Singular phase nano-optics in plasmonic metamaterials for label-free single-molecule detection.

The non-trivial behaviour of phase is crucial for many important physical phenomena, such as, for example, the Aharonov-Bohm effect and the Berry phase. By manipulating the phase of light one can create 'twisted' photons, vortex knots and dislocations which has led to the emergence of the field of singular optics relying on abrupt phase changes. Here we demonstrate the feasibility of singular visible-light nano-optics which exploits the benefits of both plasmonic field enhancement and the peculiarities of the phase of light. We show that properly designed plasmonic metamaterials exhibit topologically protected zero reflection yielding to sharp phase changes nearby, which can be employed to radically improve the sensitivity of detectors based on plasmon resonances. By using reversible hydrogenation of graphene and binding of streptavidin-biotin, we demonstrate an areal mass sensitivity at a level of fg mm(-2) and detection of individual biomolecules, respectively. Our proof-of-concept results offer a route towards simple and scalable single-molecule label-free biosensing technologies.

Patients with diabetic nephropathy on renal replacement therapy in England and Wales.

BACKGROUND: The incidence of patients with diabetic nephropathy (DN) who start renal replacement therapy (RRT) is increasing. AIM: To describe the characteristics and survival of patients with DN starting RRT in the UK. DESIGN: Retrospective cohort study. METHODS: We analysed data for incident patients on RRT in centres participating in the Renal Association UK Renal Registry (UKRR), 1997 -2004, comparing DN vs. non-DN patients with regard to survival, social deprivation, ethnicity, gender, and age, using Cox regression models. RESULTS: DN was the most common renal disease (19%) in the 20 532 patients starting RRT. The majority of patients with DN (77%) were Caucasian. Within the Caucasian population, DN patients were more likely to be from a socially deprived area (p < 0.0001). About 20% were referred <3 months before starting RRT. The difference in crude survival was greatest in younger patients (5-year survival was 56% (DN) vs. 85% (non-DN) in patients aged 18-54 years, and 17% (DN) vs. 28% (non-DN) in patients aged >or=65 years). Despite adjusting for gender, age, treatment modality, social deprivation, referral and co-morbidities, the long-term prognosis for DN patients aged 18-54 years was worse (adjusted hazard ratio 2.13, 95%CI 1.23-3.67) than for older age groups. DISCUSSION: Patients with DN starting RRT are more likely to come from socially deprived areas. Relative risk of death is greatest in working-age DN patients and is not fully explained by recorded co-morbidity. This emphasizes the need for focused diabetes care in poorer areas, and assessment of quality of care of diabetic patients on RRT.

Equity of access to dialysis facilities in Wales.

BACKGROUND: Demand for dialysis, particularly, in-centre haemodialysis (HD), is growing, and more units will be needed. Travel time to treatment is consistently a major area of concern for patients. AIM: To analyse access to current dialysis facilities in Wales, and use the data to help plan for new dialysis units. METHODS: We analysed a combination of UK Renal Registry, Welsh population census data, the Welsh Index of Multiple Deprivation 2005 (WIMD), travel time and geographical information systems. RESULTS: Prevalence of HD fell significantly with increasing travel time from units. This was not influenced by the WIMD. Prior to the opening of a new HD unit in Aberystwyth, prevalence in the surrounding area was significantly lower than for Wales as whole, but within 2 years, prevalence had risen to approximate national levels. In Haverfordwest, an area >30 min drive from any current facility, prevalence is consistently and significantly lower than for Wales as a whole, and has not shown the growth seen elsewhere in the country. DISCUSSION: The ability to combine data has enabled modelling of the likely immediate impact of opening a new unit in Haverfordwest, and also provided an estimate of its required capacity. This multidisciplinary approach to demand analysis should help to highlight areas of under-provision, and facilitate the planning of the sites and sizes of new dialysis units in Wales.

Current chronic kidney disease practice patterns in the UK: a national survey.

BACKGROUND: There is an increasing focus on improving the detection and management of patients with chronic kidney disease (CKD). Data on CKD prevalence based on population sampling are now available, but there are few data about CKD patients attending nephrology services or how such services are organized. AIM: To survey services for CKD patients nationally. METHODS: A pre-piloted questionnaire was sent to all 72 renal units in the UK, referring to the situation in June 2004. RESULTS: Seventy units (97%) responded. The median ratio of prevalent CKD patients/prevalent renal replacement therapy (RRT) patients in the 25 units with data was 3.7 (IQR 2.7-5.7) and the median ratio of CKD stage 4 and 5 patients/prevalent RRT patients was 0.6 (IQR 0.4-1.1). This gives an estimated 140 000 CKD patients under the care of UK nephrologists, with 23 000 at CKD stage 4 or 5 (excluding those on RRT). Very few units had a full complement of the recommended multi-skilled renal team. Counsellors and psychologist were the most common perceived shortages. Of 70 responding units, 50 (74%) were using low clearance clinics for management of advanced CKD patients. Elective dialysis access services often had long delays, with median waiting time for vascular access ranging between 1 and 36 weeks, and for Tenchkoff catheter, between 0 and 12 weeks. DISCUSSION: CKD patients are a significant workload for UK nephrologists. Current provision of service is variable, and services need to be re-designed to cope with the expected future increase of referral of CKD patients.

Trends in adult renal replacement therapy in the UK: 1982-2002.

BACKGROUND: Following the introduction of dialysis and transplantation for the treatment of established renal failure (ERF) 40 years ago, the UK failed to match the achievements of many other countries. AIM: To review progress with treatment for ERF in the UK in the past 20 years. DESIGN: Review of four cross-sectional national studies, and 1997-2002 annual UK Renal Registry data. METHODS: Data on UK patients on renal replacement treatment (RRT) were collated from three sources: European Registry reports for 1982-1990, surveys carried out within the UK in 1993, 1996, 1998 and 2002, and the UK Renal Registry database (1997-2002). Trends in acceptance and prevalence rates, median age, cause of ERF, and treatment modality were analysed and compared with current data from other countries. RESULTS: The UK annual acceptance rate for RRT increased from 20 per million population (pmp) in 1982 to 101 pmp in 2002. This growth was largely in those aged over 65 years, and in those with co-morbidity. Annual acceptance rates for ERF due to diabetes rose from 1.6 to 18 pmp. The prevalence of RRT increased from 157 pmp in 1982 to 626 pmp in 2002. Hospital haemodialysis has become the main modality, and is increasingly being provided in satellite units. Although rising, UK acceptance and prevalence rates are still lower than in many developed countries. DISCUSSION: Despite significant expansion in RRT services for adults in the UK over the last 20 years, there is evidence of unmet need, and need is expected to rise, due to demographic changes and trends in type 2 diabetes. Continuing growth in the already substantial investment in RRT will be needed, unless efforts to prevent the occurrence of ERF are successful.

Hybrid graphene plasmonic waveguide modulators.

The unique optical and electronic properties of graphene make possible the fabrication of novel optoelectronic devices. One of the most exciting graphene characteristics is the tunability by gating which allows one to realize active optical devices. While several types of graphene-based photonic modulators have already been demonstrated, the potential of combining the versatility of graphene with subwavelength field confinement of plasmonic waveguides remains largely unexplored. Here we report fabrication and study of hybrid graphene-plasmonic waveguide modulators. We consider several types of modulators and identify the most promising one for telecom applications. The modulator working at the telecom range is demonstrated, showing a modulation depth of >0.03 dB µm(-1) at low gating voltages for an active device area of just 10 µm(2), characteristics which are already comparable to those of silicon-based waveguide modulators while retaining the benefit of further device miniaturization. Our proof-of-concept results pave the way towards on-chip realization of efficient graphene-based active plasmonic waveguide devices for optical communications.

Structured assessment for prospective identification of safety signals in electronic medical records: evaluation in the health improvement network.

BACKGROUND: Pharmacovigilance signal detection largely relies on individual case reports, but longitudinal health data are being explored as complementary information sources. Research to date has focused on the ability of epidemiological methods to distinguish established adverse drug reactions (ADRs) from unrelated adverse events. OBJECTIVE: The aim of this study was to evaluate a process for structured clinical and epidemiological assessment of temporally associated drugs and medical events in electronic medical records. METHODS: Pairs of drugs and medical events were selected for review on the basis of their temporal association according to a calibrated self-controlled cohort analysis in The Health Improvement Network. Six assessors trained in pharmacovigilance and/or epidemiology evaluated seven drugs each, with up to 20 medical events per drug. A pre-specified questionnaire considered aspects related to the nature of the temporal pattern, demographic features of the cohort, concomitant medicines, earlier signs and symptoms, and possible confounding by underlying disease. This informed a classification of drug-event pairs as known ADRs, meriting further evaluation, or dismissed. RESULTS: The number of temporally associated medical events per drug ranged from 11 to 307 (median 50) for the 42 selected drugs. Out of the 509 relevant drug-event combinations subjected to the assessment, 127 (25 %) were classified as known ADRs. Ninety-one (24 %) of the remaining pairs were classified as potential signals meriting further evaluation and 291 (76 %) were dismissed. Suggestive temporal patterns and lack of clear alternative explanations were the most common reasons that drug-event pairs were classified as meriting further evaluation. Earlier signs and symptoms and confounding by the underlying disease were the most common reasons that drug-event pairs were dismissed. CONCLUSIONS: Exploratory analysis of electronic medical records can detect important potential safety signals. However, effective signal detection requires that statistical signal detection be combined with clinical and epidemiological review to achieve an acceptable false positive rate.

Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension.

Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The aim of the current study was to examine the impact of prenatal GC exposure on the postnatal regulation of the gene encoding for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the biosynthesis of the catecholamine, epinephrine. PNMT has been linked to hypertension and is elevated in animal models of hypertension. Male offspring of Wistar-Kyoto dams treated with dexamethasone (DEX) developed elevated systolic, diastolic and mean arterial blood pressure compared to saline-treated controls. Plasma epinephrine levels were also elevated in adult rats exposed to DEX in utero. RT-PCR analysis revealed adrenal PNMT mRNA was higher in DEX exposed adult rats. This was associated with increased mRNA levels of transcriptional regulators of the PNMT gene: Egr-1, AP-2, and GR. Western blot analyses showed increased expression of PNMT protein, along with increased Egr-1 and GR in adult rats exposed to DEX in utero. Furthermore, gel mobility shift assays showed increased binding of Egr-1 and GR to DNA. These results suggest that increased PNMT gene expression via altered transcriptional activity is a possible mechanism by which prenatal exposure to elevated levels of GCs may program for hypertension later in life.

Do chart reviews and interviews provide the same information about breast and cervical cancer screening?

The National Cancer Institute of the United States has set a goal for the year 2000 that 80-90% of eligible women should have a Pap smear every 3 years and that 80% of women aged 50-70 should receive an annual breast examination and mammogram. Very few studies have examined how we might best measure our progress towards this goal. Specifically, should we employ interview data or data derived from medical records? To respond to this question, data were gathered at two different public health clinics in poor areas of Chicago using both techniques. The interviews estimated significantly higher proportions of women receiving Pap smears, breast examinations, and mammograms in the previous 12-month interval than were estimated from randomly selected medical records. A review of the literature suggests the same pattern exists when other studies using these two data gathering processes are compared. We are thus left with a serious problem, one that must be resolved before we will be able to fully assess our progress in increasing breast and cervical cancer screening.

Development of a reverse transcription polymerase chain reaction procedure for the detection of marine caliciviruses with potential application for nucleotide sequencing.

A reverse transcription polymerase chain reaction (RT-PCR) procedure is described for the detection of marine caliciviruses including vesicular exanthema of swine virus (VESV), San Miguel sea lion virus (SMSV), bovine Tillamook virus (BCV Bos-1) and caliciviruses (CV) isolated from dolphin (Cetacean CV), gorilla (Primate CV) and rattlesnake (Reptile CV) using primers (1F and 1R) designed from the capsid-coding region of the viral genome. These primers were compared with those described by Neill, J.D. and Seal, B.S., 1995: Development of PCR primers for specific amplification of two distinct regions of the genomes of San Miguel sea lion and vesicular exanthema of swine viruses, Mol. Cell. Probes 9, 33-38 (Hel1/Hel2), which had been designed from the 2C-like region of the calicivirus genome. Both sets proved to be extremely useful diagnostic tools for all of the known marine calicivirus serotypes with the exception of three: SMSV-8 and -12 and mink CV suggesting that these three caliciviruses may belong to a different group. Neither of the two primer sets reacted with strains of the vesicular disease viruses of foot-and-mouth disease (FMD), swine vesicular disease (SVD) or vesicular stomatitis (VS) nor with two feline caliciviruses (FCV). The 1F/1R primer set has the advantage over the Hel1/Hel2 set in that it generates a larger PCR product for nucleotide sequence investigations and so provides greater opportunity for identifying molecular differences between the viruses.

Evaluating Chicago's success in reaching the Healthy People 2000 goal of reducing health disparities.

OBJECTIVE: This study was designed to assess Chicago's progress from 1980 to 1998 in addressing the Healthy People 2000 goal of reducing health disparities. METHODS: Chicago vital statistics and surveillance data were used to calculate black:white rate ratios of mortality and morbidity for 1980-1998. Mortality and morbidity rate ratios were also used to compare people living in areas with the lowest median household income with those living in the highest for 1979-1981, 1991-1993, and 1996-1998. The health measures included mortality associated with leading causes of death; all-cause mortality, incidence rates for two communicable diseases; and two birth outcomes. RESULTS: Both black:white and low-income:high-income rate ratios monotonically increased for virtually all measures of mortality and morbidity. Almost all of the rate ratios and linear trends were statistically significant. From 1980 to 1998, the black:white rate ratio for all-cause mortality increased by 57% to 2.03. From 1979-1981 to 1996-1998, the low-income:high-income rate ratio for all-cause mortality increased by 56% to 2.68. CONCLUSIONS: These findings provide clear evidence that disparities in health did not decrease in Chicago. Instead, racial and economic disparities increased for almost all measures of mortality and morbidity used in this study. The fact that the Healthy People 2000 campaign to reduce and then eliminate health disparities was not effective must serve as a stimulus for improved strategies.

A nurse-delivered intervention to reduce barriers to breast and cervical cancer screening in Chicago inner city clinics.

An 18-month intervention was implemented to increase breast and cervical cancer screening among poor African-American women in Chicago. Breast and cervical cancer screening programs were set up in two public clinics, one community-based and the other hospital-based. Nurse clinicians and public health workers were used in these programs to recruit women in the clinics and in targeted community institutions to receive free breast and cervical cancer screening. The following barriers were specifically addressed by the intervention: accessibility of screening, knowledge about breast and cervical cancers, access to followup screening examinations, and access to treatment. A computerized followup system was specifically designed to track patients. During the 18 months of the intervention, 10,829 visits were made by 7,654 low-income women. A total of 84 cases of breast cancer and 9 cases of cervical cancer were detected. Awareness of the program, as measured by a survey after the completion of the intervention, increased in both clinics compared with baseline results. Knowledge about breast and cervical cancers also increased, as measured by scores on tests given before and after a class on breast and cervical cancers. Followup rates were 86 percent for women attending the programs. More than 90 percent of the women referred for evaluation of breast abnormalities kept an appointment. In summary, the intervention was successful in reducing barriers to breast and cervical cancer detection and in attracting a high-risk group of women.

An urban community-based cancer prevention screening and health education intervention in Chicago.

Most types of cancer are disproportionately present in black populations. Among all ethnic and racial groups, black people have the highest incidence of all types of cancer combined, experiencing the highest mortality and the worst survival rate. A major intervention effort has begun in Chicago, targeting women living in 10 south side community areas whose populations are almost all black and among the poorest in the city. The purposes of the intervention are to develop and evaluate ways to reduce morbidity and mortality from breast and cervical cancer. Three outcome measures are being used, the proportion of women who receive Papanicolaou smears, breast examinations, and mammograms; the scores derived from a knowledge, attitudes, and practices survey; and the stage of diagnosed cancer. The results are being evaluated in three locations, the 10 target community areas, a Chicago Health Department clinic located in the community, and Fantus Clinic at Cook County Hospital. The intervention consists of reducing barriers to care at both public clinic sites and delivering education and information within the community. Public health outreach workers who are culturally sensitive to the population bring word of the program to places frequented by women, including local businesses (such as beauty shops, grocery stores, pharmacies, and currency exchanges), public housing developments (one being the largest in the country), and facilities belonging to city services programs. The intervention was developed to permit its ready adoption in similar environments should the evaluation results prove its usefulness.

Field and laboratory analysis of an outbreak of foot and mouth disease in Bulgaria in 1991.

In July 1991, an outbreak of foot and mouth disease (FMD) occurred near Stefan Karadjovo village in Boliarovo (south-east Bulgaria, close to the Turkish border). The virus isolated was identified in Bulgaria as serotype O and this was subsequently confirmed by the World Reference Laboratory for Foot and Mouth Disease in Pirbright (United Kingdom). Serological studies using bovine sera and monoclonal antibody analysis were made. In addition, the sequence of approximately 170 nucleotides at the 3' end of the 1D gene was determined for the field isolate and for vaccine strains used in Bulgaria. These were compared with other sequences of type O FMD viruses from outbreaks in the Middle East. Serum samples were taken from domestic animals in the region close to the outbreak and examined for anti-FMD virus antibodies to assess the extent (if any) of spread of the virus before or after the outbreak. No evidence of infection was found in these animals. The virus involved in the Bulgarian outbreak was antigenically similar to the O1 vaccine strains but probably did not originate from these strains. The virus was closely related genetically to a group of viruses isolated in the Middle East since 1987, suggesting that it may have been introduced into Bulgaria from an area in the Middle East by unidentified means.

Access to primary care for patients with diabetes at an urban public hospital walk-in clinic.

The purpose of this study was to determine the regular source of primary care, the content of care, and barriers to accessing primary care for 218 medically indigent adults with diabetes mellitus. Patients were surveyed at a public hospital walk-in clinic and were queried regarding demographics, regular source of care, and the content of care they received during the preceding year. Seventy percent of the patients were medically uninsured, and 60 percent had household incomes under $10,001. Forty-three percent reported no regular source of care, and 18 percent named an episodic care site as their regular source. Patients with a regular source of primary care had twice as many annual ambulatory visits as those without primary care. Patients with a regular source of primary care reported more diabetic-related services than those without. This patient population is largely poor and uninsured and has difficulty accessing primary care.

Does ethnicity influence obstetric intervention?

AIMS: To examine whether the high proportion of Polynesian women giving birth at Middlemore Hospital contributes to its low interventional delivery rate. METHODS: A study of a one-year cohort of women delivering at Middlemore Hospital. Delivery suite records were scrutinised to determine ethnicity and mode of delivery. Statistical comparisons were made. RESULTS: In Maori, Pacific Island and European women the caesarean section rates were 6.5%, 9.5% and 11.5% respectively. Maori women have a significantly lower rate of caesarean section than Pacific Island women and both groups have a significantly lower rate than European women. The spontaneous vaginal delivery rates in Maori, Pacific Island and European women were 89.0%, 87.4% and 74.8% respectively. CONCLUSION: The high proportion New Zealand Maori and Pacific Island women contributes to, but does not fully explain, the low interventional delivery rate at Middlemore Hospital.

Geographic patterns of disease.

The preparation and use of a computerised grid for demonstrating the temporal and spatial distribution of outbreaks of infectious hepatitis is described. Methods of social area and cluster analysis are described and it is suggested that use could be made in New Zealand of these methods of analysis, taking social data obtained from the census and linking it with mortality and morbidity data obtained by geographical reference.

Criteria for gestational diabetes: a cautionary tale.

The diagnosis of gestational diabetes was developed to predict neonatal outcome (particularly perinatal mortality, macrosomia and hypoglycaemia) and future maternal diabetes. A variety of criteria for this diagnosis have evolved over time, assessed predominantly among European women. We describe a Pacific Islands woman with multiple risk factors for future diabetes yet a borderline 100 g glucose tolerance test result, who delivered a stillborn macrosomic baby weighing 6.7 kg at 38 weeks' gestation. Six weeks postpartum, diabetes was diagnosed by 75 g oral glucose tolerance test. This case highlights the need for caution when interpreting the glucose tolerance test in pregnancy and suggests that closer fetal monitoring and involvement of the diabetes team may be necessary among women with a borderline glucose tolerance test in the presence of additional risk factors for future diabetes (eg obesity, ethnic group).

Ready or not: assessing youths' preparedness for independent living.

This article discusses the utility of the Ansell-Casey Life Skills Assessment (ACLSA) in assessing life skills necessary for living successfully in the community upon emancipation from out-of-home care. ACLSA, completed by youths and their caregivers, identifies skills that have been mastered and those yet to be learned. Assessment information can be used for goal setting, strength identification, and relationship building, as well as to direct program planning and training in self-sufficiency services.

Graphene-protected copper and silver plasmonics.

Plasmonics has established itself as a branch of physics which promises to revolutionize data processing, improve photovoltaics, and increase sensitivity of bio-detection. A widespread use of plasmonic devices is notably hindered by high losses and the absence of stable and inexpensive metal films suitable for plasmonic applications. To this end, there has been a continuous search for alternative plasmonic materials that are also compatible with complementary metal oxide semiconductor technology. Here we show that copper and silver protected by graphene are viable candidates. Copper films covered with one to a few graphene layers show excellent plasmonic characteristics. They can be used to fabricate plasmonic devices and survive for at least a year, even in wet and corroding conditions. As a proof of concept, we use the graphene-protected copper to demonstrate dielectric loaded plasmonic waveguides and test sensitivity of surface plasmon resonances. Our results are likely to initiate wide use of graphene-protected plasmonics.