Temporal bone borehole accuracy for cochlear implantation influenced by drilling strategy: an in vitro study

Purpose

Minimally invasive cochlear implantation is a surgical technique which requires drilling a canal from the mastoid surface toward the basal turn of the cochlea. The choice of an appropriate drilling strategy is hypothesized to have significant influence on the achievable targeting accuracy. Therefore, a method is presented to analyze the contribution of the drilling process and drilling tool to the targeting error isolated from other error sources.

Methods

The experimental setup to evaluate the borehole accuracy comprises a drill handpiece attached to a linear slide as well as a highly accurate coordinate measuring machine (CMM). Based on the specific requirements of the minimally invasive cochlear access, three drilling strategies, mainly characterized by different drill tools, are derived. The strategies are evaluated by drilling into synthetic temporal bone substitutes containing air-filled cavities to simulate mastoid cells. Deviations from the desired drill trajectories are determined based on measurements using the CMM.

Results

Using the experimental setup, a total of 144 holes were drilled for accuracy evaluation. Errors resulting from the drilling process depend on the specific geometry of the tool as well as the angle at which the drill contacts the bone surface. Furthermore, there is a risk of the drill bit deflecting due to synthetic mastoid cells.

Conclusions

A single-flute gun drill combined with a pilot drill of the same diameter provided the best results for simulated minimally invasive cochlear implantation, based on an experimental method that may be used for testing further drilling process improvements.     

Molecular orientation sensitive second harmonic microscopy by radially and azimuthally polarized light

We demonstrate the possibility to switch the z-polarization component of the illumination in the vicinity of the focus of high-NA objective lenses by applying radially and azimuthally polarized incident light. The influence of the field distribution on nonlinear effects was first investigated by the means of simulations. These were performed for high-NA objective lenses commonly used in nonlinear microscopy. Special attention is paid to the influence of the polarization of the incoming field. For linearly, circularly and radially polarized light a considerable polarization component in z-direction is generated by high NA focusing. Azimuthal polarization is an exceptional case: even for strong focusing no z-component arises. Furthermore, the influence of the input polarization on the intensity contributing to the nonlinear signal generation was computed. No distinct difference between comparable input polarization states was found for chosen thresholds of nonlinear signal generation. Differences in signal generation for radially and azimuthally polarized vortex beams were experimentally evaluated in native collagen tissue (porcine cornea). The findings are in good agreement with the theoretical predictions and display the possibility to probe the molecular orientation along the optical axis of samples with known nonlinear properties. The combination of simulations regarding the nonlinear response of materials and experiments with different sample orientations and present or non present z-polarization could help to increase the understanding of nonlinear signal formation in yet unstudied materials.OCIS codes: (000.3860) Mathematical methods in physics, (180.4315) Nonlinear microscopy, (190.0190) Nonlinear optics, (190.2620) Harmonic generation and mixing, (190.4975) Parametric processes, (260.5430) Polarization     

Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.     

Suppression of hypoxia-inducible factor-1α contributes to the antiangiogenic activity of red propolis polyphenols in human endothelial cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1α (HIF1α) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent manner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1α protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1α protein half-life from ~58 min to 38 min under hypoxic conditions. The reduced HIF1α protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1α. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1α. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1α protein accumulation and signaling.     

Self-Reported Experience of Racial Discrimination and Health Care Use in New Zealand: Results From the 2006/07 New Zealand Health Survey

Objectives. We investigated whether reported experience of racial discrimination in health care and in other domains was associated with cancer screening and negative health care experiences.Methods. We used 2006/07 New Zealand Health Survey data (n = 12 488 adults). We used logistic regression to examine the relationship of reported experience of racial discrimination in health care (unfair treatment by a health professional) and in other domains (personal attack, unfair treatment in work and when gaining housing) to breast and cervical cancer screening and negative patient experiences adjusted for other variables.Results. Racial discrimination by a health professional was associated with lower odds of breast (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.14, 0.996) and cervical cancer (OR = 0.51; 95% CI = 0.30, 0.87) screening among Maori women. Racial discrimination by a health professional (OR = 1.57; 95% CI = 1.15, 2.14) and racial discrimination more widely (OR = 1.55; 95% CI = 1.35, 1.79) were associated with negative patient experiences for all participants.Conclusions. Experience of racial discrimination in both health care and other settings may influence health care use and experiences of care and is a potential pathway to poor health.Racism is increasingly recognized as an important determinant of health and driver of ethnic health inequalities.1 Regardless of its health effects, racism breaches fundamental human rights and is morally wrong. It is important to understand how racism operates as a health risk to develop interventions that reduce ethnic inequalities in health within a context of eliminating racism.2Racism is an organized system that categorizes racial/ethnic groups and structures opportunity, leading to inequities in societal goods and resources and a racialized social order.3–5 Racism operates via institutional and individual practices (racial discrimination) and varies in form and type.6,7 The pathways whereby racism leads to poor health are also multiple, with direct and indirect mechanisms such as race-based assaults and violence, physiological and psychological stress mechanisms, differential exposures to health risk factors, differential access to and experiences of health care, and differential access to goods, resources, and power in society.6,8–10Research on racism and health, particularly self-reported racism, has increased. Self-reported experience of racism has been linked to multiple health measures (including mental and physical health outcomes and health risk factors) across a variety of countries and for different ethnic groups.10–12 Research on how self-reported experience of racism may negatively affect health has largely focused on racism as a stressor with mental and physical health consequences.10,13 Comparatively less evidence is available on how experience of racism may influence health service use,10 although this is another potentially important pathway to poor health.14,15Studies on the association between self-reported racism and health care experience and use have included racism experienced within the health care system, outside of the health care system, or both.16–19 Health care measures have included use of specific services such as cancer screening19–24 and receipt of optimal care,20,25 measures of unmet need,16,26 measures of adherence to care,17,27,28 and measures of satisfaction and experiences with care.18,29–31Various mechanisms have been suggested to explain how the experience of racism may negatively affect health care use, experiences of health care, and subsequent poor health. Experiences of racism within the health care system may influence health by shaping decision making of both providers and patients and influencing future health behaviors, including future health care use behaviors and potential disengagement from the health care system.14,18,26 Experiences of racism in wider society also may lead to general mistrust and avoidance of dominant culture institutions, including health care systems.15,30 This is supported by evidence that both experiences of racism and general discrimination within and outside of health care have been associated with negative health care use measures.15,16,19,22New Zealand has a population of approximately 4.4 million people, with the major ethnic groupings being Maori (indigenous peoples, 15% of the population), European (77%), Pacific (7%), and Asian (10%).32 Ethnic inequalities in health and socioeconomic status persist, with racism a potentially important contributor to these inequalities.33 Previous research in New Zealand has shown reported experience of racial discrimination by a health professional to be higher among non-European ethnic groups with experiences of racial discrimination in different settings associated with multiple health outcomes and risk factors.34In this study, we focused on the relationship between racial discrimination and health service use and experience, an area not previously examined in New Zealand. We provide important information on how racial discrimination may affect health care use as a possible pathway to poor health outcomes and ethnic health inequalities in New Zealand. In addition, our study contributes to the limited evidence on racial discrimination and health care internationally.Primary health care in New Zealand is available to all residents and is usually provided at general practices. Costs of visits are universally subsidized by government to enable lower patient copayments with additional limited provision for extra funding based on high need.35 Currently, 2 publicly funded national cancer screening programs are available.36 Breast cancer screening is free to all eligible women through BreastScreen Aotearoa. Cervical cancer screening usually incurs a fee and is available through patients’ usual primary care provider or specific cervical cancer screening providers.We specifically examined the association between self-reported experience of racial discrimination and the use of health care in 2 domains—cancer screening and negative patient perceptions of health care encounters. We hypothesized that experience of racial discrimination both within and outside the health care system may negatively affect how individuals use and experience health care.     

Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study

Background

Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010–2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010–2011 TIV safety and immunogenicity in children 12–59 months of age to inform public health decision making.

Methods

Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009–10 TIV, received 1 or 2 doses of 2010–11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ∼24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621.

Results

Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5 °C) was more common in two-dose compared to one dose recipients (16.7%, n = 4 v. 1.0%, n = 2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p < 0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident.

Conclusions

Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero-protected for A/H1N1 after receipt of the 2010–11 TIV.     

The pervasive effects of racism: experiences of racial discrimination in New Zealand over time and associations with multiple health domains

Self-reported experience of racial discrimination has been linked to a range of health outcomes in various countries and for different ethnic groups. This study builds on previous work in New Zealand to further investigate the prevalence of self-reported experience of racial discrimination by ethnicity, changes over time and associations with multiple health measures. The study uses data from the 2002/03 (n=12,500) and 2006/07 (n=12,488) New Zealand Health Surveys, nationally representative population-based surveys of adults (15+ years). Reported experience of racial discrimination was measured in both surveys and covered 5 items: experience of an ethnically motivated physical or verbal attack; and unfair treatment because of ethnicity by a health professional, in work, or when gaining housing. Ethnicity was classified as Maori, Pacific, Asian or European. Health indicators included measures of: mental health (SF36 mental health scale, psychological distress, doctor diagnosed mental health condition); physical health (self-rated health, SF36 physical functioning scale, cardiovascular disease); and health risk (smoking, hazardous drinking, excess body fat). Logistic regression was used to examine changes in prevalence of reported experience of racial discrimination over time and associations with health. Reported experience of racial discrimination increased between 2002/03 (28.1% ever) and 2006/07 (35.0% ever) among Asian peoples but remained largely unchanged for other ethnic groupings (Maori 29.5%, Pacific 23.0%, European 13.5%). Experience of racial discrimination was associated with all negative health measures except excess body fat. Where there were significant associations, a dose-response relationship was also evident. We conclude that racial discrimination experienced across a range of settings has the potential to impact on a wide range of health outcomes and risk factors. While ongoing research is needed to understand the multifarious nature of racism and the pathways by which it leads to poor health, it is feasible to monitor experiences of racial discrimination in national surveys.     

Altered Resting State Connectivity of the Insular Cortex in Individuals With Fibromyalgia

The insular cortex (IC) and cingulate cortex (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and default mode network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. We also investigated the relationship between connectivity, experimental pain, and current clinical chronic pain. Functional connectivity was assessed using resting-state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched healthy controls using predefined seed regions in the anterior, middle, and posterior IC. FM patients exhibited greater connectivity between 1) right mid IC and right mid/posterior CC and right mid IC, 2) right posterior IC and left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds.PerspectiveThese data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation, which may play a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with FM.