An approach to post‐radical trachelectomy vaginal‐isthmus cytology

Radical trachelectomy (RT) is the surgical amputation of the uterine cervix with paracervical lymphadenectomy, performed in reproductive age women to treat invasive squamous‐cell carcinoma or endocervical adenocarcinoma while preserving the uterine corpus for potential child bearing. Post‐RT patient monitoring includes isthmic‐vaginal cytology. This study reviews our experience with liquid based preparation of post‐RT cytology samples. Fifty‐four post‐RT vaginal‐isthmic cytology specimens were reviewed from nine patients, seven with adenocarcinoma, and two with squamous‐cell carcinoma. Five patients had normal (NILM) or normal with reactive changes on all cytology samples. Two patients had isolated squamous abnormalities (atypical squamous‐cells of uncertain significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL)); both follow‐up biopsies were negative. Two patients had repeatedly abnormal specimens interpreted as atypical glandular cells (AGC), one of whom also had a concurrent ASC‐US. Only one sample was tested for high risk human papilloma virus (hrHPV), with negative results. All patients with abnormal cytology went on to have biopsies which were interpreted as benign. The cytology specimens most often interpreted as AGC contained many groups of hyperchromatic crowded glandular cells and/or stromal cells derived from direct sampling of the lower uterine segment. The crowding often limits visualization of all the cells in a group, plus sampled endometrium may harbor mitoses, adding to the atypical appearance. Cytologists should become familiar with the spectrum of changes in the post‐RT cytology. Testing for hrHPV should be considered for use in the management of abnormal cytology results. Post RT cytology should be compared with presurgical cytology since one would anticipate similarities in post‐RT true positive cases. In particular, a primary diagnosis of adenocarcinoma makes differentiating benign reactive glandular cells from recurrence a critical issue. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Nineteenth‐century population structure of Ireland and of the Irish in England and Wales: An analysis by isonymy

This article uses isonymy to test predictions about the genetic structure of Irish populations made on the basis of geography and population history, and compares the mid‐nineteenth century population of Ireland with the late nineteenth century Irish‐born population resident in England and Wales. Surname data were derived from (1) the householders named in the index to Griffith's valuation of Ireland, a survey undertaken between 1846 and 1864, and (2) of Irish‐born residents named in 1881 census of England and Wales. Visual representation of the Griffith's valuation isonymy matrix by multidimensional scaling (MDS) gives a result very close to the geographical distribution of Irish counties, and Mantel matrix correlation shows random isonymy between counties to be negatively associated with geographical distance, generally decaying according to a pattern of isolation‐by‐distance, with exceptions that can be explained in terms of Irish population history. Some 141,360 Irish‐born residents in England and Wales at the 1881 census were assigned to an Irish county of origin, and random isonymy by county of birth for this group also shows a close correspondence to Irish geography. The Mantel matrix correlation between the Irish in Ireland and the Irish in England is 0.855, R² = 0.7306, indicating that the emigrant Irish in England were representative of the populations of the Irish counties from which they were derived. This result, together with the strong geographical patterning of surnames in Ireland, suggests that isonymy can be used to investigate the population structure and origin of Irish emigrant groups in Britain and potentially throughout the Irish diaspora. Am. J. Hum. Biol. 2009. © 2008 Wiley‐Liss, Inc.     

Sex differences in the consequences of early‐life exposure to epidemiological stress—A life‐history approach

Objectives: Exposure to infectious disease in early life has been suggested to have a negative effect on later‐life survival, possibly through the induction of inflammatory responses. Although a life‐course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early‐life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. Methods: To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a nonexposed group. The exposed group comprised those exposed to a high‐infectious disease load during prenatal and early postnatal development. Results: The results show a marked sex difference in the impact of early‐life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. Conclusions: This study does not support former studies indicating a negative association between early‐life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.     

Hierarchical non‐negative matrix factorization to characterize brain tumor heterogeneity using multi‐parametric MRI

Tissue characterization in brain tumors and, in particular, in high‐grade gliomas is challenging as a result of the co‐existence of several intra‐tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow‐up of individual patients. Twenty‐four patients with glioma [10 low‐grade gliomas (LGGs), 14 high‐grade gliomas (HGGs)] underwent a multi‐parametric MRI (MP‐MRI) scheme, including conventional MRI (cMRI), perfusion‐weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short‐TE ¹H MRSI. MP‐MRI parameters were derived: T₂, T₁ + contrast, fluid‐attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N‐acetyl‐aspartate (NAA), total choline (Cho), etc. Hierarchical non‐negative matrix factorization (hNMF) was applied to the MP‐MRI parameters, providing tissue characterization on a patient‐by‐patient and voxel‐by‐voxel basis. Tissue‐specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities. Copyright © 2015 John Wiley & Sons, Ltd.     

Adolescents' sense of community on myspace and facebook: a mixed‐methods approach

Communities are foundational to the field of Community Psychology yet they are difficult to define and measure. Once viewed as social groups with ties to geographical locations, online communities interact free of physical or face‐to‐face contact. This cyberexistence makes the study of communities more challenging. Social networking sites (SNS), such as Facebook and MySpace, are referred to as online communities; however, research has yet to explore whether these sites engender a psychological sense of community (PSC) for users. This study reanalyzes focus group and survey data from high school and college students to investigate whether uses of SNS demonstrate key components of PSC (i.e., membership, influence, immersion, shared emotional connection, and an integration and fulfillment of needs). This mixed‐method analysis synthesizes data through a top‐down (confirming PSC categories) and bottom‐up (identifying emergent patterns/themes) analytic procedure. Results suggest that typical adolescent uses of SNS represent networked individualism, rather than online communities. © 2010 Wiley Periodicals, Inc.     

Independent changes in female body shape with parity and age: A life‐history approach to female adiposity

Both aging and reproduction have been shown to influence female body shape in industrialized populations, involving redistribution of fat from lower to upper body regions. However, the extent to which effects of parity vary by age and the extent to which age affects shape independent of parity remain unclear. We studied shape variability in relation to age and parity in a cross‐sectional survey of 4,130 white British women, using three‐dimensional photonic scanning. In women ≤40 years, bearing children was associated with increased abdominal and reduced thigh girths, independent of age and BMI. Very few such differences were statistically significant in women >40 years, suggesting the effects of parity on shape wash out over time. In nulliparous women, aging was associated with shape variability, independent of BMI, with a similar pattern of associations evident in women both ≤40 and >40 years. Our data support previous findings of “covert maternal depletion” in relation to parity, but show that this is merely a more pronounced component of a general strategic shift of fat from lower to upper body with age. These findings are consistent with a life‐history model of female energy stores being allocated to competing “reproduction” and “maintenance” depots, with the optimal trade‐off strategy changing with age and with that strategic shift accelerated by bearing children. This model is relevant to the “grandmother hypothesis.” The dual effects of age and parity on fat distribution substantially resolve by old age the profound sexual dimorphism in adiposity present at the start of adult life. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.     

Optimized truncation to integrate multi‐channel MRS data using rank‐R singular value decomposition

Multi‐channel phased receive arrays have been widely adopted for magnetic resonance imaging (MRI) and spectroscopy (MRS). An important step in the use of receive arrays for MRS is the combination of spectra collected from individual coil channels. The goal of this work was to implement an improved strategy termed OpTIMUS (i.e., op timized t runcation to i ntegrate m ulti‐channel MRS data u sing rank‐R s ingular value decomposition) for combining data from individual channels. OpTIMUS relies on spectral windowing coupled with a rank‐R decomposition to calculate the optimal coil channel weights. MRS data acquired from a brain spectroscopy phantom and 11 healthy volunteers were first processed using a whitening transformation to remove correlated noise. Whitened spectra were then iteratively windowed or truncated, followed by a rank‐R singular value decomposition (SVD) to empirically determine the coil channel weights. Spectra combined using the vendor‐supplied method, signal/noise² weighting, previously reported whitened SVD (rank‐1), and OpTIMUS were evaluated using the signal‐to‐noise ratio (SNR). Significant increases in SNR ranging from 6% to 33% (P ≤ 0.05) were observed for brain MRS data combined with OpTIMUS compared with the three other combination algorithms. The assumption that a rank‐1 SVD maximizes SNR was tested empirically, and a higher rank‐R decomposition, combined with spectral windowing prior to SVD, resulted in increased SNR.     

Clinical Immunology Review Series: An approach to the patient with angio‐oedema

Angio‐oedema is a common reason for attendance at the accident and emergency department and for referral to immunology/allergy clinics. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. Failure to identify the more unusual causes of angio‐oedema may result in life‐threatening situations. Common and rare causes of angio‐oedema will be discussed in this article, as well as the diagnostic and treatment pathways for the management of these patients. A comprehensive history and close monitoring of response to treatment are the most cost‐effective diagnostic and treatment tools.     

An approach to understanding sleep and depressed mood in adolescents: person‐centred sleep classification

Depressive mood in youth has been associated with distinct sleep dimensions, such as timing, duration and quality. To identify discrete sleep phenotypes, we applied person‐centred analysis (latent class mixture models) based on self‐reported sleep patterns and quality, and examined associations between phenotypes and mood in high‐school seniors. Students (n = 1451; mean age = 18.4 ± 0.3 years; 648 M) completed a survey near the end of high‐school. Indicators used for classification included school night bed‐ and rise‐times, differences between non‐school night and school night bed‐ and rise‐times, sleep‐onset latency, number of awakenings, naps, and sleep quality and disturbance. Mood was measured using the total score on the Center for Epidemiologic Studies‐Depression Scale. One‐way anova tested differences between phenotype for mood. Fit indexes were split between 3‐, 4‐ and 5‐phenotype solutions. For all solutions, between phenotype differences were shown for all indicators: bedtime showed the largest difference; thus, classes were labelled from earliest to latest bedtime as ‘A’ (n = 751), ‘B’ (n = 428) and ‘C’ (n = 272) in the 3‐class solution. Class B showed the lowest sleep disturbances and remained stable, whereas classes C and A each split in the 4‐ and 5‐class solutions, respectively. Associations with mood were consistent, albeit small, with class B showing the lowest scores. Person‐centred analysis identified sleep phenotypes that differed in mood, such that those with the fewest depressive symptoms had moderate sleep timing, shorter sleep‐onset latencies and fewer arousals. Sleep characteristics in these groups may add to our understanding of how sleep and depressed mood associate in teens.     

The association between family history of mental disorder and delusional‐like experiences: A general population study

Recent studies have indicated that isolated delusional‐like experiences (DLE) are common in the general population. Furthermore, there is preliminary evidence to suggest that these experiences are more common in those with a family history of mental disorders. We had the opportunity to explore the association between family history of a wide range of mental disorders and DLE in an Australian general population survey. The Australian National Survey of Mental Health and Wellbeing 2007 examined 8,841 adult community residents. The Composite International Diagnostic Interview was used to generate various DSM‐IV lifetime diagnoses and to assess DLE. The participants were asked to report mental disorders in their first‐degree relatives. The influence of family history of mental disorders on DLE endorsement was assessed with logistic regression, with adjustments for age, sex, and the presence of comorbid psychiatric diagnoses in the respondents. A family history of anxiety, depression, schizophrenia, bipolar disorder, or alcohol or illicit drug abuse/dependence was each significantly associated with endorsement of DLE, and these associations remained significant when we adjusted for the presence of mental illness in the respondents. When we examined a more restrictive definition of DLE, only a family history of depression and schizophrenia remained significantly associated with DLE. DLE are associated with a family history of a wide range of mental disorders. These findings suggest that familial factors associated with DLE may be shared with a wide range of common mental disorders. © 2011 Wiley‐Liss, Inc.     

Genetic structure and population history of Ireland: a comparison of blood group and anthropometric analyses

Population structure and history may be studied on a local or a regional level. This paper examines the regional population structure of the Republic of Ireland and Northern Ireland with respect to population history and demographic processes. Blood-group and anthropometric data obtained from the literature are analysed. The blood-group data consist of ABO and Rhesus gene frequencies for 32 counties and the Aran Islands. Anthropometric data consist of summary statistics for 15 variables collected from 19 regions. The degree and pattern of population differentiation is assessed using new methods of population-structure analysis. Both blood group and anthropometric analyses show a west-east division of populations corresponding to the known history of inhabitation of Ireland, where successive waves of immigrants pushed earlier populations further west. In both analyses there were two deviations to this basic pattern: the Aran Islands and the midlands. In both cases, alternative historical explanations are examined. The genetic relationship of the Aran Islands to the rest of Ireland and England appears to be due to English admixture following the garrisoning of soldiers several centuries ago. The genetic position of the midlands is more complex, but suggests the effects of early Viking inhabitation. These findings are related to studies of the local, rather than regional, population structure of Ireland.     

An approach to diagnosis and treatment in the migrant allergic population.

An approach to allergy diagnosis and treatment in the migrant population of the United States is derived from a review of selected aspects of pollen aerobiology and the nature and distribution of allergenic plants. Pollen distribution and importance are defined and divided into four relatively homogenous geographic regions of the continental United States. Botanic relationships between pollens are then summarized, especially as they relate to the methodology and results of studies of antigenic relationships between pollens. From this information, 13 mixes of tree pollens, 12 mixes of grass pollens, and 12 mixes of week pollens are proposed which would include the pollens of major and secondary importance found in the four defined geographic regions and which would be appropriate for puncture testing. Further grouping of antigens is described for use in intradermal testing and formulating treatment mixtures. A sample skin test sheet is presented which summarizes this information in a practical format.     

A geometric morphometric approach to the quantification of population variation in sub‐Saharan African crania

We report here on new data examining cranial variation in 18 modern human sub‐Saharan African populations. Previously, we investigated variation within southern Africa; we now extend our analyses to include a series of Central, East, and West African crania, to further knowledge of the relationships between, and variation and regional morphological patterning in, those populations. The sample comprises 377 male individuals; the three‐dimensional coordinates of 96 landmarks are analyzed using Procrustes‐based methods. Interpopulation variation is examined by calculating shape distances between groups, which are compared using resampling statistics and parametric tests. Phenotypic variance, as a proxy for genetic variance, is measured and compared across populations. Principal components and cluster analyses are employed to explore relationships between the populations. Shape differences are visualized using three‐dimensional rendered models. Observed disparity patterns imply a mix of differences and similarities across populations, with no apparent support for genetic bottlenecks, which is likely a consequence of migrations that may have influenced differences in cranial form; supporting data are found in recent molecular studies. The Pygmy sample had the most distinctive cranial morphology; characteristically small in size with marked prognathism. These features characterized, although less strongly, the neighboring Bateke, and are possibly related to similar selective pressures in conjunction with interbreeding. Small cranial size is also involved in the considerable distinctiveness of the San and Khoikhoi. The statistical procedures applied in this study afford a powerful and robust means of quantifying and visualizing the magnitude and pattern of cranial variation between sub‐Saharan African populations. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

An eigenvalue approach for the automatic scaling of unknowns in model‐based reconstructions: Application to real‐time phase‐contrast flow MRI

The purpose of this work is to develop an automatic method for the scaling of unknowns in model‐based nonlinear inverse reconstructions and to evaluate its application to real‐time phase‐contrast (RT‐PC) flow magnetic resonance imaging (MRI). Model‐based MRI reconstructions of parametric maps which describe a physical or physiological function require the solution of a nonlinear inverse problem, because the list of unknowns in the extended MRI signal equation comprises multiple functional parameters and all coil sensitivity profiles. Iterative solutions therefore rely on an appropriate scaling of unknowns to numerically balance partial derivatives and regularization terms. The scaling of unknowns emerges as a self‐adjoint and positive‐definite matrix which is expressible by its maximal eigenvalue and solved by power iterations. The proposed method is applied to RT‐PC flow MRI based on highly undersampled acquisitions. Experimental validations include numerical phantoms providing ground truth and a wide range of human studies in the ascending aorta, carotid arteries, deep veins during muscular exercise and cerebrospinal fluid during deep respiration. For RT‐PC flow MRI, model‐based reconstructions with automatic scaling not only offer velocity maps with high spatiotemporal acuity and much reduced phase noise, but also ensure fast convergence as well as accurate and precise velocities for all conditions tested, i.e. for different velocity ranges, vessel sizes and the simultaneous presence of signals with velocity aliasing. In summary, the proposed automatic scaling of unknowns in model‐based MRI reconstructions yields quantitatively reliable velocities for RT‐PC flow MRI in various experimental scenarios.     

An approach to AIDS therapy using hyperthermia and membrane modification

Altering the biophysical characteristics of cell membranes by diet and membrane perturbing agents markedly influences thermosensitivity of cells. Likewise, manipulation of viral envelopes either by altering their lipid composition by diet or by the use of agents that perturb the lipid envelope influence infectivity of enveloped viruses and the progression of viral disease. The use of hyperthermia and envelope modification as a combined approach to treat AIDS has until now neither been suggested nor attempted. On the basis of my previous work and a review of the literature, I theorize that the combination of hyperthermia with procedures designed to alter the viral envelope will likely result in an increased viral sensitivity and be useful clinically for treatment of patients with enveloped viral diseases such as AIDS.     

SARS‐CoV‐2: An immunogenetics call to arms

Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS‐Cov‐2 pandemic, this review considers existing immunogenetic knowledge of virus‐immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.