Defining reasonable patient standard and preference for shared decision making among patients undergoing anaesthesia in Singapore.

BACKGROUND: A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. METHODS: A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients' perception of material risks, by trained interviewers. Patients' demographics were obtained. Mann-Whitney U test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. RESULTS: Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education (p < 0.007), being employed (p < 0.046) and younger age group (p < 0.003) are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea (64.8%), Drowsiness (62.4%) and Surgical Wound Pain (58.8%). Patients ranked Heart Attack (59.3%), Death (53.8%) and Stroke (52.7%) as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist (52.2%), instead of letting the doctor decide (37.1%) or deciding for themselves (10.7%). Discussion with the anaesthetist (61.3%) is the preferred medium of communication compared to reading a pamphlet (23.4%) or watching a video (15.4%). CONCLUSION: Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship.

Quantifying trace gas uptake to tropospheric aerosol: recent advances and remaining challenges.

The interactions of trace gases with tropospheric aerosol can have significant effects on both gas phase and aerosol composition. In turn, this may affect the atmospheric oxidizing capacity, aerosol hygroscopicity and optical properties, and the lifetimes of trace aerosol species. Through the detailed description of specific reaction systems, this review article illustrates how detailed experimental studies of gas-particle interactions lead to both a comprehensive understanding of the underlying physical chemistry as well as accurate parameterizations for atmospheric modeling. The reaction systems studied illustrate the complexity in the field: (i) N(2)O(5) uptake, presented as a benchmark multiphase system, can lead to both NO(x) loss and halogen activation, (ii) loss of HO(2) on aqueous particles is surprisingly poorly studied given its potential importance for HO(x) loss, (iii) uptake of HNO(3) by marine aerosol and heterogeneous oxidation of organic-bearing particles are examples of how gas-particle interactions can lead to substantial alteration of aerosol composition, and (iv) the uptake of glyoxal to ammonium sulfate aerosol leads to highly complex particle-phase chemistry. In addition, for the first time, this article presents the challenges that must be addressed in the design and interpretation of atmospheric gas-to-particle uptake experiments.

The Effects of Subjective Cognitive Decline on APOE Genotype Disclosure in the Butler Hospital Alzheimer's Prevention Registry.

BACKGROUND: Subjective cognitive decline (SCD) and APOE genotyping are both instrumental in identifying high-risk individuals for Alzheimer's disease (AD) prevention trials. OBJECTIVE: This study examined the relationship between SCD and the impact of APOE disclosure on the psychological and behavioral health of cognitively unimpaired individuals. Design/Setting/Participant: We recruited 189 trial volunteers (mean age 66, 65% female, 96% White), from the Butler Hospital Alzheimer's Prevention Registry. Participants completed screening for cognitive impairment and a psychological readiness assessment before learning their APOE genotype, and were followed for 6 months after. RESULTS: SCD had a modest, temporary impact on mood and event-related distress following APOE disclosure, specifically on those who were ε4 carriers. The presence of SCD (SCD+) did not compound the AD genetic test-specific distress related to learning that one was an ε4 carrier. SCD also did not moderate changes in perceived AD risk, with all non-carriers showing a more rapid decrease in perceived risk over time than carriers. Counterintuitively, those without SCD (SCD-) reported taking more steps in future-directives than the SCD+ group at baseline and after disclosure, potentially suggesting that those with SCD may have subtle executive declines that limit future-oriented actions or fear-avoidance behaviors. Further, the SCD- group was more accurate in recalling their APOE status and the recall accuracy correlated with their broad knowledge about APOE as a risk gene for AD. CONCLUSION: Our findings support the safety and tolerability of APOE disclosure in research volunteers regardless of their SCD statuses, but further studies are warranted to include diverse individuals and those pursuing testing through direct-to-consumer services outside of traditional research settings.

Bilateral vertebral arteries entering the C4 foramen transversarium with the left vertebral artery originating from the aortic arch.

Vertebral arteries (VAs) serve as major blood vessels to the central nervous system. VAs typically arise from the subclavian arteries and ascend separately within the transverse foramina of the cervical vertebrae (C6-C1) before entering the skull at the foramen magnum and joining at the base of the pons to form the basilar artery of the vertebrobasilar circulation. Therefore, variations in the origin and anatomic course of the VAs have implications for invasive medical procedures involving the superior thoracic/cervical regions or the cervical vertebrae. The current case report describes variation in the entry point of both VAs and the site of origin of the left vertebral artery. The variation was revealed during routine dissection of a 72-year-old female cadaver. It was found that the left vertebral artery originated directly from the aortic arch to abnormally enter the transverse foramen of C4 instead of the transverse foramen of C6. The right vertebral artery arose as usual from the right subclavian artery. However, the right vertebral artery also directly entered the transverse foramen of C4 instead of the transverse foramen of C6.

Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.

Investigation of aqueous-phase photooxidation of glyoxal and methylglyoxal by aerosol chemical ionization mass spectrometry: observation of hydroxyhydroperoxide formation.

Aqueous-phase processing of glyoxal (GLY) and methylglyoxal (MG) produces highly oxygenated, less volatile organic acids that can contribute to SOA formation and aging. In this study, aerosol chemical ionization mass spectrometry (aerosol CIMS) is employed to monitor aqueous-phase photooxidation of GLY and MG. Using iodide (I(-)) as the reagent ion, aerosol CIMS can simultaneously detect important species involved in the reactions: organic acids, peroxides, and aldehydes, so that the reconstructed total organic carbon (TOC) concentrations from aerosol CIMS data agree well with offline TOC analysis. This study also reports the first direct detection of hydroxyhydroperoxide (HHP) formation from the reaction of H(2)O(2) with GLY or MG. The formation of HHPs is observed to be reversible and an estimate of their equilibrium constants is made to be between 40 and 200 M(-1). Results of this study suggest that HHPs can form additional formic acid and acetic acid via photooxidation and regenerate GLY or MG during photooxidation, compensating their loss. HHP formation needs to be further studied for inclusion in aqueous-phase chemical models given that it may affect the aqueous partitioning of carbonyls in the atmosphere.

Burial effects of organic coatings on the heterogeneous reactivity of particle-borne benzo[a]pyrene (BaP) toward ozone.

With an aerosol flow tube coupled to an Aerodyne aerosol mass spectrometer (AMS), room temperature (296 ± 3 K) kinetics studies have been performed on the reaction of gas-phase ozone with benzo[a]pyrene (BaP) adsorbed in submonolayer amounts to dry ammonium sulfate (AS) particles. Three organic substances, i.e., bis(2-ethylhexyl)sebacate (BES, liquid), phenylsiloxane oil (PSO, liquid), and eicosane (EC, solid), were used to coat BaP-AS particles to investigate the effects of such organic coatings on the heterogeneous reactivity of PAHs toward ozone. All the reactions of particle-borne BaP with excess ozone exhibit pseudo-first-order kinetics in terms of BaP loss, and reactions with a liquid organic coating proceed by the Langmuir-Hinshelwood (L-H) mechanism. Liquid organic coatings did not significantly affect the kinetics, consistent with the ability of reactants to rapidly diffuse through the organic coating. In contrast, the heterogeneous reactivity of BaP was reduced substantially by a thin (4-8 nm), solid EC coating and entirely suppressed by thick (10-80 nm) coatings, presumably because of slow diffusion through the organic layer. Although the heterogeneous reactivity of surface-bound PAHs is extremely rapid in the atmosphere, this work is the first to experimentally demonstrate a mechanism by which the lifetime of PAHs may be significantly prolonged, permitting them to undergo long-range transport to remote locations.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Intensity modulated proton therapy treatment planning using single-field optimization: the impact of monitor unit constraints on plan quality.

PURPOSE: To investigate the effect of monitor unit (MU) constraints on the dose distribution created by intensity modulated proton therapy (IMPT) treatment planning using single-field optimization (SFO). METHODS: Ninety-four energies between 72.5 and 221.8 MeV are available for scanning beam IMPT delivery at our institution. The minimum and maximum MUs for delivering each pencil beam (spot) are 0.005 and 0.04, respectively. These MU constraints are not considered during optimization by the treatment planning system; spots are converted to deliverable MUs during postprocessing. Treatment plans for delivering uniform doses to rectangular volumes with and without MU constraints were generated for different target doses, spot spacings, spread-out Bragg peak (SOBP) widths, and ranges in a homogeneous phantom. Four prostate cancer patients were planned with and without MU constraints using different spot spacings. Rounding errors were analyzed using an in-house software tool. RESULTS: From the phantom study, the authors have found that both the number of spots that have rounding errors and the magnitude of the distortion of the dose distribution from the ideally optimized distribution increases as the field dose, spot spacing, and range decrease and as the SOBP width increases. From our study of patient plans, it is clear that as the spot spacing decreases the rounding error increases, and the dose coverage of the target volume becomes unacceptable for very small spot spacings. CONCLUSIONS: Constraints on deliverable MU for each spot could create a significant distortion from the ideally optimized dose distributions for IMPT fields using SFO. To eliminate this problem, the treatment planning system should incorporate the MU constraints in the optimization process and the delivery system should reliably delivery smaller minimum MUs.

Medication use is associated with fatigue in a sample of community-living individuals who have a spinal cord injury: a chart review.

OBJECTIVES: To investigate the relationship between medications known to cause fatigue in spinal cord injury (SCI) and fatigue severity and to describe the pattern of prescription of these medications. STUDY DESIGN: Retrospective chart review. SETTING: GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. METHODS: Medical charts of 136 individuals admitted to the GF Strong Outpatient SCI Program between December 2004 and May 2007 were reviewed. Data collected included information on medications, clinical and demographic characteristics and Fatigue Severity Scale (FSS) scores. Multiple linear regression techniques were used to analyse the data. RESULTS: Fifty-two percent of the subjects had clinically relevant fatigue. As a group, the subjects were taking 147 different medications; 41/147 medications were identified as causing fatigue. The two most commonly prescribed categories of medications were antispasticity medications (75 subjects) and analgesic medications (61 subjects). Although several variables were found to contribute to the FSS scores including the use of fatigue-causing medications, the presence of pain (7.6% of variance) and the use of fatigue-causing analgesics (4.2% of variance) explained the most variance in the scores. CONCLUSION: Fatigue is prevalent in outpatients with SCI. Fatigue-causing medications contribute to a higher FSS score. Clinicians treating persons with SCI should be aware that fatigue is a common and significant problem. Clinicians should be aware that fatigue may be exacerbated by the use of medication and should enquire about the effects of medication on fatigue when assessing and prescribing new medications.

A triggered mechanism retrieves membrane in seconds after Ca(2+)-stimulated exocytosis in single pituitary cells.

In neuroendocrine cells, cytosolic Ca2+ triggers exocytosis in tens of milliseconds, yet known pathways of endocytic membrane retrieval take minutes. To test for faster retrieval mechanisms, we have triggered short bursts of exocytosis by flash photolysis of caged Ca2+, and have tracked subsequent retrieval by measuring the plasma membrane capacitance. We find that a limited amount of membrane can be retrieved with a time constant of 4 s at 21-26 degrees C, and that this occurs partially via structures larger than coated vesicles. This novel mechanism may be arrested at a late step. Incomplete retrieval structures then remain on the cell surface for minutes until the consequences of a renewed increase in cytosolic [Ca2+] disconnect them from the cell surface in < 1 s. Our results provide evidence for a rapid, triggered membrane retrieval pathway in excitable cells.

Australian desert mice: independence of exogenous water.

Certain Australian desert mice can survive and may gain weight on a diet of dry seed without drinking water. Urine concentrations for two of the three species studied are the highest recorded for mammals. The kidneys appear to be the major avenue of water conservation.

Cocoon surrounding desert-dwelling frogs.

A cocoon formed from a single cell layer of shed stratum corneum may reduce water loss from the skin of desert-dwelling frogs while these aestivate in soil-filled burrows. In several Australian examples, the cocoon is a single layer of cells, and thus differs from the multilayered structure obtained from an American species, Scaphiopus couchi.

CDC25 phosphatases as potential human oncogenes.

Cyclin-dependent kinases (CDKs) are activated by CDC25 phosphatases, which remove inhibitory phosphate from tyrosine and threonine residues. In human cells, CDC25 proteins are encoded by a multigene family, consisting of CDC25A, CDC25B, and CDC25C. In rodent cells, human CDC25A or CDC25B but not CDC25C phosphatases cooperate with either Ha-RASG12V or loss of RB1 in oncogenic focus formation. Such transformants were highly aneuploid, grew in soft agar, and formed high-grade tumors in nude mice. Overexpression of CDC25B was detected in 32 percent of human primary breast cancers tested. The CDC25 phosphatases may contribute to the development of human cancer.

A low affinity Ca2+ receptor controls the final steps in peptide secretion from pituitary melanotrophs.

Using flash photolysis of caged Ca2+ and the membrane capacitance to monitor exocytosis, we have studied the response of single melanotrophs to a step rise in cytosolic Ca2+ concentration ([Ca2+]i). Exocytosis begins with a rapid burst. This burst is followed by a slower phase, which is inhibited at cytosolic pH 6.2, and an ultraslow phase, which is strongly temperature sensitive. The exocytic burst starts with a delay of 6-11 ms and continues at a rate that grows steeply with [Ca2+]i and is half-maximal at [Ca2+]i = 27 microM. At least 3 Ca2+ ions are required to trigger exocytosis. The rate constant at saturating [Ca2+]i suggests that exocytosis of a dense core vesicle takes 40 ms after all Ca2+ ions have bound to their regulatory sites. If docked dense core vesicles cause the exocytic burst, they must decorate the plasma membrane at a mean density of 0.5/micron2.

Properties of the fusion pore that forms during exocytosis of a mast cell secretory vesicle.

During exocytosis, secretory vesicles of mast cells generate a current transient that marks the opening of the fusion pore, the first aqueous connection that forms between the vesicle lumen and the cell exterior. By recording and analyzing such current transients, we have tracked the conductance of the fusion pore over the first millisecond of its existence. The first opening of the pore occurs rapidly, generally within 100 microseconds at 23 degrees C. The electric conductance of the pore is a few hundred picosiemens at first, but gradually increases over the subsequent milliseconds. Evidently the pore opens abruptly and then dilates. The initial conductance of the pore suggests a diameter comparable to that of a large ion channel. From an analysis of "capacitance flicker" we infer that a pore can increase its diameter severalfold and still close again completely. This suggests that several early events in membrane fusion are reversible.

Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas.

BACKGROUND: Aberrations of the p53 gene (also known as TP53) frequently lead to the synthesis of mutant proteins that accumulate in the nuclei and/or cytoplasm of neoplastic cells. Intracellular p53 protein accumulation may be an unfavorable prognostic parameter in breast, lung, ovarian, gastric, and colorectal cancers. Specific classes of p53 gene mutations, assayed by characteristic subcellular p53 protein accumulation patterns, may be useful prognostic indicators. PURPOSE: The prognostic value of nuclear and cytoplasmic p53 protein accumulation in the tumor cells of patients with colorectal carcinoma was studied. METHODS: Antibodies PAb 1801 and CM1 were used for immunocytochemical assay of nuclear and cytoplasmic p53 protein accumulation in a retrospective series of colorectal carcinoma samples obtained from 206 patients who were followed for at least 5 years. Results were correlated with the following clinicopathologic parameters: patient sex and age; tumor site, stage, and grade; and DNA ploidy status of the tumors. Overall survival and disease-free survival were analyzed with the Kaplan-Meier method. Differences in distributions were analyzed using the Mantel-Cox method. Multivariate analysis was performed with the Cox proportional hazards model. RESULTS: Immunostaining with PAb 1801 revealed nuclear p53 accumulation in 46% (95) of 206 cases, whereas CM1 immunostaining of 197 cases showed nuclear and cytoplasmic p53 accumulation in 33% (65 cases) and 50% (99 cases) of the cases, respectively. In univariate analysis, both nuclear p53PAb 1801 and cytoplasmic p53CM1 protein accumulations were significantly associated with poor overall survival (P = .0198 and P = .0017, respectively) and with disease-free survival (P = .004 and P = .0016, respectively). When patients were analyzed according to site of their tumors, nuclear p53PAb 1801 protein accumulation was statistically significant only in the right colon (P = .027), whereas cytoplasmic p53CM1 protein accumulation was statistically significant in the left colon and rectum (P = .0016). In multivariate analysis, only cytoplasmic p53CM1 protein accumulation was associated with poor overall survival and with disease-free survival (P = .006 and P = .002, respectively). With the addition of DNA ploidy status, however, cytoplasmic p53CM1 protein accumulation remained significant only for disease-free survival (P = .035). In patients with tumors of the left colon and rectum, cytoplasmic p53CM1 protein accumulation was the most significant prognostic indicator for overall survival (P = .007) and disease-free survival (P = .002) after disease stage. CONCLUSION: Cytoplasmic p53CM1 protein accumulation, but not nuclear p53PAb 1801 protein accumulation, is an independent prognostic parameter in patients with colorectal carcinomas. IMPLICATIONS: Cytoplasmic p53CM1 accumulation may be a useful indicator of patients at high risk for disease recurrence who may benefit from aggressive adjuvant therapy.

Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations.

Angiogenesis is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of prognostic value in several types of malignancies. Scarce data are available on angiogenesis in gastrointestinal tumors. We studied 36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation. Endothelial cells were immunostained with an anti-CD31 mAb; in each case three microscopic fields (x 200) with the highest number of microvessels were counted: the average value of the three fields was used to evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41 cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001; adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with metastases, disease stage, and patient survival. The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis. MVD, however, does not provide significant prognostic information in colorectal cancer patients.

Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.

The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI-absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast.