THz Bragg structures fabricated with additive manufacturing.

The advancement of THz science and technology is desirable to facilitate the application of THz technologies in many sectors. Specialized THz photonic elements for these applications require desirable absorption and refractive characteristics in the THz regime. THz photonic elements can be created with additive manufacturing, and specifically 3D printing, forgoing the need for complex fabrication procedures and methodologies. Such THz photonic elements include periodic Bragg structures, which are capable of filtering specific THz frequencies. The authors present a THz Bragg structure fabricated with 3D printing via fused filament fabrication. The THz Bragg structure is made from high-impact polystyrene filament material, which is characterized in this paper with THz time-domain spectroscopy. The geometry and theoretical operation of the THz Bragg structure is investigated with finite-difference time-domain electromagnetic simulations. The THz Bragg structure is evaluated using a THz experimental test bed. There is agreement between the theoretical and the experimental filtering placement within the frequency domain for the THz Bragg structure. The capability of tunable frequency filtering of the presented THz Bragg structure, fabricated with 3D printing, is established and facilitates future advancements in applications of THz science and technology.

Psychiatric and psychosocial characteristics of suicide completers: A 13-year comprehensive evaluation of psychiatric case records and postmortem findings.

Currently, there are limited data comparing demographic and clinical characteristics of individuals who died by probable suicide and who did and did not previously attend mental health services (MHSs). This study compared demographic and clinical factors for both groups, in a Western region of Ireland over a 13-year period. Postmortem reports between January 1, 2006 and March 31, 2019 were reviewed for 400 individuals who died by probable suicide. Relevant sociodemographic and clinical data were extracted from individuals' lifetime case notes. One hundred and fifty nine individuals (40%) had attended MHSs at some stage ("attendee"). Hanging was the most common method of suicide (61%), followed by drowning (18%) for both attendees and nonattendees of MHSs, with more violent methods utilized overall by nonattendees (p = 0.028). Sixty-eight percent of individuals who previously attempted hanging subsequently died utilizing this method. A higher proportion of attendees were female compared to nonattendees of MHSs (28.9 vs. 14.5%, p = 0.001). Recurrent depressive disorder (55%) was the most common diagnosed mental health disorder. For individuals with a diagnosis of schizophrenia, 39% had antipsychotic medications detectable in their toxicology reports. In conclusion, the majority of people who died by probable suicide had never had contact with MHSs, and nonattendees overall were more likely to utilize violent methods of suicide. Nonconcordance with psychotropic medications in psychotic patients and previous hanging attempt were highlighted as potential risk factors for death by probable suicide.

Searching for meaning is associated with costly prosociality.

The study of meaning in life has largely centered on its relationship with personal well-being, while a focus on how meaning is related to enhancing the well-being of others has received less research attention. Although searching for meaning may imply lower personal well-being, we find that meaning-seekers are more motivated to perform costly prosocial actions for the sake of others' well-being, given the perceived meaningfulness of these behaviors. Studies 1-4 (N = 780) show that meaning-seeking correlates with the motivation to engage in a range of costly prosocial behaviors. Meaning-seeking is further shown to be distinct from pursuing happiness in its relationship with costly prosociality (Study 2 & 3) and to share a stronger association with high-cost than low-cost prosociality (Study 3 & 4). Study 5 (N = 370; pre-registered) further shows that the search for meaning is related to costly prosocial behavior in the recent past. While our studies are cross-sectional, the pattern of findings suggests that seeking meaning (rather than happiness) may play an important role in motivating altruistic tendencies.

Prescribing vegetarian or flexitarian diets leads to sustained reduction in meat intake.

Many people agree that reducing the consumption of meat has good ends (e.g., for animal welfare, the environment, and human health). However, the question of which advocacy strategies are most effective in enabling wide-spread meat reduction remains open. We explored this by prescribing four different meat reduction diets to omnivorous participants for a seven-day adherence period, and studied their meat consumption over time. The diets included a Vegetarian diet, and three flexitarian diets (Climatarian - limit beef and lamb consumption; One Step for Animals - eliminate chicken consumption; Reducetarian - reduce all meat consumption). Results showed pronounced differences between groups in meat consumption during the adherence period, where the Vegetarian group ate significantly less meat than the flexitarian groups. All groups decreased their meat intake in the weeks following the adherence period compared to baseline, however, there were no significant group differences in the level of decrease over time. Participants also changed their attitudes toward meat and animals from pre-to post-intervention, and decreases in commitment toward and rationalization of meat-eating partially mediated change in meat intake. These findings reveal that the diet assignments had some impact on participants' meat consumption and attitudes even after the prescribed adherence period had ended. However, the sustained decrease in consumption did not vary depending on what meat reduction strategy was originally used.

Comparison of nonlinear filtering techniques for photonic systems with blackbody radiation.

This work explores a theoretical solution for noise reduction in photonic systems using blackbody radiators. Traditionally, signal noise can be reduced by increasing the integration time during signal acquisition. However, increasing the integration time during signal acquisition will reduce the acquisition speed of the signal. By developing and applying a filter using a model based on the theoretical equations for blackbody radiation, the noise of the signal can be reduced without increasing integration time. In this work, three filters, extended Kalman filter, unscented Kalman filter (UKF), and extended sliding innovation filter (ESIF), are compared for blackbody photonic systems. The filters are tested on a simulated signal from five scenarios, each simulating different experimental conditions. In particular, the nonlinear filters, UKF and ESIF, showed a significant reduction of noise from the simulated signal in each scenario. The results show great promise for photonic systems using blackbody radiators that require post-process for noise reduction.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18-30), or low-risk (0-17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Leukocyte Tetraspanin CD53 Restrains α3 Integrin Mobilization and Facilitates Cytoskeletal Remodeling and Transmigration in Mice.

The importance of tetraspanin proteins in regulating migration has been demonstrated in many diverse cellular systems. However, the function of the leukocyte-restricted tetraspanin CD53 remains obscure. We therefore hypothesized that CD53 plays a role in regulating leukocyte recruitment and tested this hypothesis by examining responses of CD53-deficient mice to a range of inflammatory stimuli. Deletion of CD53 significantly reduced neutrophil recruitment to the acutely inflamed peritoneal cavity. Intravital microscopy revealed that in response to several inflammatory and chemotactic stimuli, absence of CD53 had only minor effects on leukocyte rolling and adhesion in postcapillary venules. In contrast, Cd53-/- mice showed a defect in leukocyte transmigration induced by TNF, CXCL1 and CCL2, and a reduced capacity for leukocyte retention on the endothelial surface under shear flow. Comparison of adhesion molecule expression in wild-type and Cd53-/- neutrophils revealed no alteration in expression of ß2 integrins, whereas L-selectin was almost completely absent from Cd53-/- neutrophils. In addition, Cd53-/- neutrophils showed defects in activation-induced cytoskeletal remodeling and translocation to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased α3 integrin expression. These alterations were associated with effects on inflammation, so that in Cd53-/- mice, the onset of neutrophil-dependent serum-induced arthritis was delayed. Together, these findings demonstrate a role for tetraspanin CD53 in promotion of neutrophil transendothelial migration and inflammation, associated with CD53-mediated regulation of L-selectin expression, attachment to the endothelial surface, integrin expression and trafficking, and cytoskeletal function.

Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression.

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53-/- mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53-/- B cells and reduced stability of L-selectin on Cd53-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Characterisation of graphene electrodes for microsystems and microfluidic devices.

Fabrication of microsystems is traditionally achieved with photolithography. However, this fabrication technique can be expensive and non-ideal for integration with microfluidic systems. As such, graphene fabrication is explored as an alternative. This graphene fabrication can be achieved with graphite oxide undergoing optical exposure, using optical disc drives, to impose specified patterns and convert to graphene. This work characterises such a graphene fabrication, and provides fabrication, electrical, microfluidic, and scanning electron microscopy (SEM) characterisations. In the fabrication characterisation, a comparison is performed between traditional photolithography fabrication and the new graphene fabrication. (Graphene fabrication details are also provided.) Here, the minimum achievable feature size is identified and graphene fabrication is found to compare favourably with traditional photolithography fabrication. In the electrical characterisation, the resistivity of graphene is measured as a function of fabrication dose in the optical disc drive and saturation effects are noted. In the microfluidic characterisation, the wetting properties of graphene are shown through an investigation of the contact angle of a microdroplet positioned on a surface that is treated with varying fabrication dose. In the SEM characterisation, the observed effects in the previous characterisations are attributed to chemical or physical effects through measurement of SEM energy dispersive X-ray spectra and SEM images, respectively. Overall, graphene fabrication is revealed to be a viable option for development of microsystems and microfluidics.

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Trampoline-related injuries in children: a preliminary biomechanical model of multiple users.

BACKGROUND: The recent popularity of domestic trampolines has seen a corresponding increase in injured children. Most injuries happen on the trampoline mat when there are multiple users present. This study sought to examine and simulate the forces and energy transferred to a child's limbs when trampolining with another person of greater mass. METHODS: The study used a computational biomechanical model. RESULTS: The simulation demonstrated that when two masses bounce out of phase on a trampoline, a transfer of kinetic energy from the larger mass to the smaller mass is likely to occur. It predicted that when an 80 kg adult is on a trampoline with a 25 kg child, the energy transfer is equivalent to the child falling 2.8 m onto a solid surface. Additionally, the rate of loading on the child's bones and ligaments is greater than that on the accompanying adult. CONCLUSIONS: Current guidelines are clear that more than one user on a trampoline at a time is a risk factor for serious injury; however, the majority of injuries happen in this scenario. The model predicted that there are high energy transfers resulting in serious fracture and ligamentous injuries to children and that this could be equated to equivalent fall heights. This provides a clear take-home message, which can be conveyed to parents to reduce the incidence of trampoline-related injuries.

Insulin increases H2O2-induced pancreatic beta cell death.

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (ß) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic ß cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic ß-cells. Cell death was induced by treatment with H(2)O(2), and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H(2)O(2) increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic ß cells and increased the effect of H(2)O(2). These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H(2)O(2) and, perhaps, other inducers of apoptosis.

The significance of tumour cell immunophenotype in myeloma and its impact on clinical outcome.

BACKGROUND AND AIMS: Antigen expression of multiple myeloma (MM) cells is heterogeneous. We have investigated the clinical impact of expression of some of the commonly used immunohistochemical markers in the diagnostic work-up of bone marrow trephine biopsy (BMTB) samples in MM. PATIENTS AND METHODS: BMTB samples from 107 MM patients who had received an autologous stem cell transplant (ASCT) following chemotherapy were evaluated. In 75 cases, the immunophenotype had been evaluated on two or more occasions on further follow-up. RESULTS: In the cases evaluated, 32%, 79%, 73%, 39% and 60% of cases had been scored positive for CD20, CD79a, CD56, cyclin D1 and epithelial membrane antigen (EMA) respectively. Absence of CD79a was predictive of poor overall survival (OS) from the time of transplant (p = 0.029) and poor event-free survival (EFS) from the time of transplant (p = 0.003). Absence of EMA (p = 0.02) was predictive of poor EFS from the time of diagnosis. Presence of CD56 was predictive of poor EFS from the time of diagnosis (p = 0.026). On multivariate analysis, only CD79a expression (OS and EFS from the time of transplant) and EMA expression (EFS from the time of diagnosis) maintained their significance. 13 of 75 patients showed an immunophenotypic drift during the disease course. Loss of CD20 (four cases) during the disease course in cases that were previously scored positive correlated with significant worsening both, of OS (p = 0.02) and EFS (p = 0.009) from the time of diagnosis. CONCLUSION: Immunophenotype impacts on clinical outcome in MM.

Vascular proliferations of the breast.

Vascular proliferations of the breast are uncommon but potentially diagnostically challenging lesions. Clinically apparent processes are more likely to be malignant; however, a range of benign entities which must be differentiated from angiosarcoma also exists. This review discusses first, breast lesions of apparent vascular origin, then benign and histologically bland perilobular, cavernous and capillary haemangiomas. Subsequently, more diagnostically challenging, atypical haemangiomas, papillary endothelial hyperplasia, angiomatosis and angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) are considered. In addition, lesions with low-grade malignant potential such as haemangiopericytomas and epithelioid haemangioendotheliomas may rarely present in the breast. However, primary angiosarcomas and radiation-associated vascular lesions are reviewed in depth, as these entities are of greatest clinical and pathological significance.

Morphologically distinct patterns of apoptosis correlate with size and high-grade dysplasia in colonic adenomas.

AIMS: To examine the relationship of morphological patterns of apoptosis in colonic adenomas to standard pathological variables. METHODS AND RESULTS: Apoptosis patterns were evaluated in 184 consecutive colonic adenomas and 14 adenocarcinomas, using haematoxylin and eosin sections. Apoptosis identification was selectively validated by electron microscopy. There were three patterns of apoptosis: (i) confluent basal apoptosis; (ii) crypt lumen apoptosis, both assessed semiquantitatively; and (iii) scattered apoptosis (not quantified). Adenoma site, size, type, mitoses, and grade of dysplasia were also assessed. MIB-1 immunostaining was performed in 20 cases. In 142 adenomas (77%) confluent basal apoptosis (n = 124) and/or crypt lumen apoptosis (n = 69) were identified; 42 (23%) had scattered apoptosis only. Significant correlations were: (i) extensive confluent basal apoptosis with small adenomas < or =5 mm (P < 0.0001); (ii) crypt lumen apoptosis with large adenomas >5 mm (P < 0.0001) and (iii) with high-grade dysplasia (P < 0.0003); and (iv) coexistence of both patterns (n = 51) with large adenomas >5 mm (P < 0.0001). Neither apoptosis pattern correlated with other variables. Adenocarcinomas had minimal confluent basal apoptosis (5/14), conspicuous crypt lumen apoptosis (14/14), intraglandular coagulative necrosis, and scattered apoptotic tumour cells. CONCLUSIONS: Confluent basal apoptosis is maximal early in colonic tumorigenesis. The 'switch' to a predominant crypt lumen apoptosis pattern suggests that a different apoptosis induction mechanism might be associated with the transition to adenocarcinoma.

Clinicopathological significance of Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded.

During a recent discussion on classification of cervical cytology, the introduction of a 'Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded' (BNCH) category was proposed. BNCH cases diagnosed prospectively were retrieved from laboratory records. Questionnaires were sent to referring practitioners regarding clinicopathological outcome. Cytopathological features resulting in the BNCH classification were recorded on slide review. A total of 103 reports on conventional cervical smears diagnosed as BNCH from 1999 to 2002 were retrieved, comprising 0.096% of 107 634 smears. Of 86/103 cases with clinical follow-up, CIN2 or worse was present in 30 (35%); 15 (17%) showed a borderline/low-grade abnormality and 41 (48%) were negative. No individual cytopathological feature was predictive of high-grade disease on follow-up. The yield of high-grade abnormalities on follow-up of BNCH supports the introduction of this terminology.

Regulation of cell apoptosis by protein kinase c delta.

The isoforms of the PKC family are activated in response to mitogenic stimuli, to inflammatory stimuli, and to stress and play important roles in a variety of cellular functions including apoptosis. PKCdelta a member of the novel PKC subfamily, is actively involved in cell apoptosis in a stimulus and tissue specific manner; it both regulates the expression and function of apoptotic related proteins and is itself a target for caspases. Activation of PKCdelta by various apoptotic stimuli results in the translocation of PKCdelta to distinct cellular compartments such as mitochondria, golgi and nucleus, and the differential translocation contributes to its different effects. In addition, phosphorylation of PKCdelta on distinct tyrosine residues and its association with specific apoptotic related proteins such as c-Abl, DNA-PK, p73 and lamin B are pivotal to its function in cell apoptosis. Recent findings on these aspects of the PKCdelta cascades are the major focus of this review.

vFLIP protects PC-12 cells from apoptosis induced by Sindbis virus: implications for the role of TNF-alpha.

Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor alpha (TNF-alpha), and pre-treatment of the cells with an anti-TNF-alpha blocking antibody or with soluble TNF-alpha receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-alpha R1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-alpha plays an important role in the apoptotic response.