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Background We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. Methods Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2–positive (SARS-CoV-2–positive) cases aged 12–85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2–negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.World Health Organization.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented disruption to society, which indirectly affects infectious disease dynamics. We aimed to assess the effects of COVID-19-related disruption on dengue, a major expanding acute public health threat, in southeast Asia and Latin America.METHODS: We assembled data on monthly dengue incidence from WHO weekly reports, climatic data from ERA5, and population variables from WorldPop for 23 countries between January, 2014 and December, 2019 and fit a Bayesian regression model to explain and predict seasonal and multi-year dengue cycles. We compared model predictions with reported dengue data January to December, 2020, and assessed if deviations from projected incidence since March, 2020 are associated with specific public health and social measures (from the Oxford Coronavirus Government Response Tracer database) or human movement behaviours (as measured by Google mobility reports).FINDINGS: We found a consistent, prolonged decline in dengue incidence across many dengue-endemic regions that began in March, 2020 (2·28 million cases in 2020 vs 4·08 million cases in 2019; a 44·1% decrease). We found a strong association between COVID-19-related disruption (as measured independently by public health and social measures and human movement behaviours) and reduced dengue risk, even after taking into account other drivers of dengue cycles including climatic and host immunity (relative risk 0·01-0·17, pINTERPRETATION: In most countries, COVID-19-related disruption led to historically low dengue incidence in 2020. Continuous monitoring of dengue incidence as COVID-19-related restrictions are relaxed will be important and could give new insights into transmission processes and intervention options.FUNDING: National Key Research and Development Program of China and the Medical Research Council.

Introduction: Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. The purpose of the present study was to define whether the biological or chemical structure of a liposome influences cellular and biological regeneration in the skin and to determine by which mechanisms possible changes occur. Methods: Rats were inflicted a full-excision acute wound and divided into three groups to receive weekly subcutaneous injections of DMRIE liposomes plus the Lac-Z gene, or DOTAP/Chol liposomes plus the Lac Z gene, or saline. Planimetry, immunological assays, histological, and immunohistochemical "techniques were used to determine molecular mechanisms after gene transfer, protein expression, dermal, and epidermal regeneration. Results: DOTAP/Chol increased IGF-I and KGF protein concentration and caused concomitant cellular responses, e.g., by increasing IGFBP-3, p

C-reactive protein (CRP) is a common laboratory infection marker in blood-serum of patients. In all diverse medical departments CRP is often used, and also in orthopaedics CRP is proved to be very helpful in diagnosis and monitor of infections. CRP in most fields is superior to conventional and newer infection parameter and is a basic parameter for inflammation. Especially for detection of an early postoperative infection CRP can be very helpful as an objective parameter easy to obtain. In uneventful operative treatment a similar evolution in CRP concentrations was found: the peak level occurred on the second or third postoperative day and reflected the extent of surgical trauma. A second rise of CRP in the postoperative course indicates a complication. Highest levels are reached in bacterial infection after the forth postoperative day with a cut-off level about 10 mg/dl. CRP can also be used as a preoperative marker for risk stratification and newer times CRP is reported as an independent fracture-risk-factor. In general CRP is the basic inflammatory parameter in orthopaedic surgery and is more significant and common than WBC or ESR. But CRP is only a laboratory parameter and must always be correlated with clinical signs of infection.

The interest in single molecule spectroscopy by means of surface enhanced Raman scattering (SERS) has grown enormously in the last five years. Unfortunately, the basic mechanisms leading to the giant enhancement of the Raman signals are still not understood. Almost every group working in the field of single molecule SERS uses silver or gold colloids prepared by a chemical reduction method, to which a highly diluted solution of the target molecules is added. After that, the colloids, are deposited gravitationally onto a glass cover slide. This leads to clusters of several nanoparticles with a large distribution regarding size and shape as well as the Raman efficiency, and the systematic investigation of sm-SERS suffers from this. Our aim was to develop a method to deposit silver clusters showing a high enhancement factor in a controlled way. For this purpose we used an electrochemical double-pulse method, which allows to control the particle size and density by systematic variation of the pulse parameters. We also compared measurements obtained with these surfaces to measurements made with colloids at the single molecule level.

Localized silver and gold nanoparticles, electrochemically prepared by means of the double-pulse technique, were investigated with respect to their optical and spectroscopic properties by scanning confocal microscopy combined with surface enhanced Raman spectroscopy (SERS) and subsequent comparison with the local image of scanning electron microscopy (SEM). Analogous to the silver cluster preparation technique, controlled electrodeposition of gold nanoparticles was demonstrated, varying size from 10 to 500 nm and particle density. The maximum SERS enhancement factors found in the measurements were: (i) 10 10 for silver particles and (ii) 10 8 for gold particles. The optical and spectroscopic data of the local nanoparticle structures investigated showed that SERS is a local phenomenon, because (i) only few particles are Raman active particles, (ii) strongest enhancements in SERS are obtained from particle agglomerates, (iii) typically the Raman radiation is emitted from irregular structures like the necks between two or more particles agglomerated. In the investigated range from 10 to 500 nm no significant influence of the particle size was observed.

Fractures of the medial clavicle third are rare injuries. Even in case of significant fracture displacement, their therapeutic management has been nonoperative. Recently, surgical intervention has become mandatory for displaced fractures types to prevent non-union and functional complaints, but the optimal operative strategy is being discussed controversially.We describe the case of a 63-year-old male patient with a significantly displaced medial clavicle fracture after failed conservative treatment resulting in restricted, painful shoulder function. The patient underwent open reduction and osteosynthesis with an anatomically precontoured locking compression plate (LCP). One year after surgery the patient is free of complaints and has returned to his preinjury activity level without any functional restrictions.As a not yet reported operative approach, anatomically preshaped locking plating seems to be an effective fixation method for displaced fractures of the medial clavicle third. The operative management is described in detail and discussed with the current literature. Based on the presented case, we underline the statement that displaced medial clavicle fractures should be surgically addressed to avoid late damage.

The influence of pulse parameters of a potentiostatic double-pulse on the size distribution of silver clusters was investigated. The silver clusters were deposited from a cyanide-containing electrolyte onto indium–tin oxide electrodes. Clusters with particle diameters of 100–300 nm can be prepared on a time scale of minutes. A model is presented, which is able to explain the experimental results.

Confocal laser microscopy coupled with fluorescence- and Raman spectroscopy was used to investigate optical properties of single silver nuclei (clusters). A double pulse method was used to prepare cluster distributions of homogeneous size and surface density. The clusters show large spectral differences and a characteristic time dependence of the Raman bands.

The growth of copper layers electrodeposited from acidic solutions is investigated by in situ ellipsometry. The effect of nicotinic acid on the properties of the copper deposits is also reported. Refractive indices and extinction coefficients of films formed under diferent conditions were obtained by the use of optical models. The ellipsometric results can be interpreted using an anisotropic single layer model for the copper coatings which is related to the morphology of the deposits. The optical constants are strongly dependent on the deposition potential. The presence of the additive modifies slightly the optical properties of the electrodeposited copper layers.

Chronic and atraumatic groin pain may be due to a variety of pathologies local to and distal from the hip joint. Aside from frequent entities, such as inguinal hernia, impingement of the iliopsoas muscle by the anterior rim of the acetabular component leading to a hematoma can be a potential cause after total hip replacement (THR).This article presents three cases of delayed groin pain after THR received due to osteoarthrosis of the hip joint several years prior to the onset of symptoms. In all three cases the patient suffered from chronic groin pain aggravated by active flexion without direct trauma. After thorough clinical, laboratory and radiological (ultrasound, x-ray, computed tomography) examination a hematoma of the iliopsoas muscle was detected. Furthermore, in all three cases the acetabular component appeared to be slightly malpositioned. Considering the least invasive procedure all cases were treated with an excavation of the hematoma. After recurrence the indications for revision of the malpositioned acetabular component were present.All patients clearly showed a reduction of pain after operative revision. There have been no further hematomas and the patients could be easily and rapidly remobilized.Persistent atraumatic groin pain connected to a deficit in hip flexion after THR needs thorough investigation by the treating physician. The differential diagnosis of a delayed hematoma due to impingement of the iliopsoas muscle is a rare but more complex entity. After careful consideration of the perioperative risks an early indication for revision of a malpositioned acetabular component is promising.

The optical and spectroscopic properties of nanoparticles are of interest for a wide variety of methodic and technical fields of applications. The investigation of nanoparticles requires convincing characterization methods with high spatial resolution. The surface-enhanced Raman spectroscopy is a sensitive tool for characterizing the chemical structure of metal nanoparticles like gold, silver, or copper. If combined with local confocal microscopy it becomes a method for delivering optical and geometrical information of nanosize metallic structures. This method is called confocal surface-enhanced Raman spectroscopic (SERS) microscopy. The fundamentals and significance of confocal SERS microscopy are described based on literature data and recent results of own studies.

The membrane-bound phytoene dehydrogenase (PD) is an enzyme in carotenoid biosynthesis which is essential in all microorganisms and plants containing these colored pigments. Despite its key role in the regulation of carotenogenesis, the biochemistry and molecular biology of PD are poorly understood. We have cloned, sequenced and expressed a portion of the PD-encoding gene, crtI, from the blue-green algae Aphanocapsa PCC6714. The gene codes for a 532-amino acids (aa) protein, with a calculated Mr of 52,598 Da. Two regions of the aa sequence share significant homology with PD from the purple bacterium Rhodobacter capsulatus, including a 30-aa region which has been proposed to be specific for dehydrogenases in carotenoid biosynthesis.

Liposomal gene transfer is an effective therapeutic approach to improve dermal and epidermal regeneration. The purpose of the present study was to define whether the biological or chemical structure of a liposome influences cellular and biological regeneration in the skin, and to determine by which mechanisms possible changes occur. Rats were inflicted a full-excision acute wound and divided into three groups to receive weekly subcutaneous injections of DMRIE liposomes plus the Lac Z gene, or DOTAP/Chol liposomes plus the Lac Z gene, or saline. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine cellular responses after gene transfer, protein expression, dermal and epidermal regeneration. DOTAP/Chol increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example, by increasing IGFBP-3, P

Pathological blood platelet activation promotes thrombosis in cancer patients, but the specific substances involved are still under investigation. Tumor exudates have been described to contain lysophosphatidic acid (LPA), a known platelet-activating substance, and the concentration of mediators present in malignant ascites are constantly equilibrated with the concentration in plasma. We hypothesized that the ascites of cancer patients might activate platelets, and that this may be caused by LPA. Indeed, ascites samples from 15 different patients with cancer induced shape change and an increase of cytosolic Ca2+ of isolated platelets; both responses were cross-desensitized by lysophosphatidic acid (LPA), but not by other platelet stimuli. Moreover shape change, Ca2+ mobilization and aggregation induced by ascites could be completely blocked by pretreatment of platelets with specific LPA-receptor antagonists. Phospholipids were extracted from ascites, separated by thin layer chromatography, and individual fractions were tested for activity on platelets. The platelet activating substance co-migrated with LPA, whereas other fractions were inactive. Notably, ascites induced through LPA-receptor activation platelet aggregation in whole blood. Our results suggest that LPA plays an essential role in the pathological platelet activation in cancer patients. We propose that LPA receptor antagonists could be effective in blocking cancer-associated platelet activation and thus preventing thrombosis.

Carotenoid biosynthesis in the photosynthetic bacterium Rubrivivax gelatinosus leads to the formation of hydroxyspheroidene and spirilloxanthin as the products of a branched pathway. In this study we investigated the role of the desaturase encoded by crtD which catalyses the introduction of C-3,4 double bonds into acyclic carotenoids. The desaturase was expressed in Escherichia coli, and the activity and the substrate specificity of the enzyme were evaluated in vitro by application of structurally different carotenoids. The results indicate that the enzyme is a 3,4-desaturase that converts 1-hydroxy carotenoids. The 3,4-desaturation reaction can only occur with mono-1-hydroxy carotenoids at a psi-end group or with 1,1'-dihydroxy derivatives carrying a 3',4'-double bond. In addition, 1-HO-zeta-carotene could also be converted by the desaturase. Enzyme kinetic studies showed a substrate preference of 1-HO-neurosporene over 1-HO-lycopene. Consequences from the biochemical data for the reaction sequence of hydroxyspheroidene and spirilloxanthin formation and the interconnection of both branches are discussed.

The carotenogenic (crt) gene cluster from Brevibacterium linens, a member of the commercially important group of coryneform bacteria, was cloned and identified. An expression library of B. linens genes was constructed and a fragment of the crt cluster was obtained by functional complementation of a colourless B. flavum mutant, screening transformed cells for production of a yellow pigment. Subsequent screening of a cosmid library resulted in the cloning of the whole crt cluster from B. linens. All genes necessary for the synthesis of the aromatic carotenoid isorenieratene were identified on the basis of sequence homologies. In addition a novel type of lycopene cyclase was identified by complementation of a lycopene-accumulating B. flavum mutant. Two genes, named crt Yc and crt Yd, which code for polypeptides of 125 and 107 amino acids, respectively, are necessary to convert lycopene to beta-carotene. The amino acid sequences of these polypeptides show no similarity to any of the known lycopene cyclases. This is the first example of a carotenoid biosynthetic conversion in which two different gene products are involved, probably forming a heterodimer.

The genomic DNA sequence of Synechocystis was analysed for putative zeta-carotene desaturase genes. Two promising candidates slr0940 and slr0033 were found with similarities to the structurally different zeta-carotene desaturase genes from higher plants and Anabaena, respectively. Only the expression product of the analogue to the plant gene, slr0940, was able to mediate the 2-step desaturation of zeta-carotene via neurosporene to lycopene after complementation of this pathway in Escherichia coli. When enzyme reactions were carried out with this protein, activity was obtained with either zeta-carotene or neuroporene as substrates. The in vitro reaction was inhibited by the pyrimidine derivative J852 which is effective as experimental herbicide in plants. The occurrence of two different types of zeta-carotene desaturases among cyanobacteria and the phylogenetic consequences on chloroplast evolution are discussed.

This paper presents a Monte Carlo maximum likelihood method of estimating Stochastic Volatility (SV). The basic SV model can be expressed as a linear state space model with log chi-square disturbances. Assuming the Gaussianity of these disturbances, application of the Kalman filter leads to consistent but inefficient Quasi- Maximum Likelihood (QML) estimation. Addressing this problem the present paper shows how arbitrarily close approximations to the exact likelihood function can be constructed by means of importance sampling. No modifications of this estimation procedure are required when the basic SV model is extended in a number of directions likely to arise in applied empirical research. This compares favourably with alternative approaches. The finite sample performance of the new estimator is shown to be comparable to the Markov Chain Monte Carlo (MCMC) method.

Full length and truncated cDNA expression constructs of the phytoene synthase (psy) gene from tomato have been ligated into a pUC8 cloning vector. One of the truncated constructs was introduced into Escherichia coli carrying the Erwinia uredovora GGPP synthase gene. This transformant produced 15,15'-cis-phytoene, which was identified on the basis of its UV and IR spectral data, from geranylgeranyl diphosphate. The function of this gene product was further confirmed by in vitro assay using cell-free extract of E. coli harboring the construct. On transformation with the above constructs together with a plasmid containing the carotenoid gene cluster from E. uredovora devoid of the phytoene synthase (crtB) gene, yellow, carotenoid-containing, E. coli colonies were produced. The amounts of carotenoids synthesized by the transformed cells, related to the steady-state levels of psy mRNA, varied depending upon the psy constructs. The full-length psy clone produced 16-fold less carotenoids per unit amount of RNA than cells containing phytoene synthase without the first 114 N-terminal amino acids. Removal of further amino acids from the N-terminus caused a large decrease in carotenogenesis. A Western blot of ripe fruit stroma with a monoclonal antibody raised against phytoene synthase revealed a single protein band of apparent molecular mass 38 kDa. Based upon this immunological evidence, we conclude that the size of the transit peptide of phytoene synthase from ripe tomato fruit is approximately 9 kDa, corresponding to about 80 amino acid residues.(ABSTRACT TRUNCATED AT 250 WORDS)

A plasmid has been constructed by cloning the complete crtI gene encoding phytoene desaturase from Erwinia uredovora behind the lac Z promoter of pUC18 resulting in a reading frame for the full polypeptide with additional 9 amino acids at the N terminus. This plasmid mediated the overexpression of phytoene desaturase in transformed Escherichia coli. The overexpressed enzyme was sequestrated into inclusion bodies requiring urea treatment for solubilization. Purification to homogeneity was subsequently performed on a DEAE-cellulose column and by SDS-polyacrylamide gel electrophoresis. The purification scheme allowed the isolation of 5.3 mg of homogeneous desaturase protein from 100 ml of E. coli cell suspension. On SDS-polyacrylamide gel electrophoresis an apparent molecular mass of 56.2 kDa was determined. An antiserum raised against phytoene desaturase cross-reacted with the expressed protein and was employed to monitor the isolation steps. Upon removal of urea, desaturase activity was restored. The isolated desaturase catalyzed the conversion of 15-cis-phytoene to trans-lycopene as well as to bisdehydrolycopene. FAD was involved in desaturation, whereas NAD and NADP were inhibitory. This is the first time that a membrane-integrated carotenogenic enzyme has been purified and finally obtained in an active state.

The role of carotenoid genes crtB and crtE has been functionally assigned. These genes were cloned from Erwinia into Escherichia coli or Agrobacterium tumefaciens. Their functions were elucidated by assaying early isoprenoid enzymes involved in phytoene formation. In vitro reactions from extracts of E. coli carrying the crtE gene or a complete carotenogenic gene cluster in which crtB was deleted showed an elevated conversion of farnesyl pyrophosphate (FPP) into geranylgeranyl pyrophosphate (GGPP). These results strongly indicate that the crtE gene encodes GGPP synthase. Introduction of the crtB gene into A. tumefaciens led to the conversion of GGPP into phytoene. This activity was absent in similar transformants with the crtE gene. Thus, the crtB gene probably encodes phytoene synthase, which was further supported by demonstration that phytoene accumulated in E. coli harboring both the crtB and crtE genes.

Six genes have been mapped and identified by hybridization or by carotenoid analysis of deletion mutants on a 9 kb chromosomal fragment originating from Erwinia herbicola Eho 10. These genes include crtB, E and I which have been formerly described for Rhodobacter, and three new ones: crtZ encoding lycopene cyclase, crtH for beta-carotene hydroxylase, and crtG for zeaxanthin glycosilase. Their arrangement on the plasmid has been elucidated.

The yellow pigments of Erwinia herbicola Eho 10 and of a transformed Escherichia coli LE392 pPL376 have been identified as carotenoids. HPLC separation, spectra and in some cases mass spectroscopy demonstrated the presence of phytoene (15-cis isomer), beta-carotene (all-trans, 9-cis and 15-cis), beta-cryptoxanthin ( = 3-hydroxy beta-carotene), zeaxanthin (3,3'-dihydroxy beta-carotene) and corresponding carotene glycosides. In addition, lycopene and gamma-carotene accumulated in the presence of the inhibitor 2-(4-chlorophenylthio)-triethylamine.HCl. Carotenoid content in the transformed E. coli was two-fold higher than in E. herbicola. The pattern of the carotenoids was similar in the two organisms. Inactivation of the katF gene in E. coli resulted in an 85% lowering of carotenoid formation, as did the addition of 0.5% glucose to the medium. Suppression of carotenoid formation by inactivation of the katF gene lowered, but did not abolish, the protection offered by carotenoids against inactivation by alpha-terthienyl plus near-ultraviolet light (320-400 nm).

We have used genetic and biochemical techniques to study carotenoid biosynthesis (crt) mutants of Rhodobacter capsulatus, a purple non-sulfur photosynthetic bacterium. All nine identified crt genes are located within the 46-kilobase pair photosynthesis gene cluster, and eight of the crt genes form a subcluster. We have studied the operon structure of the crt gene cluster using transposon Tn5.7 mutants. The Tn5.7 insertion sites in 10 mutants have been mapped to high resolution (25-267 base pairs) by Southern hybridization. Two insertions each map within the coding regions of the crtA, crtC, crtE, and crtF genes, and one insertion lies within the crtI gene. The insertion in crtI is not polar on the downstream crtB gene, suggesting that crtI and crtB may form two separate operons. Another insertion located in the 5' noncoding region between the divergent crtA and crtI genes has no effect on wild-type pigmentation and apparently lies between the promoters for these operons. A Tn5.7 mutation in the 3' region of crtA yields a bacteriochlorophyll-minus phenotype, while a 5' insertion affects only carotenoid biosynthesis. Regulatory signals for transcription of a downstream operon required for bacteriochlorophyll biosynthesis may thus overlap the coding region of crtA. We also present the first evidence for the functions of the crtB, crtE, and crtJ gene products using a new in vitro assay for the incorporation of [14C]isopentenyl pyrophosphate into carotenoid precursors and phytoene in cell-free extracts. Extracts from a crtE mutant accumulate [14C]prephytoene pyrophosphate, while those from crtB and crtJ mutants accumulate [14C]geranylgeranyl pyrophosphate. We therefore propose that CrtE is the phytoene synthetase and that CrtB, and possibly CrtJ, are components of the prephytoene pyrophosphate synthetase.

Rare forms of incompatibility were observed over a period of 20 years in 41 (2%) of 2088 new-borns with haemolytic disease. Antibodies involved were anti-c (n = 27), anti-E (n = 6) and anti-K (n = 4), as well as one case each of anti-E + Fya, -C, -Fya and -Jka. Amniotic fluid was examined during pregnancy in nine cases, three children were given intra-uterine infusions, while in the remainder the haemolytic process was mild or only moderately severe. One infant died of toxoplasmosis, another one of immaturity and respiratory distress syndrome. Kernicterus was always prevented. In haemolytic disease of the newborn caused by anti-c and anti-E, prenatal damage is markedly rarer than with D erythroblastosis, but must be considered during the pregnancy. In anti-K haemolytic disease the severity of the disease is similar to that of D erythroblastosis. All three incompatibilities may lead to kernicterus in the first few days after birth so that exchange transfusions are often necessary. In most of the other incompatibilities the course is similar to that seen with ABO erythroblastosis.