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.

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.

Management of thyroid carcinoma with radioactive 131I.

PURPOSE: To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. METHODS AND MATERIALS: Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. RESULTS: With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. CONCLUSIONS: Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10.

A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.

The influence of racial mix on comparisons of perinatal mortality rate between Area Health Authorities.

The proportion of births to women of New Commonwealth origin in different Area Health Authorities (AHAs) varies widely. The influence of this varying proportion in contributing to differences in perinatal mortality rate (PNMR) between authorities is examined. Firstly, it is shown that the two main 'immigrant' groups have adverse PNMRs compared with Europeans, and that there is a positive correlation between the proportion of immigrant births in an Area and the PNMR. Secondly it is shown that immigrants have PNMRs (standardised for birth weight distribution) better than those of Europeans, and that there is a negative correlation between the proportion of immigrant births in an Area and the standardised PNMR of the whole Area. Thirdly, based on data from Birmingham a correction factor is developed and applied to the standardised PNMR to examine the effect of adjusting for racial mix. Factors other than birthweight contributint to variation between races in their PNMRs are discussed. It is concluded that the effect of race in contributing independently of birthweight to variation between Areas in respect of PNMRs is insufficient to invalidate inter-Area comparisons.

Interferences and their elimination in the determination of the noble metals by atomic-absorption spectrophotometry.

A number of serious interferences in the determination of the noble metals by atomic-absorption spectrophotometry have been investigated, and ways of eliminating them considered. The use of the nitrous oxide and acetylene flame reduced many of the interferences but also reduced the sensitivity. Additions of lanthanum, copper sulphate, copper + cadmium sulphate, uranium, and vanadium as releasing agents were effective in the removal of interferences for one or more of the noble metals in the air-acetylene flame. Uranium additions were found to be effective in removing mutual interferences associated with the noble metals (osmium and indium were not tested) whereas vanadium removed mutual and base-metal interferences. The precision and accuracy of methods of analysis based on the use of uranium and vanadium were acceptable, and the application of these methods to the analysis of noble metals collected by various procedures is briefly discussed.

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 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 treatment of congenital idiopathic nystagmus by intermittent photic stimulation.

An analysis is presented of the results obtained by treating 54 patients with congenital nystagmus using intermittent photic stimulation. The major beneficial effect has been to improve the visual acuity, though the nystagmus itself is sometimes reduced in amplitude or even eliminated; an unexpected bonus, in certain cases, is the improvement in stereoscopic acuity.

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.

Measurement of phosphoinositide-specific phospholipase C activity in mononuclear leucocytes from atopic and normal subjects.

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Non-specific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics.

Acquired eruptive haemangiomata with primary biliary cirrhosis and prostatic carcinoma.

We report a male patient with acquired eruptive haemangiomata occurring in association with primary biliary cirrhosis and a carcinoma of the prostate. The possible explanations include an abnormality of sex sterol metabolism associated with his liver disease, secretion of an angiogenic factor by his carcinoma or a combination of the two mechanisms.

Cervical spine dysraphism with teratoma exhibiting pulmonary differentiation: case report and review of the literature.

Spinal dysraphism and teratomas are well-recognized spinal cord lesions, but both entities are rare in the cervical spinal cord. Rarely, teratomas have been described within dysraphic lesions in the thoracic and lumbosacral regions. To date, teratomas contained within cervical spine dysraphic lesions have not been described. Although mature cystic teratomas are renowned for the array of organoid tissue differentiation they display, mature lung differentiation is a rarity. While pulmonary differentiation has been described in six female genital tract teratomas, it has not been reported in spinal teratomas. The clinicopathologic features of a complex cervical lesion, comprising a combination of cervical spine dysraphism with a mature cystic teratoma that exhibited pulmonary differentiation, is presented, and the literature on teratomas exhibiting pulmonary differentiation is reviewed.

Acral persistent papular mucinosis.

The case is reported of a 56-year-old man with an unusual papular eruption on the forearms with deposition of mucin in the dermis. The clinical and histopathological features were consistent with acral persistent papular mucinosis, a recently described focal type of cutaneous mucinosis.