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In the indoor environment, occupants are exposed to air pollutants originating from continuous indoor sources and exchange with the outdoor air, with the highest concentration episodes dominated by activities performed indoors such as cooking and cleaning. Here we use the INdoor CHEMical model in Python (INCHEM-Py) constrained by measurements from the House Observations of Microbial and Environmental Chemistry (HOMEChem) campaign, to investigate the impact of a bleach cleaning event and cooking on indoor air chemistry. Measurements of the concentrations of longer-lived organic and inorganic compounds, as well as measured photolysis rates, have been used as input for the model, and the modelled hydroxyl (OH) radicals, hydroperoxyl radicals, and nitrous acid (HONO) concentrations compared to the measured values. The peak modelled OH, , and HONO concentrations during cooking and cleaning activities are about 30%, 10%, and 30% higher than the observations, respectively, within experimental uncertainties. We have determined rates for the rapid loss of HONO formed through cooking activities onto a wet surface during the cleaning events and also for the subsequent slow release of HONO from the cleaned surface back into the gas-phase. Using INCHEM-Py we have also predicted peak concentrations of chlorine (Cl) atoms, (0.75-2.3) × 10 5 atom per cm 3 at the time of cleaning. Model predictions of the Cl atom and OH radical reactivities were also explored, showing high Cl atom reactivity throughout the day, peaking around 5000-9000 s -1 . The OH reactivity was found to increase from a background value close to urban outdoor levels of 20-40 s -1 , to levels exceeding observations in outdoor polluted areas following cooking and cleaning activities (up to 160 s -1 ). This underlines the high oxidation capacity of the indoor atmospheric environment through determining the abundance of volatile organic compounds.

Individuals who work in medication-assisted treatment (MAT) programs that serve justice-involved populations face challenging conditions that can cause elevated levels of stress. Although some studies focus on stress faced by MAT professionals, few examine their coping mechanisms. This study applies the Mayo Clinic's "4A's" of stress management-accept, adapt, avoid, and alter-to better understand ways medical staff working in MAT programs manage stress. The research team used NVivo software to analyze original qualitative data from 83 MAT employees servicing justice-involved populations. The 4A's framework successfully applies to the MAT employee context. Specifically, respondents relied on the stress management techniques accept and adapt more often than avoid and alter . Descriptive demographic trends were found in the data, including Black females most often reporting they accept and adapt to stress at work. In contrast, White females chose acceptance over other management tactics, although they also reported avoidance more than other groups. MAT organizations should empower employees to amend stressors to improve personal and professional outcomes. Future studies should use qualitative and quantitative methods to examine stress in industries with compounding stressors, such as MAT professionals working in justice settings.

Indoor sources of air pollution, such as from cooking and cleaning, play a key role in indoor gas-phase chemistry. The focus of the impact of these activities on air quality tends to be indoors, with less attention given to the impact on air quality outside buildings. This study uses the INdoor CHEmical Model in Python (INCHEM-Py) and the Advanced Dispersion Modelling System (ADMS) to quantify the impact cooking and cleaning have on indoor and outdoor air quality for an idealised street of houses. INCHEM-Py has been developed to determine the concentrations of 106 indoor volatile organic compounds at the point they leave a building (defined as near-field concentrations). For a simulated 140 m long street with 10 equi-distant houses undertaking cooking and cleaning activities, the maximum downwind concentration of acetaldehyde increases from a background value of 0.1 ppb to 0.9 ppb post-cooking, whilst the maximum downwind chloroform concentrations increase from 1.2 to 6.2 ppt after cleaning. Although emissions to outdoors are higher when cooking and cleaning happen indoors, the contribution of these activities to total UK emissions of volatile organic compounds is low (less than 1%), and comprise about a quarter of those emitted from traffic across the UK. It is important to quantify these emissions, particularly as continued vehicle technology improvements lead to lower direct emissions outdoors, making indoor emissions relatively more important. Understanding how indoor pollution can affect outdoor environments, will allow better mitigation measures to be designed in the future that can take into account all sources of pollution that contribute to human exposure.

Tebentafusp is a first-in-class immunotherapy agent that comprises an engineered T-cell receptor targeting a gp100 epitope presented by human leukocyte antigen-A*02:01 cells, fused to an anti-CD3 single-chain variable fragment. Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). This review article will focus on the clinical development of tebentafusp, the mechanism of action and resultant evolution of the management of advanced UM., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Correctional officers are critical members of the prison community. However, scholarship rarely considers how correctional officers contribute to prison outcomes instead largely focusing on importation (individual) and deprivation (organizational) factors related to the incarcerated population. This is also true regarding how scholars and practitioners approach suicide committed by incarcerated people, one of the leading causes of death in US carceral institutions. Using quantitative data from confinement facilities across the United States, this study answers the research question: What is the relationship between prison suicide rates and correctional officer gender? Results show that deprivation factors (variables related to the carceral environment) influence prison suicide. Additionally, gender diversity among correctional officers reduces the rate of prison suicide. Implications for future research and practice and limitations of the study are also discussed., (© 2023. The Author(s).)

Approximately one-third of women diagnosed with melanoma are of child-bearing age. The annual incidence of melanoma has risen steadily over the last 40 years, resulting in increasing numbers of women diagnosed with melanoma both during pregnancy, and post-partum. To date, there are no formal guidelines on the management of pregnancy associated melanoma (PAM), both early stage and metastatic. This article reviews the existing literature and provides a framework for the investigation and multidisciplinary management of PAM., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m 2 /cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m 2 /14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.

Whilst anal cancer accounts for less than 1% of all new cancer cases, incidence rates have increased by up to 70% in the last 30 years with the majority of cases driven by human papilloma virus (HPV) infection. Standard treatment for localised anal cancer is chemoradiotherapy (CRT). Localised progression is the predominant pattern of relapse but well under 50% of cases are salvaged by surgery, predominantly because confirming recurrence within post-radiation change is very challenging. Identifying cancer-associated circulating cells (CCs) in peripheral blood could offer a corroborative method of monitoring treatment efficacy and identifying relapse early. To study this, nucleated cells were isolated from the blood of patients with anal cancer prior to, during, and after CRT and processed through the Amnis ® ImageStream ® X Mk II Imaging Flow Cytometer, without prior enrichment, using Pan-cytokeratin (PCK), CD45 antibodies and making use of the DNA dye DRAQ5. Analysis was undertaken using IDEAS software to identify those cells that were PCK-positive and DRAQ5-positive as well as CD45-negative; these were designated as CCs. CCs were identified in 7 of 8 patients; range 60-876 cells per mL of blood. This first report of the successful identification of CCs in anal cancer patients raises the possibility that liquid biopsies will find a future role as a prognostic/diagnostic tool in this patient group.

The synthesis and single crystal structures of Am(iii) and Cm(iii) thiocyanate complexes are reported along with an isostructural series of lanthanide thiocyanate complexes. Because the complexes are isostructural, a comparative study of the metal-thiocyanate bonds was conducted using Raman spectroscopy indicating very similar and electrostatic metal-ligand interactions.

Glioblastoma is the most common primary malignant brain tumour. Survival is poor and improved treatment options are urgently needed. Although immunotherapies have emerged as effective treatments for a number of cancers, translation of these through to brain tumours is a distinct challenge, particularly due to the blood-brain barrier and the unique immune tumour microenvironment afforded by CNS-specific cells. This review discusses the immune system within the CNS, mechanisms of immune escape employed by glioblastoma, and the immunological effects of conventional glioblastoma treatments. Novel therapies for glioblastoma that harness the immune system and their current clinical progress are outlined, including cancer vaccines, T-cell therapies and immune checkpoint modulators.

The magnetic properties and safety of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents and stimulated research on applications for SPIONs in particle imaging and magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been limited by their rapid removal from circulation via the reticuloendothelial system (RES). We explored the possibility of extending SPION circulatory time using fucoidan, a seaweed-derived food supplement, to inhibit RES uptake. The effects of fucoidan on SPION biodistribution were evaluated using ferucarbotran, which in its pharmaceutical formulation (Resovist) targets the RES. Ferucarbotran was radiolabeled at the iron oxide core with technetium-99m ( 99m Tc; t 1/2 = 6 h) or zirconium-89 ( 89 Zr; t 1/2 = 3.3 days). Results obtained with 99m Tc-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t 1/2 slow) from 37.4 to 150 min (n = 4; P < 0.0001). To investigate whether a longer circulatory half-life could lead to concomitant increased tumor uptake, the effects of fucoidan were tested with 89 Zr-ferucarbotran in mice bearing syngeneic subcutaneous (GL261) tumors. In this model, the longer circulatory half-life achieved with fucoidan was associated with a doubling in tumor SPION uptake (n = 5; P < 0.001). Fucoidan was also effective in significantly increasing the circulatory half-life of perimag-COOH, a commercially available SPION with a larger hydrodynamic size (130 nm) than ferucarbotran (65 nm). These findings indicate successful diversion of SPIONs away from the hepatic RES and show realistic potential for future clinical applications.

Five heteroleptic Cu(i)bis(phenanthroline) chromophores with distinct variation in the steric bulk at the 2,9-phenanthroline position were synthesized using the HETPHEN method, and their ground and excited state properties are described. Analysis of the crystal structures reveals a significant distortion from tetrahedral geometry around the Cu(i) centre which is attributed to favourable aromatic interactions between the two phenanthroline ligands. Ultrafast and nanosecond transient optical spectroscopies reveal that the excited state lifetime can be tuned across two orders of magnitude up to 74 nanoseconds in acetonitrile by changing the 2,9-substituent from hydrogen to sec-butyl. X-ray transient absorption spectroscopy at the Cu K-edge confirmed Cu(i) oxidation to Cu(ii) and revealed a decrease of the Cu-N bond lengths in the excited state. The ground and excited state characterization presented here will guide the integration of CuHETPHEN chromophores into complex electron donor-acceptor architectures.

This manuscript describes a combination of DFT calculations and experiments to assess the reduction of borazines (B-N heterocycles) by η 6 -coordination to Cr(CO) 3 or [Mn(CO) 3 ] + fragments. The energy requirements for borazine reduction are established as well as the extent to which coordination of borazine to a transition metal influences hydride affinity, basicity, and subsequent reduction steps at the coordinated borazine molecule. Borazine binding to M(CO) 3 fragments decreases the thermodynamic hydricity by >30 kcal mol -1 , allowing it to easily accept a hydride. These hydricity criteria were used to guide the selection of appropriate reagents for borazine dearomatization. Reduction was achieved with an H 2 -derived hydride source, and importantly, a pathway which proceeds through a single electron reduction and H-atom transfer reaction, mediated by anthraquinone was uncovered. The latter transformation was also carried out electrochemically, at relatively positive potentials by comparison to all prior reports, thus establishing an important proof of concept for any future electrochemical B[double bond, length as m-dash]N bond reduction., (This journal is © The Royal Society of Chemistry 2015.)

The synthesis, X-ray crystal structure, vibrational and optical spectroscopy for the eight-coordinate thiocyanate compounds, [Et4 N]4 [Pu(IV) (NCS)8 ], [Et4 N]4 [Th(IV) (NCS)8 ], and [Et4 N]4 [Ce(III) (NCS)7 (H2 O)] are reported. Thiocyanate was found to rapidly reduce plutonium to Pu(III) in acidic solutions (pH<1) in the presence of NCS(-) . The optical spectrum of [Et4 N][SCN] containing Pu(III) solution was indistinguishable from that of aquated Pu(III) suggesting that inner-sphere complexation with [Et4 N][SCN] does not occur in water. However, upon concentration, the homoleptic thiocyanate complex [Et4 N]4 [Pu(IV) (NCS)8 ] was crystallized when a large excess of [Et4 N][NCS] was present. This compound, along with its U(IV) analogue, maintains inner-sphere thiocyanate coordination in acetonitrile based on the observation of intense ligand-to-metal charge-transfer bands. Spectroscopic and crystallographic data do not support the interaction of the metal orbitals with the ligand π system, but support an enhanced An(IV) -NCS interaction, as the Lewis acidity of the metal ion increases from Th to Pu., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Boron clusters are proposed as a new concept for the design of magnesium-battery electrolytes that are magnesium-battery-compatible, highly stable, and noncorrosive. A novel carborane-based electrolyte incorporating an unprecedented magnesium-centered complex anion is reported and shown to perform well as a magnesium-battery electrolyte. This finding opens a new approach towards the design of electrolytes whose likelihood of meeting the challenging design targets for magnesium-battery electrolytes is very high., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recharging spent BN fuel: {Cr(CO)(3)} mediates the reduction of borazines by hydride and methyl nucleophiles to generate anionic complexes of dearomatized hexamethylborazine. Subsequent quenching leads to the release of a substituted cyclotriborazane, successfully demonstrating the stepwise reduction of a B=N bond., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

People often face outcomes of important events that are beyond their personal control, such as when they wait for an acceptance letter, job offer, or medical test results. We suggest that when wanting and uncertainty are high and personal control is lacking, people may be more likely to help others, as if they can encourage fate's favor by doing good deeds proactively. Four experiments support this karmic-investment hypothesis. When people want an outcome over which they have little control, their donations of time and money increase (experiments 1 and 2), but their participation in other rewarding activities does not (experiment 1b). In addition, at a job fair, job seekers who feel the process is outside (vs. within) their control make more generous pledges to charities (experiment 3). Finally, karmic investments increase optimism about a desired outcome (experiment 4). We conclude by discussing the role of personal control and magical beliefs in this phenomenon.

What kinds of purchases do the most to make us happy? Previous research (Carter & Gilovich, 2010; Van Boven & Gilovich, 2003) indicates that experiences, such as vacations and concerts, are more likely to do so than material possessions, such as clothes and electronic gadgets. The present research was designed to explore 1 potential explanation for this result, namely, that experiences tend to be more closely associated with the self than possessions. The authors first show that people tend to think of their experiential purchases as more connected to the self than their possessions. Compared with their material purchases, participants drew their experiential purchases physically closer to the self (Study 1), were more likely to mention them when telling their life story (Study 2), and felt that a purchase described in terms of its experiential, rather than its material, qualities would overlap more with their sense of who they are (Study 4). Participants also felt that knowing a person's experiential purchases, compared with their material purchases, would yield greater insight into that person's true self (Studies 3A-3C). The authors then show that the tendency to cling more closely to cherished experiential memories is connected to the greater satisfaction people derive from experiences than possessions (Study 5)., (2012 APA, all rights reserved)

Objective: Traumatic life histories are highly prevalent in people living with HIV/AIDS and predict sexual risk behaviors, medication adherence, and all-cause mortality. Yet the causal pathways explaining these relationships remain poorly understood. We sought to quantify the association of trauma with negative behavioral and health outcomes and to assess whether those associations were explained by mediation through psychosocial characteristics., Methods: In 611 outpatient people living with HIV/AIDS, we tested whether trauma's influence on later health and behaviors was mediated by coping styles, self-efficacy, social support, trust in the medical system, recent stressful life events, mental health, and substance abuse., Results: In models adjusting only for sociodemographic and transmission category confounders (estimating total effects), pasttrauma exposure was associated with 7 behavioral and health outcomes including increased odds or hazard of recent unprotected sex [odds ratio (OR) = 1.17 per each additional type of trauma, 95% confidence interval = 1.07 to 1.29], medication nonadherence (OR = 1.13, 1.02 to 1.25), hospitalizations (hazard ratio = 1.12, 1.04 to 1.22), and HIV disease progression (hazard ratio = 1.10, 0.98 to 1.23). When all hypothesized mediators were included, the associations of trauma with health care utilization outcomes were reduced by about 50%, suggesting partial mediation (eg, OR for hospitalization changed from 1.12 to 1.07), whereas point estimates for behavioral and incident health outcomes remained largely unchanged, suggesting no mediation (eg, OR for unprotected sex changed from 1.17 to 1.18). Trauma remained associated with most outcomes even after adjusting for all hypothesized psychosocial mediators., Conclusions: These data suggest that past trauma influences adult health and behaviors through pathways other than the psychosocial mediators considered in this model.

There is growing clinical demand for image registration techniques that allow multimodal data fusion for accurate targeting of needle biopsy and ablative prostate cancer treatments. However, during procedures where transrectal ultrasound (TRUS) guidance is used, substantial gland deformation can occur due to TRUS probe pressure. In this paper, the ability of a statistical shape/motion model, trained using finite element simulations, to predict and compensate for this source of motion is investigated. Three-dimensional ultrasound images acquired on five patient prostates, before and after TRUS-probe-induced deformation, were registered using a nonrigid, surface-based method, and the accuracy of different deformation models compared. Registration using a statistical motion model was found to outperform alternative elastic deformation methods in terms of accuracy and robustness, and required substantially fewer target surface points to achieve a successful registration. The mean final target registration error (based on anatomical landmarks) using this method was 1.8 mm. We conclude that a statistical model of prostate deformation provides an accurate, rapid and robust means of predicting prostate deformation from sparse surface data, and is therefore well-suited to a number of interventional applications where there is a need for deformation compensation.

There is scant evidence that incidental cues in the environment significantly alter people's political judgments and behavior in a durable way. We report that a brief exposure to the American flag led to a shift toward Republican beliefs, attitudes, and voting behavior among both Republican and Democratic participants, despite their overwhelming belief that exposure to the flag would not influence their behavior. In Experiment 1, which was conducted online during the 2008 U.S. presidential election, a single exposure to an American flag resulted in a significant increase in participants' Republican voting intentions, voting behavior, political beliefs, and implicit and explicit attitudes, with some effects lasting 8 months after the exposure to the prime. In Experiment 2, we replicated the findings more than a year into the current Democratic presidential term. These results constitute the first evidence that nonconscious priming effects from exposure to a national flag can bias the citizenry toward one political party and can have considerable durability.

When it comes to spending disposable income, experiential purchases tend to make people happier than material purchases (Van Boven & Gilovich, 2003). But why are experiences more satisfying? We propose that the evaluation of experiences tends to be less comparative than that of material possessions, such that potentially invidious comparisons have less impact on satisfaction with experiences than with material possessions. Support for this contention was obtained in 8 studies. We found that participants were less satisfied with their material purchases because they were more likely to ruminate about unchosen options (Study 1); that participants tended to maximize when selecting material goods and satisfice when selecting experiences (Study 2); that participants examined unchosen material purchases more than unchosen experiential purchases (Study 3); and that, relative to experiences, participants' satisfaction with their material possessions was undermined more by comparisons to other available options (Studies 4 and 5A), to the same option at a different price (Studies 5B and 6), and to the purchases of other individuals (Study 5C). Our results suggest that experiential purchase decisions are easier to make and more conducive to well-being.

While the study of nationalism has received much attention throughout the social sciences and humanities, the experimental investigation of it lags behind. In this paper we review recent advances in the examination of implicit nationalism. In the first set of experiments we survey, the Palestinian, Israeli, Italian, and Russian flags were primed (or not, in the control conditions) and their effects on political thought and behavior were tested. In the second set the American or the Israeli flag was primed (or not) and prejudice toward African-Americans or Palestinians (respectively) was examined. The results of all experiments suggest that the implicit activation of national cues has far-reaching implications on political thought and behavior as well as on attitudes toward minorities. Under the assumption that the image of national flags is associated in memory with national ideologies, these results suggest that national ideologies can be implicitly pursued in a way that significantly affects our thoughts and behaviors.

Statistical shape modelling potentially provides a powerful tool for generating patient-specific, 3D representations of bony anatomy for computer-aided orthopaedic surgery (CAOS) without the need for a preoperative CT scan. Furthermore, freehand 3D ultrasound (US) provides a non-invasive method for digitising bone surfaces in the operating theatre that enables a much greater region to be sampled compared with conventional direct-contact (i.e., pointer-based) digitisation techniques. In this paper, we describe how these approaches can be combined to simultaneously generate and register a patient-specific model of the femur and pelvis to the patient during surgery. In our implementation, a statistical deformation model (SDM) was constructed for the femur and pelvis by performing a principal component analysis on the B-spline control points that parameterise the freeform deformations required to non-rigidly register a training set of CT scans to a carefully segmented template CT scan. The segmented template bone surface, represented by a triangulated surface mesh, is instantiated and registered to a cloud of US-derived surface points using an iterative scheme in which the weights corresponding to the first five principal modes of variation of the SDM are optimised in addition to the rigid-body parameters. The accuracy of the method was evaluated using clinically realistic data obtained on three intact human cadavers (three whole pelves and six femurs). For each bone, a high-resolution CT scan and rigid-body registration transformation, calculated using bone-implanted fiducial markers, served as the gold standard bone geometry and registration transformation, respectively. After aligning the final instantiated model and CT-derived surfaces using the iterative closest point (ICP) algorithm, the average root-mean-square distance between the surfaces was 3.5mm over the whole bone and 3.7mm in the region of surgical interest. The corresponding distances after aligning the surfaces using the marker-based registration transformation were 4.6 and 4.5mm, respectively. We conclude that despite limitations on the regions of bone accessible using US imaging, this technique has potential as a cost-effective and non-invasive method to enable surgical navigation during CAOS procedures, without the additional radiation dose associated with performing a preoperative CT scan or intraoperative fluoroscopic imaging. However, further development is required to investigate errors using error measures relevant to specific surgical procedures.

A method is presented for the rigid registration of tracked B-mode ultrasound images to a CT volume of a femur and pelvis. This registration can allow tracked surgical instruments to be aligned with the CT image or an associated preoperative plan. Our method is fully automatic and requires no manual segmentation of either the ultrasound images or the CT volume. The parameter which is directly related to the speed of sound through tissue has also been included in the registration optimisation process. Experiments have been carried out on six cadaveric femurs and three cadaveric pelves. Registration results were compared with a "gold standard" registration acquired using bone implanted fiducial markers. Results show the registration method to be accurate, on average, to 1.6 mm root-mean-square target registration error.

Intraoperative freehand three-dimensional (3-D) ultrasound (3D-US) has been proposed as a noninvasive method for registering bones to a preoperative computed tomography image or computer-generated bone model during computer-aided orthopedic surgery (CAOS). In this technique, an US probe is tracked by a 3-D position sensor and acts as a percutaneous device for localizing the bone surface. However, variations in the acoustic properties of soft tissue, such as the average speed of sound, can introduce significant errors in the bone depth estimated from US images, which limits registration accuracy. We describe a new self-calibrating approach to US-based bone registration that addresses this problem, and demonstrate its application within a standard registration scheme. Using realistic US image data acquired from 6 femurs and 3 pelves of intact human cadavers, and accurate Gold Standard registration transformations calculated using bone-implanted fiducial markers, we show that self-calibrating registration is significantly more accurate than a standard method, yielding an average root mean squared target registration error of 1.6 mm. We conclude that self-calibrating registration results in significant improvements in registration accuracy for CAOS applications over conventional approaches where calibration parameters of the 3D-US system remain fixed to values determined using a preoperative phantom-based calibration.

The deformation of soft tissue compromises the accuracy of image-guided surgery based on preoperative images, and restricts its applicability to surgery on or near bony structures. One way to overcome these limitations is to combine biomechanical models with sparse intraoperative data, in order to realistically warp the preoperative image to match the surgical situation. We detail the process of biomechanical modelling in the context of image-guided surgery. We focus in particular on the finite element method, which is shown to be a promising approach, and review the constitutive relationships which have been suggested for representing tissue during surgery. Appropriate intraoperative measurements are required to constrain the deformation, and we discuss the potential of the modalities which have been applied to this task. This technology is on the verge of transition into clinical practice, where it promises to increase the guidance accuracy and facilitate less invasive interventions. We describe here how soft tissue modelling techniques have been applied to image-guided surgery applications.

We describe a new self-calibrating approach to rigid registration of 3D ultrasound images in which in vivo data acquired for registration are used to simultaneously perform a patient-specific update of the calibration parameters of the 3D ultrasound system. Using a self-calibrating implementation of a point-based registration algorithm, and points obtained from ultrasound images of the femurs and pelves of human cadavers, we show that the accuracy of registration to a CT scan is significantly improved compared with a standard algorithm. This new approach provides an effective means of compensating for errors introduced by the propagation of ultrasound through soft tissue, which currently limit the accuracy of conventional methods where the calibration parameters are fixed to values determined preoperatively using a phantom.

A method is presented for the registration of tracked B-mode ultrasound images to a CT volume of a femur or pelvis. This registration can allow tracked surgical instruments to be aligned with the CT image or an associated preoperative plan. Our method requires no manual segmentation of either the ultrasound images or the CT volume. The CT and US images are processed to produce images where the image intensity represents the probability of the presence of a bone edge. These images are then registered together using normalised cross-correlation as a similarity measure. The parameter which represents the speed of sound through tissue has also been included in the registration optimisation process. Experiments have been carried out on six cadaveric femurs and three cadaveric pelves. Registration results were compared with a "gold standard" registration acquired using bone implanted fiducial markers. Results show the registration method to be accurate, on average, to 1.7 mm root-mean-square target registration error.

Activation of presynaptic gamma-aminobutyric acid type B (GABA(B)) receptors inhibits neurotransmitter release at many synapses (both excitatory and inhibitory), and activation of postsynaptic GABA(B) receptors leads to a general inhibition of the postsynaptic cell in mature neurons. Although the action of GABA(B) receptors at the soma of excitatory hippocampal pyramidal cells has been resolved to be regulation of a potassium or calcium conductance, it is not clear that all neurons in the hippocampus demonstrate similar effects of GABA(B) receptor activation. In the current study, GABA(B) receptor-mediated effects on calcium currents in acute cultures composed of heterogeneous cells from the superior region of neonatal hippocampi were studied. In 54.5% of cells, the GABA(B) receptor agonist baclofen (10 microM) attenuated the whole-cell calcium current by 21.0% +/- 1.1%. In 29.9% of cells, baclofen facilitated the calcium current by 43.5% +/- 8.1%. The component of current attenuated by baclofen was blocked by the N-type calcium channel antagonist omega-conotoxin GVIA (3 microM). The component of current facilitated by baclofen was blocked by the L-type channel antagonist nimodipine (20 microM). For cells that showed calcium current facilitation, baclofen shifted the half-maximal activation by approximately -14 mV. The data indicate that activation of GABA(B) receptors in neurons of the superior hippocampus attenuates current through N-type channels and facilitates current through L-type channels. The two opposing effects of GABA(B) receptor activation may reflect the heterogeneity of the cultured cells or may be a developmentally regulated phenomenon., (Copyright 2004 Wiley-Liss, Inc.)

Encapsulation of Amberlyst A-26 supported tribromide in a 10,000 MW polyethylene glycol matrix gives a robust colour-sensitive reagent matrix which can be deposited on indium-tin oxide coated polyvinylidene fluoride (PVDF) piezoelectric film for the detection of styrene (and other alkene) vapours.

We evaluated the variability in the amount of protein adsorbed onto the surface of individual wells of an assortment of microtitre plates by use of procedures involving enzyme-protein conjugates. Coefficients of variation in adsorbed protein ranged from 5.2 to 29.5%. Microtitre plates show a distinct "edge effect"; wells at the edges of a plate adsorb more protein than those in the interior, which markedly affects results from immunoassays involving such plates. In a sandwich enzyme immunoassay the results for an individual sample varied by +/- 18%; in a competitive assay, values read from different calibration curves in the same plate varied by +/- 11%. Scanning electron microscopy and birefringence studies demonstrated no marked physical differences between individual wells on a plate. The variability in the amount of protein adsorbed onto the surface of individual wells on the same microtitre plate seriously affects the reliability and interpretation of results of immunoassays in which such plates are used as solid supports.

The limited stability of immobilised enzymes is a major factor restricting their use in clinical chemistry. The immobilisation procedure described here affords a simple method of enhancing the stability of certain enzymes immobilised on nylon. Studies with alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase have indicated that a significant increase in stability can be obtained using this immobilisation procedure as compared with conventional procedures. As anticipated the immobilisation procedure was unsatisfactory for oxidases such as glucose oxidase.

In this study of a normal population from a Midland factory, obesity showed a direct relationship to serum triglyceride and cholesterol levels in males but not in females. High-density lipoprotein (HDL) cholesterol and apolipoprotein A1 levels were not related to obesity in either sex. Alcohol consumption was associated with increased serum triglyceride levels in males but not in females and serum HDL cholesterol levels were also higher in male drinkers only. Cigarette smoking was associated with increased serum triglyceride levels in both sexes but HDL cholesterol levels were reduced only in female smokers. Apolipoprotein A1 levels were not related to smoking in females.

High-density lipoprotein (HDL) cholesterol levels were decreased in patients with non-insulin dependent diabetes at diagnosis when matched with a control population for sex, age, obesity, alcohol consumption and cigarette smoking. There was no association between serum HDL-cholesterol concentration and the percentage of glycosylated haemoglobin A1 (HbA1). Serum HDL-cholesterol levels were lower in diabetics over the whole range of serum triglyceride levels, and particularly in hyper-triglyceridaemic diabetics. Serum apolipoprotein A-I levels were not decreased in diabetics with normal serum triglyceride levels, so that the ratio of HDL-cholesterol to apolipoprotein A-I was significantly decreased in diabetics (p Less Than 0.005). Decreased HDL-cholesterol levels in non-insulin dependent diabetes could be relevant to the subsequent development of atherosclerosis.

A method has been developed for the rapid determination of substances by use of solid-phase reagents and a luminescence indicator reaction coupled with photographic detection of the light. The viability of the assay has been demonstrated for glucose estimations. The method uses small sample sizes (5-20 mul) and shows good sensitivity, e.g., detection of glucose down to 28 nmole.

Effective internal quality control and external quality assessment of high-density lipoprotein cholesterol assay is made difficult by analyte instability, and the suitability of quality-control sera for this purpose has not been studied. We have therefore investigated the properties of 25 different control sera from 15 suppliers by estimating within-batch precision for the two precipitation procedures used most widely (phosphotungstate/Mg2+ and heparin/Mn2+ with enzymic measurement of cholesterol. Some sera had properties similar to those of fresh human serum, but others demonstrated poor precision for one or both procedures or contained apparent high-density lipoprotein cholesterol in unphysiological concentrations. A study of six sera indicated that between-batch precision was consistent with the within-batch findings. We found that eight of the 25 batches of quality-control serum we investigated may be used for internal quality control and external quality assessment of high-density lipoprotein cholesterol assay.

Thermal studies of various types of microtitre plate have shown that wells at the edges of a plate have different thermal characteristics from those in the centre. This may contribute to the 'edge effect' observed when such plates are used as solid supports for protein immunobilisation in immunoassays.

The electrophoretic procedure for high density lipoprotein cholesterol determination recently introduced by Corning Medical has been assessed. The results corrrelated well with those obtained by phosphotungstate/Mg precipitation and ultracentrifuge procedures, but the between-batch CV was 6% in the clinically important range below 1 mmol/l. The densitometer, which must be carefully aligned before use for this analysis, seemed sensitive to variations in the plates and patterns produced. The technique required that great care, especially with timing, and appeared expensive.

The various types of chemiluminescent and bioluminescent reactions are described. Applications of luminescence in the analysis of substancs of clinical interest are surveyed. The advantages, disadvantages, and prospects for luminescent assays are discussed.