Wearable sensors: modalities, challenges, and prospects.

Wearable sensors have recently seen a large increase in both research and commercialization. However, success in wearable sensors has been a mix of both progress and setbacks. Most of commercial progress has been in smart adaptation of existing mechanical, electrical and optical methods of measuring the body. This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them conformal and flexible, and in the development of companion software that increases the value of the measured data. However, chemical sensing modalities have experienced greater challenges in commercial adoption, especially for non-invasive chemical sensors. There have also been significant challenges in making significant fundamental improvements to existing mechanical, electrical, and optical sensing modalities, especially in improving their specificity of detection. Many of these challenges can be understood by appreciating the body's surface (skin) as more of an information barrier than as an information source. With a deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-art for wearable sensor technology, the roadmap becomes clearer for creating the next generation of innovations and breakthroughs.

Superwetting and aptamer functionalized shrink-induced high surface area electrochemical sensors.

Electrochemical sensing is moving to the forefront of point-of-care and wearable molecular sensing technologies due to the ability to miniaturize the required equipment, a critical advantage over optical methods in this field. Electrochemical sensors that employ roughness to increase their microscopic surface area offer a strategy to combatting the loss in signal associated with the loss of macroscopic surface area upon miniaturization. A simple, low-cost method of creating such roughness has emerged with the development of shrink-induced high surface area electrodes. Building on this approach, we demonstrate here a greater than 12-fold enhancement in electrochemically active surface area over conventional electrodes of equivalent on-chip footprint areas. This two-fold improvement on previous performance is obtained via the creation of a superwetting surface condition facilitated by a dissolvable polymer coating. As a test bed to illustrate the utility of this approach, we further show that electrochemical aptamer-based sensors exhibit exceptional signal strength (signal-to-noise) and excellent signal gain (relative change in signal upon target binding) when deployed on these shrink electrodes. Indeed, the observed 330% gain we observe for a kanamycin sensor is 2-fold greater than that seen on planar gold electrodes.

Plasma free reversible and irreversible microfluidic bonding.

We demonstrate a facile, plasma free process to fabricate both reversibly and irreversibly sealed microfluidic chips using a PDMS-based adhesive polymer mixture. This is a versatile method that is compatible with current PDMS microfluidics processes. It allows for easier fabrication of multilayer microfluidic devices and is compatible with micropatterning of proteins for cell culturing. When combined with our Shrinky-Dink microfluidic prototyping, complete microfluidic device fabrication can be performed without the need for any capital equipment, making microfluidics accessible to the classroom.

Tunable optical response of bowtie nanoantenna arrays on thermoplastic substrates.

Thermally responsive polymers present an interesting avenue for tuning the optical properties of nanomaterials on their surfaces by varying their periodicity and shape using facile processing methods. Gold bowtie nanoantenna arrays are fabricated using nanosphere lithography on prestressed polyolefin (PO), a thermoplastic polymer, and optical properties are investigated via a combination of spectroscopy and electromagnetic simulations to correlate shape evolution with optical response. Geometric features of bowtie nanoantennas evolve by annealing at temperatures between 105 °C and 135 °C by releasing the degree of prestress in PO. Due to the higher modulus of Au versus PO, compressive stress occurs on Au bowtie regions on PO, which leads to surface buckling at the two highest annealing temperatures; regions with a 5 nm gap between bowtie nanoantennas are observed and the average reduction is 75%. Reflectance spectroscopy and full-wave electromagnetic simulations both demonstrate the ability to tune the plasmon resonance wavelength with a window of approximately 90 nm in the range of annealing temperatures investigated. Surface-enhanced Raman scattering measurements demonstrate that maximum enhancement is observed as the excitation wavelength approaches the plasmon resonance of Au bowtie nanoantennas. Both the size and morphology tunability offered by PO allows for customizing optical response.

Selective screening for gestational diabetes mellitus in adolescent pregnancies.

OBJECTIVE: It is unclear whether it is cost-effective to universally screen adolescent gravidas for gestational diabetes mellitus (GDM). Our objective was to identify the prevalence of gestational diabetes in our adolescent population and to review risk factors that would most easily identify a subset of adolescent patients at greatest risk for the development of gestational diabetes. METHODS: Six hundred thirty-two adolescents were identified from 11,486 deliveries in our institution through International Classification of Diseases (9th edition) codes. Eleven of those adolescents had GDM. Their charts and those of a representative group of nondiabetic adolescent gravidas were analyzed for GDM risk factors, including race/ethnicity, body mass index (BMI), family history of diabetes, other medical disorders, and previous history of GDM, macrosomia, stillbirths, or anomalous fetus. Statistical analyses used chi2 and Student t tests as appropriate. RESULTS: The prevalence of GDM among adolescent gravidas was 1.7%. No difference was identified between the adolescent pregnancies with GDM and the comparison group for race/ethnicity, family history, or presence of medical disorders. Risk factors requiring a previous obstetric history could not be evaluated adequately because of the high prevalence of nulliparas. There was a higher prevalence of BMI over 27 in adolescents with GDM (P < .001). CONCLUSION: Body mass index is an important risk factor for the development of gestational diabetes in adolescent gravidas. We recommend that selective screening for GDM of adolescent gravidas be performed on the basis of BMI.

Cutaneous angiosarcoma of the distal extremity.

A case of childhood cutaneous angiosarcoma is presented to emphasize the importance of accurate histological diagnosis in lymphovascular malformations that behave atypically and to review the natural history, aetiology, and differential diagnosis of this condition.

Nodular amyloidosis of the lung from intravenous drug abuse: an uncommon cause of multiple pulmonary nodules.

Bilateral pulmonary nodules in an immunocompromised host may offer a diagnostic dilemma. We present a case of a human immunodeficiency virus positive patient with history of intravenous drug abuse (IVDA) who was incidentally found to have bilateral multiple pulmonary nodules. She was diagnosed as having nodular pulmonary amyloidosis, presumably serum amyloid A derived (AA) in origin but confirmed not to be of amyloid light chain derived origin (AL), histologically associated with focal birefringent material and foreign body giant cell reaction, probably due to IVDA. Asymptomatic multiple pulmonary nodules in amyloidosis are usually of AL origin; however, recently similar changes have been found in the AA form in patients with Sjogren's syndrome or Crohn's disease. It has not been previously described in association with IVDA. Thus, this case documents a unique cause of bilateral pulmonary nodules due to amyloidosis consequent to IVDA.

Pancreatic inflammatory tumour: a rare entity in childhood.

Pancreatic tumours are rare childhood neoplasms. Inflammatory myofibrohistiocytic tumours (IMTs) represent an uncommon but distinct pathological subgroup that creates diagnostic and therapeutic dilemmas. We report a case of IMT arising from the body and tail of the pancreas in an 8-year-old girl presenting with a mass and abdominal pain. A locally aggressive tumour with no evidence of distant metastasis was encountered at laparotomy and resected. Pathologically, the tumour revealed a mixed inflammatory cell infiltrate with myofibrohistiocytic proliferation. These features can resemble a sarcoma. A review of the literature is provided which emphasises the clinical features, pathological findings, and management strategies for these unusual tumours. Complete surgical excision, aided by radiological surveillance, appears to offer the best guidelines for definitive management.

Ploidy analysis on Wilms' tumour touch imprints using ethidium bromide and automated image analysis integrated confocal laser scanning microscopy.

Although image analysis (IA) is increasingly being used to quantitate nuclear DNA, comparative data between fluorescence methods of IA and flow cytometry (FCM) is limited. In this study fluorescence IA was compared with FCM data in a series of Wilms' tumour touch preparations. Airdried touch imprints that had previously been Giemsa stained were restained with ethidium bromide. Confocal fluorescence images were obtained with a confocal laser scanning microscope and assessed by a fully automated IA package. Data was collected from 400 nuclei per imprint. The resulting DNA histograms were analysed and ploidy status and DNA indices determined using standard criteria. Results were compared with those derived from FCM analysis of nuclear suspensions. Ten of twelve tumours were concordant by both techniques. However in two cases assessed as diploid by FCM, IA identified aneuploidy. Excellent correlation between DNA indices as assessed by both techniques was observed (r = 0.987). In the three cases for which both unstained and Giemsa stained touch imprints were available for IA, the histogram configurations did not differ significantly. Fluorescence IA is an accurate and sensitive technique for DNA quantitation, which appears at least comparable to FCM assessment and which has a number of important advantages.

Composition of the inflammatory infiltrate in pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans): a prospective, comparative immunophenotyping study.

Dermatopathological evaluation of pediatric preputial inflammatory disease rarely allows for specific diagnosis other than pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans, LSA/BXO). A prospective immunopathological study was performed on 20 consecutive, unselected, clinically and histopathologically confirmed LSA/BXO cases to determine the relative presence of T and B lymphocytes. There were seven cases with early stages of disease, eight with florid disease, and five with later stages of disease. Two ritual circumcision specimens and 12 specimens with non-LSA/BXO balanitis, collected during the same period, were used as controls. The infiltrate in LSA/BXO patients was wholly composed of T cells (positive with UCLH-1 antibody) in all cases. B cells (positive with L-26 antibody) were found only focally in small, discreet, easily recognizable (follicular or early follicle-like) aggregates, positioned slightly deeper than the band-like infiltrate of T cells. T cells were inconspicuous in 9 of the 12 control specimens. In the three other controls, T cells were much more obvious and these patients showed clinical features possibly suggestive of LSA/BXO in early, prediagnosable phases of development. We conclude that limited immunophenotyping may be a useful adjunct to diagnosis in pediatric cases in which only limited tissue is available or the disease may be more difficult to classify with confidence.

Analysis of relative proliferation rates of Wilms' tumor components using proliferating cell nuclear antigen and MIB-1 (Ki-67 equivalent antigen) immunostaining and assessment of mitotic index.

BACKGROUND: Flow-cytometric analysis of proliferation index (PI) has potential use in predicting prognosis in malignancy. Its relevance to heterogeneous tumors has not been conclusively studied. In nephroblastoma, where the epithelial components are considered more differentiated than others, potentially different PIs may exist within a single lesion based on the inverse relation between differentiation and proliferation. Proliferating cell nuclear antigen (PCNA) and MIB-1 (Ki-67 equivalent antigen) demonstration in histologic sections by immunoperoxidase methods may allow for determination of PI in relation to tissue type. EXPERIMENTAL DESIGN: A consecutive unselected series of 8 pediatric nephroblastoma patients was used to study the relation between PI and histologic differentiation as established by flow-cytometric analysis of nuclear suspensions prepared from formalin-fixed and paraffin-embedded tissue and by PCNA/MIB1 staining of parallel histologic sections. PI by PCNA/MIB1 was established using 5-microns paraffin sections, immunoperoxidase, and quantification procedures detailed in the literature. The mitotic index (MI) of tissue components was separately assessed using 5-microns hematoxylin and eosin-stained sections and counting procedures detailed in the literature. RESULTS: The 8 lesions showed a PI of 4 to 20% as determined by flow cytometry. Using PCNA staining, the epithelium showed a mean PI of 55.5% (range 40 to 80%), that was significantly higher (p < 0.001, Wilcoxon's two-tailed rank sum test) than blastema (mean PI: 34.1%, range 17.5 to 76.5%) and stroma (mean PI of 14.9%, range 5 to 24%, p < 0.001, Wilcoxon's two-tailed rank sum test). Although, probably due to tissue antigen preservation, acceptable MIB-1 staining was not achieved in all lesions (5 of 8), the results, although generally with lower labeling indices, confirmed the PCNA findings. The relative MI of epithelial components was higher than that of stroma and blastema in keeping with the immunocytochemical findings. In 6 of 8 cases, the PI by flow-cytometric analysis was lower than the lowest value for the PI (labeling index) of an individual tissue type found by PCNA or MIB staining. CONCLUSIONS: The differences found between PI of the different tissue components in nephroblastoma are difficult to understand if the epithelial components (with the highest PI values) are considered as differentiation products from the other components of the lesion. The relation between PIs as determined by PCNA/MIB-1 analysis/mitotic index, for the three components and the PI as established by flow cytometry is not simply explained by the relative volume of the tissue components.

Scalp cyst with heterotopic brain tissue.

A multilocular scalp lesion was noticed at birth in a female infant. There was no underlying skull defect. Histological examination revealed neural tissue staining with S-100 and GFAP, but not with a neurofilament stain, which is in keeping with a glial cell origin. Heterotopic brain tissue is a rare developmental abnormality, which usually has no effect on neurological development. It should be considered in the differential diagnosis of scalp lesions in neonates.

A rare congenital intranasal polyp: mesenchymal chondrosarcoma of the nasal region.

A mesenchymal chondrosarcoma of the nasal region in a neonate is described. Problems of histological interpretation and management are discussed.

Primary malignant tumor of the aorta.

Primary malignant tumors of the aorta are extremely rare. Review of the literature indicates that there are only 21 recorded cases of primary malignant tumors of the aorta. The purpose of this article is to record an additional case of primary malignant tumor of the aorta.

The effect of splenectomy on antibody response to lipopolysaccharide (E. coli) immunization.

The influence of splenectomy on the antibody response to lipopolysaccharide (LPS: E. coli 0128:B12) was investigated in mice. Splenectomy had little effect on the primary response to the LPS. However, the level of IgG anti-LPS antibodies of splenectomized mice was significantly lower than that of sham-operated mice when the mice were immunized 1, 3, and 7 days after the operation and reimmunized 7 days after the first immunization. There was no significant difference in those immunized 30 days after the operation and reimmunized 7 days later. In mice immunized before splenectomy and reimmunized 30 days after splenectomy, the level of IgG anti-LPS antibodies was low, even in the mice splenectomized 30 days after primary immunization. Our results indicate that splenectomy impairs the antibody response to lipopolysaccharides.