Rise and fall of sea ice production in the Arctic Ocean's ice factories.

The volume, extent and age of Arctic sea ice is in decline, yet winter sea ice production appears to have been increasing, despite Arctic warming being most intense during winter. Previous work suggests that further warming will at some point lead to a decline in ice production, however a consistent explanation of both rise and fall is hitherto missing. Here, we investigate these driving factors through a simple linear model for ice production. We focus on the Kara and Laptev seas-sometimes referred to as Arctic "ice factories" for their outsized role in ice production, and train the model on internal variability across the Community Earth System Model's Large Ensemble (CESM-LE). The linear model is highly skilful at explaining internal variability and can also explain the forced rise-then-fall of ice production, providing insight into the competing drivers of change. We apply our linear model to the same climate variables from observation-based data; the resulting estimate of ice production over recent decades suggests that, just as in CESM-LE, we are currently passing the peak of ice production in the Kara and Laptev seas.

The importance of accurate pathological assessment of lymph node involvement in colorectal cancer.

This review presents an up-to-date analysis of the importance of accurate pathological lymph node staging in colorectal cancer. Lymph node staging is reliant on the technique of the surgeon and the pathologist as well as methods employed in the histopathology laboratory, and is vital for determining appropriate therapy. The significance of micrometastatic nodal disease is evaluated and new techniques for pathological evaluation are discussed. Recommendations for evaluation of lymph node status in colorectal cancer are provided based on current scientific evidence, and standardization of pathological dissection and laboratory handling is advocated.

Pathways to care and ethnicity. 1: Sample characteristics and compulsory admission. Report from the AESOP study.

BACKGROUND: Many studies have found high levels of compulsory admission to psychiatric hospital in the UK among African-Caribbean and Black African patients with a psychotic illness. AIMS: To establish whether African-Caribbean and Black African ethnicity is associated with compulsory admission in an epidemiological sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas were included in the (AESOP) study. For this analysis we included all White British, other White, African-Caribbean and Black African patients from the AESOP sampling frame. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: African-Caribbean patients were significantly more likely to be compulsorily admitted than White British patients, as were Black African patients. African-Caribbean men were the most likely to be compulsorily admitted. CONCLUSIONS: These findings suggest that factors are operating at or prior to first presentation to increase the risk of compulsory admission among African-Caribbean and Black African patients.

Pathways to care and ethnicity. 2: Source of referral and help-seeking. Report from the AESOP study.

BACKGROUND: Previous research has found that African-Caribbean and Black African patients are likely to come into contact with mental health services via more negative routes, when compared with White patients. We sought to investigate pathways to mental health care and ethnicity in a sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: We included all White British, other White, African-Caribbean and Black African patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: Compared with White British patients, general practitioner referral was less frequent for both African-Caribbean and Black African patients and referral by a criminal justice agency was more common. With the exception of criminal justice referrals for Black African patients, these findings remained significant after adjusting for potential confounders. CONCLUSIONS: These findings suggest that factors are operating during a first episode of psychosis to increase the risk that the pathway to care for Black patients will involve non-health professionals.

Teledermatology in practice.

Teledermatology has been the focus of much interest in recent years. Potential uses include a simple supporting role for primary care, more accurate triage of dermatology patients or an 'advice only' service reducing the need for dermatology patients to attend outpatient clinics. With the current under-provision of dermatology services in the UK and the waiting list targets set by government, teledermatology systems have been proposed as a possible solution. 'Store and forward' teledermatology systems are easy to set up and it has been shown that accurate diagnoses can be made using digital images attached to an E-mailed history. In an area of geographical isolation a store and forward teledermatology system has been used successfully to reduce patient waiting times. In Peterborough we have been using a store and forward teledermatology system for over 4 years. Our experience has demonstrated that for only a small number of selected patients was it possible to provide an advice-only service, but the majority of patients still need to be seen in the outpatient clinic. Despite the technical simplicity of these systems today there is still little evidence that teledermatology will have a significant impact on patient workload in the average dermatology clinic. It must be recognized that teledermatology is potentially a useful communication tool for selected patients in primary care but is unlikely to solve waiting list problems or replace the need for local dermatology services.

The effect of curing with plasma light on the shrinkage of dental restorative materials.

Commercially available light activated dental composites were used in this study to compare the shrinkage following curing with plasma light (Apollo95E, DMDS) and a convention halogen dental curing light (Prismetics Lite II, Dentsply). Polymerization shrinkage was determined by measuring the strain in one dimension by means of a contacting transducer. The percentage linear shrinkage were: Spectrum H = 1.84 + 0.31, P = 1.49 + 0.35*; Ana aesthetic H = 2.04 + 0.38, P = 1.85 + 0.27; Esthet.x H = 1.66 + 0.28, P = 1.69 + 0.25; Dyract AP H = 2.39 + 0.33, P = 2.18 + 0.35*; Apollo Restore H = 1.88 + 0.36, P = 1.42 + 0.33*; Surefil H = 0.88 + 0.28, P = 0.99 + 0.30 where * = significantly different, t-test at P < 0.05. The results suggested that there was less shrinkage when curing some, but not all, materials using the plasma light, although this could be attributed to a reduced level of polymerization.

Palmar filiform hyperkeratosis (FH) associated with underlying pathology?

We describe two patients with palmar filiform hyperkeratosis, characterized by multiple thin spiny keratotic projections on the palms. The condition has been associated with an underlying malignancy in some cases. One patient has myelofibrosis, an association not previously described. In addition we describe a further patient with filiform hyperkeratoses of both palms and soles with no associated underlying disorder. In view of the relatively high risk of underlying malignancy occurring in patients with filiform hyperkeratosis, these patients should always be investigated fully.

A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts.

Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to-normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin "pretargeting" approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine-containing "clearing agent" and finally 3 hours later by (111)In-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional (111)In-1F5. Tumor-to-normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional (111)In-1F5. Therapy experiments demonstrated that 400 microCi (14.8 MBq) or more of conventional (90)Y-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 microCi (29.6 MBq) (90)Y-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing.

A robust method for the preparation and purification of antibody/streptavidin conjugates.

The many uses of antibody-protein conjugates, especially antibody-streptavidin conjugates, give rise to the need for a reliable conjugation method offering reasonable yields and reproducible quality. We describe a method for preparing antibody-streptavidin conjugates that has consistently produced conjugates of quality and in sufficient quantity to be used in the clinical development and evaluation of the Pretarget delivery system. In this method antibody disulfides are reduced to generate reactive thiols, and maleimides are linked to streptavidin with the heterobifunctional cross-linking agent, SMCC. The two activated proteins are then mixed briefly before the conjugation is terminated with an oxidizing agent that reforms disulfides from unreacted thiols. The preponderance of the conjugate produced is 1:1 and 1:2 Ab:SA conjugate. This fraction is isolated from unconjugated proteins and high molecular weight byproduct by iminobiotin affinity and ion-exchange chromatography. The resulting conjugate is at least 90% 1:1 + 1:2 Ab:SA conjugate, contains no SA or Ab, and is produced reproducibly in 37% yield.

A tetravalent single-chain antibody-streptavidin fusion protein for pretargeted lymphoma therapy.

Single-chain Fv antibody fragments from the CD20-specific murine monoclonal antibody B9E9 were genetically engineered as streptavidin fusions [single-chain Fv-streptavidin (scFvSA) fusion protein] for use in pretargeted radioimmunotherapy. The scFvSA constructs were expressed as soluble, tetrameric species in the periplasm of Escherichia coli. Expression levels were affected by the order of the variable regions and the length and composition of the single-chain Fv linker. The best expressor was obtained with the variable regions in the heavy chain-light chain configuration separated by a 25-mer Gly4Ser linker. This construct produced 250-300 mg of soluble, tetrameric fusion protein per liter of fermentor culture. The fusion protein (Mr 173,600) was purified from crude lysates by iminobiotin affinity chromatography with an overall yield of about 50% and was analyzed for functionality both in vitro and in vivo. Immunoreactivity of the scFvSA fusion protein and its nanomolar affinity to CD20-positive Ramos cells were comparable with the B9E9 monoclonal antibody. The fusion protein had a biotin dissociation rate identical to recombinant streptavidin and bound an average of 3.6 biotins/molecule of a possible 4 biotins/molecule. Labeled fusion protein cleared from the blood of BALB/c mice with a P half-life of about 16 h. In nude mice bearing Ramos xenografts, the fusion protein demonstrated sufficient tumor localization of functional streptavidin to enable efficient, tumor-specific targeting of a subsequently administered radionuclide-chelate/biotin molecule. These results suggest that large quantities of functional scFvSA can be produced for clinical testing as a therapy for non-Hodgkin's lymphoma.

Childhood Lichen scrofulosorum revisited.

Lichen scrofulosorum (LS), an uncommon cutaneous tuberculous reaction, has been described in children and young adults. In the last three decades, there has been a dearth of literature on the entity in children, despite a global increase in tuberculosis. It is usually associated with localized cervical, hilar, or mediastinal lymphadenopathy or with osseous tuberculosis. The occurrence of LS in association with pulmonary tuberculosis is rare and its occurrence with generalized lymphadenopathy is unrecognized. We report LS in two children and highlight its occurrence with pulmonary tuberculosis and generalized lymphadenopathy.

Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity.

A covalent conjugate (NR-LU-10/SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10/SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of (90)Y-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600-800 microCi of (90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm(3)) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity.

Factors in the onset of schizophrenia: a comparison between London and Trinidad samples.

OBJECTIVE: Sociodemographic factors play an important role in the genesis of mental disorders. High rates of unemployment and other social factors have been reported previously among African-Caribbeans with schizophrenia in London. The aim of the present study was to compare these factors in Trinidad with London African-Caribbeans. METHOD: Using internationally defined criteria, patients with first-onset schizophrenia were recruited in both countries, and information on the onset of symptoms, help-seeking, pathways into care, premorbid personality and educational and employment status were collected. These two samples are compared on a number of these factors. A total of 56 cases of first onset of psychosis coming into contact with psychiatric services in Trinidad were studied. Of these, 46 cases were diagnosed as having schizophrenia using the CATEGO program. Over a period of 2 years, 38 African-Caribbean patients with schizophrenia were recruited in London. RESULTS: African-Caribbean patients with schizophrenia in London were more likely to be admitted for perceived threat to others and to have shown loss of interest and serious neglect and to have assaulted others. A lower proportion were admitted via a psychiatrist and a higher proportion by the police. The unemployment rate among the London sample of African-Caribbeans was much higher than that in the general population, whereas this was not the case for the Trinidad patients. CONCLUSION: These findings are discussed in the context of culture and aetiology of schizophrenia, and suggestions with regard to future research are made.

Factors in the onset of schizophrenia: a comparison between London and Trinidad samples

Objective: Sociodemographic factors play an important role in the genesis of mental disorders. High rates of unemployment and other social factors have been reported previously among African-Caribbeans with schizophrenia in London. The aim of the present study was to compare these factors in Trinidad with London African-Caribbeans. METHOD: Using internationally-defined criteria, patients with first-onset schizophrenia were recruited in both countries, and information on the onset of symptoms, help-seeking, pathways into care, premorbid personality and educational and employment status were collected. These two samples are compared on a number of these factors. A total of 56 cases of first-onset of psychosis coming into contact with psychiatric services in Trinidad were studied. Of these, 46 cases were diagnosed as having schizophrenia using the CATEGO program. Over a period of 2 years, 38 African-Caribbean patients with schizophrenia were recruited in London. RESULTS: African-Caribbean patients with schizophrenia in London were more likely to be admitted for perceived threat to others and to have shown loss of interest and serious neglect and to have assaulted others. A lower proportion were admitted via a psychiatrist and a higher proportion by the police. The unemployment rate among the London sample of African-Caribbeans was much higher than in the general population, whereas this was not the case for the Trinidad patients. CONCLUSION: These findings are discussed in the context of culture and aetiology of schizophrenia, and suggestions with regard to future research are made. (AU)

Social factors and first onset schizophrenia among Asians and whites.

Previous studies from the Indian subcontinent had suggested that the onset and outcome of schizophrenia is linked with social factors. We set out to study the inception rates and social factors in whites and Asians who were presenting for the first time ever to various catchment facilities in Ealing catchment area. A total of 62 cases (38 white and 24 Asians) were diagnosed as having schizophrenia. Using well established and previously validated standardised instruments we collected information on various social factors and inception rates of schizophrenia. The inception rates and social factors were largely similar in these two groups. By and large the social factors in the two groups were broadly similar except that Asians were significantly more likely to show increased religious activity compared with their white counterparts. Contrary to previous findings Asians were more likely to have had longer duration of symptoms prior to seeking help. These findings are discussed in relation to Asian support systems and suggestions made for future research.

The first contact of patients with schizophrenia with psychiatric services: social factors and pathways to care in a multi-ethnic population.

BACKGROUND: African-Caribbean patients have less desirable routes of entry into the psychiatric services than other ethnic groups in Britain but this may not apply to the first contact with services. METHODS: Patients' pathways to care, type of admission or referral and sectioning details were recorded for all first contact patients presenting to south London psychiatric services over a 2-year period. We also conducted a retrospective analysis of data from the Camberwell Register, comparing rates of compulsory admission between 'Whites' and 'African-Caribbeans' for first and readmissions, over a 20-year period. RESULTS: Our first contact sample comprised 38 White, 38 African-Caribbean and 24 Asian patients with CATEGO defined broad schizophrenia. GP referral was found to be the most common mode of contact and there were no significant differences between the ethnic groups with regard to compulsory admission. Similarly, data from the Camberwell Register showed no significant difference in rates of compulsory admission between first admission White and African-Caribbean patients. However, when all readmissions were examined, African-Caribbeans were more likely to be admitted involuntarily. CONCLUSIONS: Our findings suggest that reports of less desirable routes of entry for African-Caribbean patients into the psychiatric service do not apply to their first admission but are likely to develop over time and repeated contact with the services.

First-contact incidence rate of schizophrenia on Barbados.

BACKGROUND: The incidence rate for broad schizophrenia among second-generation African-Caribbean people in the United Kingdom has been reported as high. Ethnicity, migration and psychosocial stressors have been suggested as causal factors. AIMS: To determine the incidence of schizophrenia for the whole population of Barbados using an identical methodology to two previous studies in Trinidad (Bhugra et al, 1996) and London (Bhugra et al, 1997). METHOD: A 12-month study of all persons in the 18-54-year age group presenting with a psychosis for the first time was carried out on the population of Barbados. Information was collected using World Health Organization screening and measurement instruments. RESULTS: On an island of just over a quarter of a million, 40 out of the 53 patients that met the inclusion criteria were categorised as S+ (narrow) schizophrenia, giving an incidence rate of 2.8/10,000 (95% CI 1.97-3.7). The incidence rate for broad schizophrenia was calculated at 3.2/10,000 (95% CI 2.3-4.1), which is significantly lower than the comparable rate for London's African-Caribbeans of 6.6/10,000 (95% CI 4.5-8.7). CONCLUSIONS: The very high rate for broad schizophrenia among African-Caribbean people in the UK is probably due to environmental factors.

Early manifestations, personality traits and pathways into care for Asian and white first-onset cases of schizophrenia.

BACKGROUND: Previous studies have shown that manifestations of symptoms and premorbid personality of patients with schizophrenia differ across cultures. However, these have only been demonstrated in cultural settings apart from each other. METHOD: We set out to compare these across different ethnic groups from a catchment area in west London. The Asian and the white group had similar inception rates of schizophrenia and we therefore decided to compare these two groups to ascertain similarities in social, demographic and personality factors and pathways into care. First-onset cases of schizophrenia were studied on a number of parameters using previously validated instruments. RESULTS: There were more similarities than differences between the two groups. When compared with the findings of a previous multicentre study in India, London Asians, like their counterparts in India, were more likely than the London white sample to present with loss of appetite, become more religious and behave as if hearing voices. However, compared to their Indian counterparts, the onset of symptoms was more likely to be insidious and alternative sources of healing were less likely to be approached. CONCLUSIONS: These findings are discussed in relation to the findings for white patients and recommendations made for future research.