The relation between child death and child maltreatment.

The death of a child is a sentinel event in a community, and a defining marker of a society's policies of safety and health. Child death as a result of abuse and neglect is a tragic outcome that occurs in all nations of the world. The true incidence of fatal child abuse and neglect is unknown. The most accurate incidence data of such deaths have been obtained from countries where multi-agency death review teams analyse the causes of child fatalities, as is done in the United States and Australia.     

Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.

PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.     

Robust-Deep: A Method for Increasing Brain Imaging Datasets to Improve Deep Learning Models’ Performance and Robustness

A small dataset commonly affects generalization, robustness, and overall performance of deep neural networks (DNNs) in medical imaging research. Since gathering large clinical databases is always difficult, we proposed an analytical method for producing a large realistic/diverse dataset. Clinical brain PET/CT/MR images including full-dose (FD), low-dose (LD) corresponding to only 5 % of events acquired in the FD scan, non-attenuated correction (NAC) and CT-based measured attenuation correction (MAC) PET images, CT images and T1 and T2 MR sequences of 35 patients were included. All images were registered to the Montreal Neurological Institute (MNI) template. Laplacian blending was used to make a natural presentation using information in the frequency domain of images from two separate patients, as well as the blending mask. This classical technique from the computer vision and image processing communities is still widely used and unlike modern DNNs, does not require the availability of training data. A modified ResNet DNN was implemented to evaluate four image-to-image translation tasks, including LD to FD, LD+MR to FD, NAC to MAC, and MRI to CT, with and without using the synthesized images. Quantitative analysis using established metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), and joint histogram analysis was performed for quantitative evaluation. The quantitative comparison between the registered small dataset containing 35 patients and the large dataset containing 350 synthesized plus 35 real dataset demonstrated improvement of the RMSE and SSIM by 29% and 8% for LD to FD, 40% and 7% for LD+MRI to FD, 16% and 8% for NAC to MAC, and 24% and 11% for MRI to CT mapping task, respectively. The qualitative/quantitative analysis demonstrated that the proposed model improved the performance of all four DNN models through producing images of higher quality and lower quantitative bias and variance compared to reference images.     

Lipopolysaccharide mouse models for Parkinson’s disease research: a critical appraisal

Parkinson’s disease, the most common movement disorder, has a strong neuroinflammatory aspect. This is evident by increased pro-inflammatory cytokines in the serum, and the presence of activated microglial cells, and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson’s disease patients. The central and peripheral neuroinflammatory aspects of Parkinson’s disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide, a component of the cell wall of gram-negative bacteria. In this mini-review, we will critically evaluate different routes of lipopolysaccharide administration (including intranasal systemic and stereotasic), their relevance to clinical Parkinson’s disease as well as the recent findings in lipopolysaccharide mouse models. We will also share our own experiences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.Key Words: C57BL/6 mice, intranasal models, lipopolysaccharide models, neuroinflammation, Parkinson’s disease, stereotaxic models, substantia nigra, systemic models     

Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.     

Clinical presentation of fibroids

Uterine fibroids, the most common tumours in women of reproductive age, are asymptomatic in at least 50% of afflicted women. However, in other women, they cause significant morbidity and affect quality of life. Clinically, they present with a variety of symptoms: menstrual disturbances including menorrhagia, dysmenorrhoea and intermenstrual bleeding; pelvic pain unrelated to menstruation; and pressure symptoms such as a sensation of bloatedness, increased urinary frequency and bowel disturbance. In addition, they may compromise reproductive function, possibly contributing to subfertility, early pregnancy loss and later pregnancy complications such as pain, preterm labour, malpresentations, increased need for caesarean section, and postpartum haemorrhage. Large fibroids may distend the abdomen, which may be aesthetically displeasing to many women. Abnormal bleeding occurs in 30% of symptomatic women, and abnormal bleeding, bloating and pelvic discomfort due to mass effect constitute the most common symptoms. The incidence of fibroids is highest in Black women, who tend to have multiple and larger fibroids, and more symptomatic fibroids at the time of diagnosis. The prevalence of clinically significant myomas peaks in the perimenopausal years and declines after the menopause. It is not known why some fibroids are symptomatic while others are quiescent. The size, number and location of fibroids undoubtedly determine their clinical behaviour, but research has yet to correlate these parameters with clinical presentation of the fibroids.     

The risks for very low birth weight infants from multiple pregnancies

Advances in perinatal and neonatal care in recent years have resulted in dramatic improvements in the rate of intact survival of preterm infants. As a result, neonatologists have focused on the new challenge of bringing about similar advances for the tiniest infants who are born at or near the current limits of viability. Although these tiny infants comprise only a small proportion of all births, the ravages of prematurity make them by far the most challenging group of infants who require our attention in the neonatal intensive care unit.     

Comparison between singleton- and triplet-specific "growth" curves to detect growth restricted triplet infants

OBJECTIVE: To evaluate whether triplet- or singleton-specific growth standards should be used to define the growth restricted triplet fetus/neonate. STUDY DESIGN: We retrospectively compared the predictive values of singleton vs. triplet-specific "growth" standards using the neonatal ponderal index as reference for growth restriction. RESULTS: A ponderal index <1 SD from the mean was found in 356 (14.4%) of 2477 triplet infants. A total of 686 (27.7%) infants were small for gestational age (SGA) by singleton standards, but only 168 (6.8%) by triplet standards. After 31 weeks' gestation, triplet standards are significantly better associated with a low ponderal index (OR 2.0, 95% CI 1.1, 3.4 at 32 weeks to OR 4.1, 95% CI 2.8, 6.3 at 36-37 weeks), resulting in better positive predictive value and higher specificity of triplet standards in predicting a low ponderal index. CONCLUSION: Triplet birth weight standards are better than singleton standards at >31 but not at < or =31 weeks' gestation in predicting a low neonatal ponderal index.     

Controlled natural cycle IVF: experience in a world of stimulation

A total of 134 controlled natural IVF (nIVF) cycles were reviewed retrospectively and compared with 370 stimulated IVF (sIVF) cycles. The clinical pregnancy rate per embryo transfer following nIVF was 27% and 47% in sIVF cycles for patients aged less than 35. However, natural cycle patients could attempt consecutive cycles with much less impact on their lives, both medically and financially. In patients under 35 years of age, the choice of controlled nIVF reduces the cost and risk to the patient, permitting her to have multiple, consecutive attempts, and cumulatively offers a clinical pregnancy rate which approaches that of sIVF. The multiple pregnancy rate in nIVF is significantly reduced compared with sIVF treatment cycles. In patients over 35 years of age the benefits of nIVF were much less evident (clinical pregnancy rate: 8% per embryo transfer) and the opportunity to transfer multiple embryos in these patients seems to be advantageous.