification using steady-state in free-precession (SSFP) sequence, which is obtained in routine CMR protocols, being easily applicable in clinical practice. Literature regarding reference strain values in pediatric populations is scarce and, to the best of our knowledge, there are no studies comparing FT and MT in healthy adolescents. Purpose To provide CMR strain reference values in healthy adolescents and compare FT to MT results. Methods A CMR study was performed in healthy adolescents enrolled in the "Early ImaginG Markers of unhealthy lifestyles in Adolescents" (EnIGMA) project using a 3-Tesla CMR scanner between March and October 2021. The imaging protocol included a cine SSFP to provide images for chamber size and function, including FT; and MT acquisitions using spatial modulation of magnetization (SPAMM) technique. Cine acquisitions included the entire left ventricular (LV) short axis and long-axis 4 chamber (4c)- and 2 chamber (2c)-views, while MT acquisitions included three short axis slices (basal, mid and apical) and long-axis 4c-view. Endo- and epicardial borders were manually contoured in the end-diastolic (ED) phase. A non-rigid, elastic algorithm was used for segmentation and registration for strain quantification. If tracking was suboptimal, the software only allowed adaptations of the contours on the ED image. Longitudinal (LS) and circumferential (CS) strains were obtained for the LV and right ventricle (RV). Results CMR scans were performed in 123 adolescents (64 girls, 52.0%) with a mean age of 16.0 years (standard deviation [SD]=0.4), a mean LVEF of 62.5% (SD=4.1) and a mean RVEF of 56.2% (SD=4.6). Reference percentiles (P) 3, 10, 25, 50, 90 and 97 for strain values by sex are provided in Figure 1. FT-measured LVLS and LVCS were higher in girls than in boys (-19.8 vs -17.8%, p&amp;lt;0.01; and -22.2 vs -21.0%, p&amp;lt;0.01; respectively), and these differences were confirmed with MT analysis. There were no consistent between-sex differences for RVLS and RVCS. Bland-Altman analyses showed reasonable agreement between FT and MT for LVLS, LVCS, RVLS and RVCS (Figure 2 A, B, C and D). Conclusions This study provided CMR derived reference values for left and right ventricle strain in adolescents aged 15 to 18 years. This work suggests that FT is a reasonably valid technique to measure LV and RV strain in this population. This information may be useful for diagnostic and prognostic implications in adolescent patients.

Female-specific reference values for blood pressure and its relationship with subclinical echocardiographic findings in women with a history of preeclampsia: the Queen of Hearts study

Abstract Introduction Hypertension is the most crucial modifiable risk factor for cardiovascular disease (CVD). Sex differences in what is considered optimal blood pressure (BP) might deviate from current sex-blinded guidelines for hypertension. In women, an obstetric history of preeclampsia relates to postpartum hypertension and substantially increases the risk of premature CVD. Purpose To establish female-specific reference values for BP in relatively young women and assess its association with subclinical aberrant echocardiographic findings in a high-risk female population. Methods Data was used from the Queen of Hearts study; a cross-sectional cohort study on early detection of heart failure among young women with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancy. The control group was used to non-parametrically establish reference values for BP (95th percentile). The association between the derived reference values and the risk of subclinical aberrant echocardiographic findings was evaluated in the former preeclamptic group using logistic regression. All women were admitted to a standardized cardiovascular assessment including transthoracic echocardiography and 30-minutes BP measurement. Subclinical echocardiographic findings included left ventricular (LV) hypertrophy (LVH), LV concentric remodelling (LCVR), diastolic dysfunction (DD) and impaired LV ejection fraction (LVEF, &amp;lt;55%). Results A total of 429 women in the healthy control group and 856 in the former preeclamptic group were included (44±8 and 38±8 years, respectively). In the healthy control group, 97.7% and 99.8% of women had a systolic (SBP) and diastolic BP (DBP) value below the European Society of Cardiology (ESC) guidelines for hypertension. Overall, the derived reference value for SBP and DBP in our control group was 133 and 82 mmHg, respectively. Age-specific reference curves are presented in Figure 1 and 2. In the subgroup of former preeclamptic women 10.4% and 14.6% had SBP and DBP levels above 133 mmHg and 82mmHg, respectively. In this group, the Odds Ratio (OR) for subclinical aberrant echocardiographic findings when having SBP ≥133mmHg was 5.3 (95% CI 2.3–12.3) for LVH, 1.4 (95% CI 0.6–3.2) for LVCR, 5.9 (95% CI 3.3–10.7) for DD and 1.3 (95% CI 0.3–6.0) for impaired LVEF. For DBP ≥82mmHg, the OR for LVH was 3.5 (95% CI 1.5–8.0), LVCR 1.3 (95% CI 0.6–2.7), DD 3.4 (95% CI 1.9–6.0) and impaired LVEF 1.5 (95% CI 0.4–5.3). Conclusions Upper limits for SBP and DBP values in current guidelines correspond with the value of less than 2% of women in our healthy (no pre-eclampsia) population. We derived new reference values with the upper limit corresponding with the upper 5th centile. Values above this level, even below decision limits for hypertension, are associated with abnormal subclinical cardiac function and geometry in a high-risk young female population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation

Cardiac magnetic resonance imaging derived reference values for ventricular anatomy and function and myocardial tissue characterization in adolescents: the EnIGMA study

Abstract Introduction Cardiac magnetic resonance (CMR) imaging is a precise tool for the assessment of cardiac anatomy and function. However, studies providing reference values for CMR parameters, including myocardial tissue properties, in healthy adolescents are scarce. Purpose To provide CMR derived reference values for biventricular mass, volumes and function measured by cine steady-state free-precession (SSFP) sequences and myocardial tissue relaxation properties as measured by native T1- and T2-mapping sequences in healthy adolescents. Methods A comprehensive non-contrast CMR study was performed in healthy adolescents aged 15 to 18 years enrolled in the “Early ImaginG Markers of unhealthy lifestyles in Adolescents” (EnIGMA) project using a 3-Tesla CMR scanner between March 2021 and October 2021. The imaging protocol included a cine SSFP to provide high-quality images for chamber size and function analysis, and a T2-GraSE mapping and native T1-mapping sequences (MOLLI Scheme 5 (3) 3) to provide precise myocardial relaxation time properties. Images were analyzed by experienced observers using the Cardiac Analysis tool available at IntelliSpace Portal following a standard protocol. In cine SSFP sequences, right and left ventricles were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation, respectively (Figure 1A, B). Native T1 and T2 maps were analyzed in a mid-ventricular short axis slice and summarized values per individual were determined (Figure 1C, D). Student's t-tests were used for between-gender comparisons. Results CMR scans were performed in 123 adolescents (63 girls, 51.2%) with a mean age of 16.0 years (standard deviation (SD)=0.5), mean body mass index of 21.4 (SD=3.2) kg/m2, mean body surface area of 1.69 (SD=0.16) m2, and mean heart rate during CMR acquisitions of 69 (SD=11) beats/minute. Reference percentiles (P) 3, 10, 25, 50, 75, 90 and 97 for the different parameters analyzed by gender are provided in Figure 2. Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.5 vs 78.1 ml/m2, p&amp;lt;0.01; and 101.1 vs 84.2 ml/m2, p&amp;lt;0.01), as well as the indexed cardiac mass (48.4 vs 36.4 g/m2, p&amp;lt;0.01). Left ventricular ejection fraction (LVEF) was similar in boys and girls (62.0 vs. 62.9%, p=0.23), whereas right ventricular ejection fraction was slightly lower in boys than in girls (55.3 vs. 57.1%, p=0.03). Mean myocardial native T1 relaxation time was 1253 (SD=28) ms in girls and 1215 (SD=23) ms in boys (p&amp;lt;0.01), whereas mean myocardial T2 relaxation time was 44.1 (SD=2.3) ms and 44.4 (SD=2.0) ms in girls and boys, respectively (p=0.46). Conclusion This study provided CMR derived reference values for biventricular anatomy, function, and myocardial tissue properties, in healthy adolescents aged 15 to 18 years. This information may be useful for the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in adolescent population. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III (ISCIII)-Fondo de Investigaciόn SanitariaEuropean Regional Development Fund/European Social Fund (“A way to make Europe”/“Investing in your future”)

Health-related quality of life scores of metastatic pancreatic cancer patients responsive to first line chemotherapy compared to newly derived EORTC QLQ-C30 reference values

BackgroundMetastatic pancreatic cancer (mPC) and its treatments significantly impact health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in germline BRCA mutated mPC patients who had not progressed during ≥16 weeks of first-line platinum-based chemotherapy. HRQoL was assessed using the EORTC QLQ-C30. To enhance score interpretation, we derived reference values for treatment-naïve mPC patients from the literature.MethodsA targeted literature review identified EORTC QLQ-C30 baseline values in treatment-naïve mPC patients. Reference values were calculated by deriving means from studies meeting inclusion criteria, with scores from 0 to 100 (higher scores indicate better QoL/functioning but worse symptoms). For POLO patients, means were calculated using pooled baseline data across study arms.ResultsFour studies met inclusion criteria. Depending on the specific scale, sample sizes ranged from n = 466 to n = 639. Compared to newly derived reference values, POLO patients reported markedly better HRQoL scores at baseline across most scales, with eight scales showing differences of ≥10 points. POLO patients’ HRQoL scores were often close to or better than general population norm data.ConclusionsThis is the first study to systematically derive EORTC QLQ-C30 reference values for mPC. POLO patients had better HRQoL scores than those in the literature and similar to general population data. Comparatively high HRQoL of POLO patients are likely due to effects of prior first-line treatment and resolution of chemotherapy-related symptoms, response shift, or a combination. Newly derived reference values can enhance interpretation of mPC patients’ HRQoL.Trial registrationThe POLO trial was registered on 9 July 2014 with ClinicalTrials.gov as NCT 02184195.

Global and Regional Gastric Emptying Parameters: Establishment of Reference Values and Comparison of Different Camera View Methods.

Purpose of the Study:The purpose of the study is to establish the reference values of global and regional gastric emptying parameters (GEPs) using a standard vegetarian meal acceptable to the Indian population and compare the values derived on different camera view methods.Materials and Methods:Thirty-six consecutive healthy subjects with age ≥18 years underwent gastric emptying scintigraphy using anterior, posterior, and left anterior oblique (LAO) views. GEP was derived based on decay corrected counts in regions of interest defined on the whole and proximal stomach. Counts in the anterior and posterior view images were used to derive GEP based on geometric mean (GM) method. Comparison of GEP among different camera view methods was done with Friedman test and post hoc Wilcoxon signed-rank test after Bonferroni correction. Reference values were derived based on percentiles.Results:Rapid gastric emptying based on GM method was defined as percent retention <20% at 1 h while delayed emptying as percent retention >40% and >5% at 2 h and 4 h, respectively. The reference range of half-time of gastric emptying was 23–109 min. The reference value of intragastric meal distribution at time t = 0 was >64%, while the reference range of retention index was 0.7–1.3. Although the overall distribution of GEP derived on different camera view methods could be statistically significant (P < 1.00), the small differences in the derived reference values are likely to be of no clinical significance.Conclusion:The reference values of GEPs established in this study can be generalized for the Indian population and may be applied to aid in clinical decision making. We recommend the GM method as the preferred method, although single view method (LAO preferred over anterior) can also be an acceptable alternative.

GHG emission requirements and benchmark values for Norwegian buildings

As a response to the Paris agreement, Norway is committed to reducing greenhouse gas (GHG) emissions by 50 percent by 2030. Highly energy-efficient buildings have a greater proportion of embodied GHG emissions from material use (55-87%) compared to operational emissions. A new national standard, NS3720:2018 a methodology for greenhouse gas emission calculations for buildings, has harmonised the life cycle assessment (LCA) calculation of environmental impacts arising from Norwegian buildings and has led to an increase in LCAs. This paper aims to collect life cycle GHG emission data on Norwegian building case studies to help form recommendations for national GHG emission requirements and benchmark values that can be used by the Research centre for zero emission neighbourhoods in smart cities (FME ZEN), Futurebuilt and in Norwegian building codes (TEK). To do this, a statistical analysis of a reference sample is carried out to provide bottom-up derived reference values. Empirical life cycle GHG emission data results are collected from Norwegian building case studies in the reference, design and as-built project phases, sampled from Norwegian programmes and research centres such as Futurebuilt, Framtidens Byer, ZEB and ZEN. Altogether 133 Norwegian building cases have been gathered from 2009-2020, covering 1,023,738m2 of heated floor area for 49,360 building users. A functional unit of ‘1m2 of heated floor area over a building lifetime of 60 years is used. The results show an interquartile range of 240-492 kgCO2eq/m2 or 4-8.2 kgCO2eq/m2/yr, a median of 396 kgCO2eq/m2 or 6.6 kgCO2eq/m2/yr and a mean of 324 kgCO2eq/m2 or 5,4 kgCO2eq/m2/yr for all building typologies in the as-built phase. These results can be used to form initial indications for GHG emission requirements and benchmark values in Norway.

Hypomagnesemia is underestimated in children with HNF1B mutations.

Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg. Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal. In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg2+. In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7mmol/l versus 79.7% when applying respective references. Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.

Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP) in Italian children and adolescents: Data from LIFE PERSUADED project

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4–14 years old) according to geographical macro-areas and areas, age and sex.Children from the South and the Centre of Italy showed higher median levels of DEHP, as a sum of its metabolites (48.14 and 47.80 μg/L), than those from the North (39.47 μg/L; p = 0.0090 and 0.0004, respectively). Considering the total population, boys are more exposed than girls (only as urinary volume), and children aged 4–6 years have higher median levels than those 7–10 and 11–14 years old. The derived reference values (RV95) for DEHP in children is 168 μg/L. The relative metabolic rates of DEHP, the background levels and, thus, the RV95, vary with the geographical area, age and sex, indicating that all these parameters should be considered in the risk assessment.

Reference values for the six-minute walk test in Nigerian adolescents aged 10 to 18 years

Objective: To determine baseline six-minute walk distance in Nigerian adolescents and establish its relationship with age, gender and anthropometric parameters. Methods: One hundred and eighty healthy adolescents (10 – 18 years) were recruited from three schools. Six-minute walk test was conducted as described by the American Thoracic Society. Demographic and anthropometric characteristics were related to achieve six-minute walk distance. A mathematical formula for predicting six-minute walk distance was generated. Results: The mean ± SD six-minute walk distance was 590.1 ± 72.02 m and was significantly longer in males (p= 0.001) among adolescents aged 10- 16 years. Age was the only characteristic significantly associated with six-minute walk distance following multiple linear regression analyses. The formulae, [six-minute walk distance = 317.3 + 21.5 x age (years) in males and 117 + 33.0 x age (years) in females] closely approximated to measured six-minute walk distance. Conclusion: This study has derived reference values for 6-minute walk test in adolescents; the use of these reference values should consider age and gender variations. Keywords: Exercise test; Six-minute-walk; Adolescents; Nigeria

Speckle tracking derived reference values of myocardial deformation and impact of cardiovascular risk factors - Results from the population-based STAAB cohort study.

AimsWe aimed to provide reference values for speckle-tracking derived systolic and diastolic myocardial deformation markers, and to determine their relation with age, sex, and cardiovascular risk factors.Methods and resultsThe Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study recruited a representative sample of the population of Würzburg, Germany, aged 30–79 years. In a sample of 1818 participants (52% female, mean age 54±12 years) global longitudinal peak systolic strain (GL-PSS, n = 1218), systolic (GL-SSR, n = 1506), and early (GL-EDSR, n = 1506) and late diastolic strain rates (GL-LDSR, n = 1500) were derived from 2D speckle tracking analysis. From a subgroup of 323 individuals without any cardiovascular risk factor, sex- and age-specific reference values were computed. GL-PSS, GL-SSR, and GL-EDSR were associated with sex, GL-EDSR decreased and GL-LDSR increased with age. In the total sample, dyslipidemia was associated with altered GL-PSS, GL-SSR, and GL-EDSR in women but not in men, whereas obesity was associated with less favorable GL-PSS and GL-EDSR in either sex. Hypertension impacted more adversely on systolic and diastolic myocardial deformation in women compared to men (all p<0.01).ConclusionThe female myocardium appeared more vulnerable to high blood pressure and dyslipidemia when compared to men, while obesity was associated with adverse myocardial deformation in either sex. The reference values for echocardiographic myocardial deformation provided for a non-diseased population and their here reported associations with cardiovascular risk factors will inform future observational and intervention studies regarding i) effect sizes and power calculation, ii) cross-study comparisons, and iii) categorization of myocardial deformation in specific patient groups.

Ab initio calculations of the concentration dependent band gap reduction in dilute nitrides

While being of persistent interest for the integration of lattice-matched laser devices with silicon circuits, the electronic structure of dilute nitride III/V-semiconductors has presented a challenge to ab initio computational approaches. The origin of the computational problems is the strong distortion exerted by the N atoms on most host materials. Here, these issues are resolved by combining density functional theory calculations based on the meta-GGA functional presented by Tran and Blaha (TB09) with a supercell approach for the dilute nitride Ga(NAs). Exploring the requirements posed to supercells, it is shown that the distortion field of a single N atom must be allowed to decrease so far that it does not overlap with its periodic images. This also prevents spurious electronic interactions between translational symmetric atoms, allowing us to compute band gaps in very good agreement with experimentally derived reference values. In addition to existing approaches, these results offer a promising ab initio avenue to the electronic structure of dilute nitride semiconductor compounds.

Clinical chemistry reference intervals of healthy adult populations in Gojjam Zones of Amhara National Regional State, Northwest Ethiopia.

BackgroundReference interval is crucial for disease screening, diagnosis, monitoring, progression and treatment efficacy. Due to lack of locally derived reference values for the parameters, clinicians use reference intervals derived from western population. But, studies conducted in different African countries have indicated differences between locally and western derived reference values. Different studies also indicated considerable variation in clinical chemistry reference intervals by several variables such as age, sex, geographical location, environment, lifestyle and genetic variation.ObjectiveThis study aimed to determine the reference intervals of common clinical chemistry parameters of the community of Gojjam Zones, Northwest Ethiopia.MethodPopulation based cross-sectional study was conducted from November 2015 to December 2016 in healthy adult populations of Gojjam zone. Data such as, medical history, physical examination and socio-demographic data were collected. In addition, laboratory investigations were undertaken to screen the population. Clinical chemistry parameters were measured using Mindray BS 200 clinical chemistry autoanalyzer as per the manufacturer’s instructions. Descriptive statistics was used to calculate mean, median and 95th percentiles. Independent sample T-test and one way ANOVA were used to see association between variables.ResultsAfter careful screening of a total of 799 apparently healthy adults who were consented for this study, complete data from 446 (224 females and 222 males) were included for the analysis. The mean age of both the study participants was 28.8 years. Males had high (P<0.05) mean and 2.5th-97.5th percentile ranges of ALT, AST, ALP, creatinine and direct bilirubin. The reference intervals of amylase, LDH, total protein and total bilirubin were not significantly different between the two sex groups (P>0.05). Mean, median, 95% percentile values of AST, ALP, amylase, LDH, creatinine, total protein, total bilirubin, and direct bilirubin across all age groups of participants were similar (P>0.05). But, there was a significant difference in the value of ALT (P<0.05). The reference intervals of ALT, total protein and creatinine were significantly (P<0.05) high in people having monthly income >1500 ETB compared to those with low monthly income. Significant (P<0.05) higher values of the ALT, ALP and total protein were observed in people living in high land compared to low land residences.ConclusionThe study showed that some of the common clinical chemistry parameters reference intervals of healthy adults in Gojjam zones were higher than the reference intervals generated from developed countries. Therefore, strict adherence to the reference values generated in developed countries could lead to inappropriate diagnosis and treatment of patients. There was also variation of reference interval values based on climate, gender, age, monthly income and geographical locations. Therefore, further study is required to establish reference intervals for Ethiopian population.

Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study.

Reference intervals for clinical laboratory parameters are important for assessing eligibility, toxicity grading and management of adverse events in clinical trials. Nonetheless, haematological and biochemical parameters used for clinical trials in sub-Saharan Africa are typically derived from industrialized countries, or from WHO references that are not region-specific. We set out to establish community reference values for haematological and biochemical parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We conducted a cross sectional study nested within phase II and III trials of RTS, S malaria vaccine candidate. We analysed 10 haematological and 2 biochemical parameters from 1,070 and 423 community children without illness prior to experimental vaccine administration. Statistical analysis followed Clinical and Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and their respective 90% confidence intervals were determined using non-parametric methods. Findings were compared with published ranges from Tanzania, Europe and The United States. We determined the reference ranges within the following age partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months to 17 months for the haematological parameters; and 4 weeks to 17 months for the biochemical parameters. There were no gender differences for all haematological and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference ranges in infants largely overlapped with those from United States or Europe, except for the lower limit for Hb, Hct and platelets (lower); and upper limit for platelets (higher) and haematocrit(lower). Community norms for common haematological and biochemical parameters differ from developed countries. This reaffirms the need in clinical trials for locally derived reference values to detect deviation from what is usual in typical children in low and middle income countries.

A modified Chevrel technique for ventral hernia repair: long-term results of a single centre cohort

PurposeTo evaluate the short- and long-term results after a modified Chevrel technique for midline incisional hernia repair, regarding surgical technique, hospital stay, wound complications, recurrence rate, and postoperative quality of life. These results will be compared to the literature derived reference values regarding the original and modified Chevrel techniques.MethodsIn this large retrospective, single surgeon, single centre cohort all modified Chevrel hernia repairs between 2000 and 2012 were identified. Results were obtained by reviewing patients’ medical charts. Postoperative quality of life was measured using the Carolina Comfort Scale. A multi-database literature search was conducted to compare the results of our series to the literature based reference values.ResultsOne hundred and fifty-five patients (84 male, 71 female) were included. Eighty patients (52%) had a large incisional hernia (width ≥ 10 cm) according the definition of the European Hernia Society. Fourteen patients (9%) underwent a concomitant procedure. Median length-of-stay was 5 days. Within 30 days postoperative 36 patients (23.2%) had 39 postoperative complications of which 30 were mild (CDC I–II), and nine severe (CDC III–IV). Thirty-one surgical site occurrences were observed in thirty patients (19.4%) of which the majority were seroma (16 patients 10.3%). There was no hernia-related mortality during follow-up. Recurrence rate was 1.8% after a median follow-up of 52 months (12–128 months). Postoperative quality of life was rated excellent.ConclusionsThe modified Chevrel technique for midline ventral hernias results in a moderate complication rate, low recurrence rate and high rated postoperative quality of life.

Comprehensive radionuclide esophagogastrointestinal transit study: methodology, reference values, and initial clinical experience.

A radionuclide methodology and reference values have been developed for a single gastrointestinal transit study including esophageal transit, liquid and solid gastric emptying, and small- and large-bowel transit, using (111)In-diethylenetriaminepentaacetic acid (DTPA) with the standardized (99m)Tc-labeled solid meal. Eighteen healthy subjects and 18 patients were investigated. The esophageal transit study was performed with 3.7 MBq (0.1 mCi) of (111)In-DTPA in 15 mL of water. A liquid-only 30-min gastric-emptying study followed, with ingestion of 3.7 MBq (0.1 mCi) of (111)In-DTPA in 300 mL of water. Then, a simultaneous solid-liquid emptying study was acquired after ingestion of a solid (99m)Tc-sulfur colloid-labeled meal and 7.4 MBq (0.2 mCi) of (111)In-DTPA in 120 mL of water. Images were acquired intermittently for 4 h. Additional (111)In images were acquired at 5 and 6 h to measure small-bowel transit, and at 24, 48, and 72 h for large-bowel transit. Reference values were determined for esophageal transit (transit time, percentage emptying at 10 s), liquid-only gastric emptying (emptying half-time), liquid and solid emptying in a dual-phase solid-liquid study (emptying half-time and percentage emptying at 1, 2, 3, and 4 h), small-bowel transit index (percentage transit to ileocecal valve at 6 h), and colonic transit (geometric center and percentage colonic emptying) at 24, 48, and 72 h. Results from the first 18 patients found abnormal transit in 72% (13/18); clinical management changed in 61% (11/18). We have developed a radionuclide methodology and derived reference values for a comprehensive gastrointestinal transit study using (111)In-DTPA with the standardized (99m)Tc-labeled solid meal. Our initial clinical experience suggests clinical value.

Biochemical and Hematologic Parameters for Children in the Middle Belt of Ghana

Reference values derived from developed countries are used in many countries in Africa for interpretation of laboratory results obtained during routine healthcare and clinical trials. Use of locally derived reference values has been recommended. The purpose of the study was to establish age- and sex-specific reference values for children in the middle belt of Ghana. Reference values were determined for 21 biochemical and 18 hematologic parameters by using Clinical and Laboratory Standards Institute C28-A3 guidelines in a sample of 1,442 healthy children. Hemoglobin, hematocrit, mean cell volume, erythrocytes, urea, and creatinine were lower when compared with values from northern countries but alanine aminotransferase, aspartate aminotransferase, and total bilirubin were higher. A panel of locally relevant age- and sex-specific reference values was established for commonly used biochemical and hematologic tests in children in the middle part of Ghana. This will help in interpretation of laboratory results for clinical management of patients, screening, and safety monitoring during clinical trials.