Human Milk Oligosaccharides and Bacterial Profile Modulate Infant Body Composition during Exclusive Breastfeeding.

Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.

Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.

Overcoming inefficiencies arising due to the impact of the modifiable areal unit problem on single-aggregation disease maps.

BACKGROUND: In disease mapping, fine-resolution spatial health data are routinely aggregated for various reasons, for example to protect privacy. Usually, such aggregation occurs only once, resulting in 'single-aggregation disease maps' whose representation of the underlying data depends on the chosen set of aggregation units. This dependence is described by the modifiable areal unit problem (MAUP). Despite an extensive literature, in practice, the MAUP is rarely acknowledged, including in disease mapping. Further, despite single-aggregation disease maps being widely relied upon to guide distribution of healthcare resources, potential inefficiencies arising due to the impact of the MAUP on such maps have not previously been investigated. RESULTS: We introduce the overlay aggregation method (OAM) for disease mapping. This method avoids dependence on any single set of aggregate-level mapping units through incorporating information from many different sets. We characterise OAM as a novel smoothing technique and show how its use results in potentially dramatic improvements in resource allocation efficiency over single-aggregation maps. We demonstrate these findings in a simulation context and through applying OAM to a real-world dataset: ischaemic stroke hospital admissions in Perth, Western Australia, in 2016. CONCLUSIONS: The ongoing, widespread lack of acknowledgement of the MAUP in disease mapping suggests that unawareness of its impact is extensive or that impact is underestimated. Routine implementation of OAM can help avoid resource allocation inefficiencies associated with this phenomenon. Our findings have immediate worldwide implications wherever single-aggregation disease maps are used to guide health policy planning and service delivery.

Improving the Efficiency of Geographic Target Regions for Healthcare Interventions.

Appropriate prioritisation of geographic target regions (TRs) for healthcare interventions is critical to ensure the efficient distribution of finite healthcare resources. In delineating TRs, both 'targeting efficiency', i.e., the return on intervention investment, and logistical factors, e.g., the number of TRs, are important. However, existing approaches to delineate TRs disproportionately prioritise targeting efficiency. To address this, we explored the utility of a method found within conservation planning: the software Marxan and an extension, MinPatch ('Marxan + MinPatch'), with comparison to a new method we introduce: the Spatial Targeting Algorithm (STA). Using both simulated and real-world data, we demonstrate superior performance of the STA over Marxan + MinPatch, both with respect to targeting efficiency and with respect to adequate consideration of logistical factors. For example, by design, and unlike Marxan + MinPatch, the STA allows for user-specification of a desired number of TRs. More broadly, we find that, while Marxan + MinPatch does consider logistical factors, it also suffers from several limitations, including, but not limited to, the requirement to apply two separate software tools, which is burdensome. Given these results, we suggest that the STA could reasonably be applied to help prevent inefficiencies arising due to targeting of interventions using currently available approaches.

Impact of APOE-ε4 carriage on the onset and rates of neocortical Aß-amyloid deposition.

Neocortical Aß-amyloid deposition, one of the hallmark pathologic features of Alzheimer's disease (AD), begins decades prior to the presence of clinical symptoms. As clinical trials move to secondary and even primary prevention, understanding the rates of neocortical Aß-amyloid deposition and the age at which Aß-amyloid deposition becomes abnormal is crucial for optimizing the timing of these trials. As APOE-ε4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-ε4 carriage on the age at which the neocortical Aß-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over 3 years of follow-up, abnormal levels of neocortical Aß-amyloid were reached on average at age 72 (66.5-77.1). The APOE-ε4 carriers reached abnormal levels earlier at age 63 (59.6-70.3); however, noncarriers reached the threshold later at age 78 (76.1-84.4). No differences in the rates of deposition were observed between APOE-ε4 carriers and noncarriers after abnormal Aß-amyloid levels had been reached. These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-ε4 carriers between the ages of 60 and 66 and noncarriers between the ages of 76 and 84.

Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions.

BACKGROUND: Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology. METHODS: We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95 days (median, range 0-735 days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-α; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model. RESULTS: Significant decreases were observed over time in pleural fluid protein by 8 g/L per 100 days (SE, 1.32; P < .0001) and pH (0.04/100 days; SE, 0.02; P = .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100 days (SE, 0.02; P = .04). MPEs from mesothelioma (n = 63) had lower pleural fluid glucose (P = .0104) at baseline and a faster rate of decline in glucose (P = .0423) when compared with non-mesothelioma effusions (n = 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100 days; SE, 0.13; P = .0046), but not of other cytokines, was observed. CONCLUSIONS: MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE.

Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy.

We describe a study of the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy. Diffuse reflectance spectra in the wavelength range 550 to 1000 nm are obtained using 400-microm core multimode fibers arranged in a six-illumination-around-one-collection geometry with a single fiber-fiber spacing of 470 microm. Spectra are collected at specific locations on 120 pigmented lesions selected by clinicians as possible melanoma, including 64 histopathologically diagnosed as melanoma. These locations are carried through to the histopathological diagnosis, permitting a spatially localized comparison with the corresponding spectrum. The variations in spectra between groups of lesions with different diagnoses are examined and reduced to features suitable for discriminant analysis. A classifier distinguishing between benign and malignant lesions performs with sensitivity/specificity of between 6469% and 7278%. Classifiers between pairs of the group common nevus, dysplastic nevus, in situ melanoma, and invasive melanoma show better or similar performance than the benign/malignant classifier, and analysis provides evidence that different spectral features are needed for each pair of groups. This indicates that multiple discriminant systems are likely to be required to distinguish between melanoma and similar lesions.

A comparison of Demirjian's four dental development methods for forensic age estimation in South Australian sub-adults.

The aim of this study was to compare the accuracy of Demirjian's four dental development methods for forensic age assessment in a South Australian population. The sample comprised orthopantomograms (OPGs) of 408 sub-adult individuals (211 male; 197 female) with an age range of 4.9-14.5 years. The OPGs were obtained from various dental schools and clinics in urban Adelaide. The following Demirjian methods were evaluated: the original 7-tooth technique; the revised 7-tooth system; the 4-tooth method; and the alternate 4-tooth approach. The left mandibular teeth in each OPG were assessed and rated according to the eight stages (A-H) defined and illustrated in Demirjian et al.(5) Differences between chronological and estimated ages were calculated for males and females separately; 95% confidence intervals of mean age differences were calculated and ANOVA used to assess the significance of mean differences. When comparing all four methods there were significant differences overall (and in individual age groups) between mean chronological and estimated age in both sexes. In addition, each method consistently overestimated chronological age. We also demonstrate that the accuracy of the dental age methods evaluated varies in different subsets of an Australian population, a finding that parallels previous research in other global populations. Based on our analyses we conclude that population-specific standards based on dental maturity curves, as opposed to estimated ages, would provide more accurate and statistically robust age estimations.

A comparison of Demirjian's four dental development methods for forensic age assessment.

The aim of this study was to determine the comparative accuracy of Demirjian's four dental development methods for forensic age estimation in the Western Australian population. A sample comprising 143 individuals aged 4.6 to 14.5 years were assessed using Demirjian's four methods for dental development (original 7-tooth: M(2), M(1), PM(2), PM(1), C, I(2), and I(1); revised 7-tooth: M(2), M(1), PM(2), PM(1), C, I(2), and I(1); 4-tooth: M(2), M(1), PM(2), and PM(1); and an alternate 4-tooth: M(2), PM(2), PM(1), and I(1)). When comparing all four methods, the 4-tooth method overestimated age in both males and females by 0.04 and 0.25 years, respectively. The original 7-tooth was least accurate for males, while the original 7-tooth, the revised 7-tooth, and the alternate 4-tooth were unsuitable for females. Therefore, we recommend the 4-tooth method to be used for forensic age estimation in Western Australian males and females, as it has the lowest overall mean deviation and the highest accuracy.

To evaluate the utility of smaller sample sizes when assessing dental maturity curves for forensic age estimation.

Dental maturation and chronological age estimation were determined from 144 healthy Western Australian individuals aged 3.6-14.5 years. The results were compared with Farah et al.'s previous study which comprised a larger heterogeneous sample of Western Australian individuals (n = 1450). Orthopantomograms were analyzed with the application of Demirjian and Goldstein's 4-tooth method based on eight stages of dental mineralization. Analysis of variance revealed no significant differences in dental maturity scores in each age group among the males in both studies; similar results were seen in the females. Paired t-tests showed no statistical significance overall between chronological and estimated ages for the males in our sample (p = 0.181), whereas the females showed significant differences (p < 0.001). Our results show that smaller samples may be used when assessing dental maturity curves for forensic age estimation.