Health-care workers' understanding of and barriers to palliative care services to Aboriginal children with cancer.

AIM: To identify barriers in the understanding and provision of optimal palliative care to Aboriginal children with cancer by health-care staff, with the aim to support education and training that highlights the importance of cultural, physical and spiritual needs at end-of-life. METHODS: Medical and nursing staff working in Departments of Palliative Care, Metabolic Medicine and Haematology/Oncology at the Women's and Children's Hospital in Adelaide, South Australia, were asked to complete a survey regarding their experience in treating Aboriginal children receiving palliative care. The survey addressed the understanding of cultural and spiritual needs, barriers encountered and opinions for improved services. RESULTS: The survey was completed by 34 participants. 91.2% (n = 31) had provided care to Aboriginal children who were receiving care during palliative and end-of-life phases for a diagnosis of cancer, 58.8% (n = 20) of which had supported children returning home. Only 23.5% of participants reported comfort in communicating about spiritual/cultural needs with patients and families. There was minimal previous exposure to education (17.6%), yet all participants were interested in future education opportunities. CONCLUSION: This study highlights a paucity in understanding and comfort among health-care workers in treating Aboriginal children at end-of-life. New models, including the training of staff, educational resources and involvement of Aboriginal health-care workers, may improve care.

Stress Regulation as a Link between Executive Function and Pre-Frailty in Older Adults.

OBJECTIVES: Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues' model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults. DESIGN: Cross-sectional. SETTING: Academic general clinical research centers. PARTICIPANTS: 690 community-dwelling older adults ≥ 50 years of age. MEASUREMENTS: Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality). RESULTS: 396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, pre-frail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship. CONCLUSION: Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty.

BRCA1 and BRCA2 mutations and the risk for colorectal cancer.

Women who carry a BRCA1 or BRCA2 mutation are at high risk of breast and ovarian cancer, and may be at moderately increased risk of other cancer types. This review examines studies to date that have evaluated the risk of BRCA1 and BRCA2 mutations for colorectal cancer. Accurate knowledge of colorectal cancer risk in BRCA1/2 carriers is important, because colonoscopy screening can prevent colorectal cancer through the removal of adenomatous polyps. Most studies that have identified an increased risk for colorectal cancer in BRCA1/2 mutation carriers were in high-risk cancer families, while studies that found no association were conducted in specific populations and involved the analysis of founder mutations. A recent prospective study of 7015 women with a BRCA1 or BRCA2 mutation identified significant fivefold increased risk of colorectal cancer among BRCA1 mutation carriers younger than 50 years [standardized incidence ratio (SIR): 4.8; 95% CI: 2.2-9], but not in women with a BRCA2 mutation or in older women. Based on this evidence, women with BRCA1 mutations should be counseled about their increased risk for early-onset colorectal cancer, and offered colonoscopy at 3- to 5-year intervals between the ages of 40 and 50 years, and should follow population guidelines thereafter.

Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from a follow-up study.

BACKGROUND: The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes. METHODS: We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries. RESULTS: Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above. CONCLUSION: The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women.

Modes of delivery of genetic testing services and the uptake of cancer risk management strategies in BRCA1 and BRCA2 carriers.

BRCA testing services are now offered by various healthcare providers, thus it is important to evaluate whether the implementation of cancer risk management (CRM) strategies varies by service provider. Using a registry-based sample of 795 female BRCA mutation carriers, we explored the association between uptake of CRM strategies with duration of genetic counseling (GC) sessions, provider type, and other demographic and clinical variables. All participants completed a baseline questionnaire. Information about uptake of CRM strategies was collected for a subset of 438 participants who completed additional questions. Summary statistics and Pearson chi-squared analysis were used to examine the associations between demographic and clinical variables with service delivery factors and with the uptake of various CRM strategies. Overall uptake of CRM strategies was high across all provider types. However, GC sessions were longer when provided by a genetics professional than by another provider (p < 0.001). Furthermore, higher frequencies of uptake of most CRM strategies were associated with longer GC sessions and when testing was performed by a genetics professional. Identification of factors to optimize delivery of these specialized GC services is important to maximize implementation of CRM strategies in BRCA carriers.

Shaping the evanescent field of optical nanofibers for cold atom trapping.

We investigate trapping geometries for cold, neutral atoms that can be created in the evanescent field of a tapered optical fibre by combining the fundamental mode with one of the next lowest possible modes, namely the HE(21) mode. Counter propagating red-detuned HE(21) modes are combined with a blue-detuned HE(11) fundamental mode to form a potential in the shape of four intertwined spirals. By changing the polarization from circular to linear in each of the two counter-propagating HE(21) modes simultaneously the 4-helix configuration can be transformed into a lattice configuration. The modification to the 4-helix configuration due to unwanted excitation of the the TE(01) and TM(01) modes is also discussed.

Optical trapping using cascade conical refraction of light.

Cascade conical refraction occurs when a beam of light travels through two or more biaxial crystals arranged in series. The output beam can be altered by varying the relative azimuthal orientation of the two biaxial crystals. For two identical crystals, in general the output beam comprises a ring beam with a spot at its centre. The relative intensities of the spot and ring can be controlled by varying the azimuthal angle between the refracted cones formed in each crystal. We have used this beam arrangement to trap one microsphere within the central spot and a second microsphere on the ring. Using linearly polarized light, we can rotate the microsphere on the ring with respect to the central sphere. Finally, using a half wave-plate between the two crystals, we can create a unique beam profile that has two intensity peaks on the ring, and thereby trap two microspheres on diametrically opposite points on the ring and rotate them around the central sphere. Such a versatile optical trap should find application in optical trapping setups.

Conical diffraction of a Gaussian beam with a two crystal cascade.

Internal conical diffraction by biaxial crystals with aligned optic axes, known as cascade conical diffraction is investigated. Formulae giving the intensity distributions for a cascade conically diffracted Gaussian beam are shown to compare well with experiment for the cases of two biaxial crystals with the same and different lengths and with the second crystal rotated with respect to the first. The effects of placing half wave-plates between crystals are also investigated.

Generation of a radially polarized light beam using internal conical diffraction.

Using a combination of internal conical diffraction and Mach-Zehnder interferometry we have theoretically and experimentally demonstrated an efficient new technique for the conversion of a linearly polarized Gaussian laser beam to one with radial polarization. These methods that can be adapted to yield either ring-shaped or first order Bessel beams which are radially polarized.

The creation and annihilation of optical vortices using cascade conical diffraction.

Internal conical diffraction produces a superposition of orthogonally polarised zero- and first-order Bessel like beams from an incident circularly polarised Gaussian beam. For right-circularly polarised light, the first-order beam has an optical vortex of charge -1. Upon propagation of the first-order beam through a second biaxial crystal, a process which is termed cascade conical refraction, the generated beam is a superposition of orthogonally polarised fields of charge 0 and -1 or 0 and -2. This spin to orbital angular momentum conversion provides a new method for the generation and annihilation of optical vortices in an all-optical arrangement that is solely dependent on the incident polarisation and vortex handedness.

Generation of continuously tunable fractional optical orbital angular momentum using internal conical diffraction.

When a left-circularly polarised Gaussian light beam, which has spin angular momentum (SAM) J(sp) = sigmah = 1h per photon, is incident along one of the optic axes of a slab of biaxial crystal it undergoes internal conical diffraction and propagates as a hollow cone of light in the crystal. The emergent beam is a superposition of equal amplitude zero and first order Bessel like beams. The zero order beam is left-circularly polarised with zero orbital angular momentum (OAM) J(orb) = [see text]h = 0, while the first order beam is right-circularly polarized but carries OAM of J(orb) = 1h per photon. Thus, taken together the two beams have zero SAM and J(orb) = (1/2)h per photon. In this paper we examine internal conical diffraction of an elliptically polarised beam, which has fractional SAM, and demonstrate an all-optical process for the generation light beams with fractional OAM up to +/- 1h.

In-depth imaging and quantification of degenerative changes associated with Achilles ruptured tendons by polarization-sensitive optical coherence tomography.

The objective of this study was to develop a method based on polarization-sensitive optical coherent tomography (PSOCT) for the imaging and quantification of degenerative changes associated with Achilles tendon rupture. Ex vivo PSOCT examinations were performed in 24 patients. The study involved samples from 14 ruptured Achilles tendons, 4 tendinopathic Achilles tendons and 6 patellar tendons (collected during total knee replacement) as non-ruptured controls. The samples were imaged in both intensity and phase retardation modes within 24 h after surgery, and birefringence was quantified. The samples were fixed and processed for histology immediately after imaging. Slides were assessed twice in a blind manner to provide a semi-quantitative histological score of degeneration. In-depth micro structural imaging was demonstrated. Collagen disorganization and high cellularity were observable by PSOCT as the main markers associated with pathological features. Quantitative assessment of birefringence and penetration depth found significant differences between non-ruptured and ruptured tendons. Microstructure abnormalities were observed in the microstructure of two out of four tendinopathic samples. PSOCT has the potential to explore in situ and in-depth pathological change associated with Achilles tendon rupture, and could help to delineate abnormalities in tendinopathic samples in vivo.

Extra-pulmonary small cell carcinoma of the neopharynx: case report and review of neopharyngeal tumours after total laryngectomy.

OBJECTIVE: We report the first documented case in the world literature of primary extra-pulmonary small cell carcinoma occurring in the neopharynx following laryngectomy. METHOD: We present a case report and a review of the world literature regarding the management of tumours of the neopharynx and extra-pulmonary small cell carcinoma. RESULTS: The paucity of cases of extra-pulmonary small cell carcinoma has resulted in many departments managing this neoplasm similarly to pulmonary small cell cancer. However, the site of the primary can have an impact on disease survival and treatment options. CONCLUSION: Neopharyngeal small cell carcinoma has not previously been reported. It should be managed in the same way as other extra-pulmonary small cell carcinomas occurring within the pharynx or larynx, with combined multi-drug chemotherapy and radiotherapy. Surgery has a limited role due to the aggressiveness of the disease and the high risk of local and distant spread at presentation.

Conical diffraction of linearly polarised light controls the angular position of a microscopic object.

Conical diffraction of linearly polarised light in a biaxial crystal produces a beam with a crescent-shaped intensity profile. Rotation of the plane of polarisation produces the unique effect of spatially moving the crescent-shaped beam around a ring. We use this effect to trap microspheres and white blood cells and to position them at any angular position on the ring. Continuous motion around the circle is also demonstrated. This crescent beam does not require an interferometeric arrangement to form it, nor does it carry optical angular momentum. The ability to spatially locate a beam and an associated trapped object simply by varying the polarisation of light suggests that this optical process should find application in the manipulation and actuation of micro- and nano-scale physical and biological objects.

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.

BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations. CONCLUSION: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

Conical diffraction and Bessel beam formation with a high optical quality biaxial crystal.

The manipulation of a Gaussian laser beam using conical diffraction in a high optical quality biaxial crystal of KGd(WO(4))(2) has been examined in detail with emphasis on the experimental techniques involved and intuitive explanations of the notable features. Two different optical arrangements were used to form the Pogendorff double-ring light pattern in the focal image plane. The formation of both diverging and non-diverging zeroth and first order Bessel beams was investigated. The various intensity distributions and polarization properties were measured and compared with the predictions of well-established theory.

Pseudotumour of the temporal bone: an unusual [corrected] cause of otorrhoea and facial palsy.

An inflammatory pseudotumour of the temporal bone is a rare, idiopathic, fibro-inflammatory lesion which mimics malignancy. Although such a lesion is known to occur elsewhere in the body such as the liver, abdominal viscera, pelvis, thorax and the upper respiratory tract, the involvement of the temporal bone is extremely unusual. We present such a case in a 60-year-old man, which provided a great diagnostic challenge. We review the key radiological and histological results that confirmed the diagnosis and demonstrated for the first time that oral steroids alone may completely resolve the condition.

Classification of BRCA1 missense variants of unknown clinical significance.

BACKGROUND: BRCA1 is a tumour suppressor with pleiotropic actions. Germline mutations in BRCA1 are responsible for a large proportion of breast-ovarian cancer families. Several missense variants have been identified throughout the gene but because of lack of information about their impact on the function of BRCA1, predictive testing is not always informative. Classification of missense variants into deleterious/high risk or neutral/low clinical significance is essential to identify individuals at risk. OBJECTIVE: To investigate a panel of missense variants. METHODS AND RESULTS: The panel was investigated in a comprehensive framework that included (1) a functional assay based on transcription activation; (2) segregation analysis and a method of using incomplete pedigree data to calculate the odds of causality; (3) a method based on interspecific sequence variation. It was shown that the transcriptional activation assay could be used as a test to characterise mutations in the carboxy-terminus region of BRCA1 encompassing residues 1396-1863. Thirteen missense variants (H1402Y, L1407P, H1421Y, S1512I, M1628T, M1628V, T1685I, G1706A, T1720A, A1752P, G1788V, V1809F, and W1837R) were specifically investigated. CONCLUSIONS: While individual classification schemes for BRCA1 alleles still present limitations, a combination of several methods provides a more powerful way of identifying variants that are causally linked to a high risk of breast and ovarian cancer. The framework presented here brings these variants nearer to clinical applicability.