Does anxiety influence outcome measurements in ankle replacement patients?

BACKGROUND: Total ankle arthroplasty (TAA) is increasingly used to treat end-stage ankle arthritis to restore ankle functional outcomes and alleviate pain. This treatment outcome may be influenced by pre-morbid patient anxiety. METHODS: Twenty-five Infinity TAA implants were prospectively followed post-operatively with a mean follow-up time of 34.18 months. Demographic, clinical, and functional outcomes were assessed. Analysis was performed on the effect of anxiety, reported by the HADS, on patient-perceived postoperative pain, functioning, and quality of life. RESULTS: Postoperative the PROMs and Range of Motion (ROM) improved significantly. Linear regression analysis and Pearson correlation showed a significant negative effect of anxiety on the postoperative patient-reported outcome measurements (EQ-5D-5L, VAS, and MOxFQ) at the end of follow-up. CONCLUSION: Good functional, clinical, and radiographic results were observed in this prospective cohort study. Anxiety had a negative influence on the outcome of the patient-reported outcome measurements (EQ-5D-5L and MOxFQ) postoperatively. LEVEL OF EVIDENCE: Level III, prospective cohort study.

'This battle, between your gut feeling and your mind. Try to find the right balance': Parental experiences of children with spinal muscular atrophy during COVID-19 pandemic.

AIMS: Parents of children with spinal muscular atrophy (SMA) often struggle with the all-consuming nature of the demands of caring for a child with substantial physical needs. Our aim was to explore experiences, challenges and needs of parents of a child with SMA in a COVID-19 pandemic situation. METHOD: Nineteen parents of 21 children (15 months to 13 years of age) with SMA types 1-3 participated in semi-structured interviews in June to July 2020. The interviews were analysed using inductive thematic analysis. RESULTS: Parents mentioned the protection of the health and well-being of the child as the central perspective and driving force during the COVID-19 pandemic. Three subthemes were identified: (1) responsibility, (2) balancing vulnerability and resilience and (3) (in)security. Some parents focused on the positive aspects during the lockdown, such as continuation of nusinersen treatment and family life. Some parents described helpful and positive cognitions to cope with the situation. In general, parents described a need for information with regard to COVID-19 and their child with SMA and a need for discussing their dilemmas and insecurities with a healthcare professional. INTERPRETATION: Parents put the health and well-being of their children first during the pandemic. From this study, we learned that parents of children with SMA need information and value direct contact with a healthcare professional to share their dilemmas and insecurities. The dialogue can help to empower parents in the conflicts and decisions they have to make during a pandemic.

[Can staging and profiling ensure that the costs of quality care are adequately reimbursed?]. / Vergoedingsaspecten: kunnen stagering en profilering ervoor zorgen dat de juiste zorg ook juist beloond wordt?

BACKGROUND: The current system for financing effective mental health can improve or reduce the quality of care provided. The system of financing includes reimbursing the care-provider, a risk-adjustment system for the health insurer and personal payments by the patient. Care-providers, patients and health insurers are worried that the current system is detrimental to quality care. AIM: To find out whether the financing system can be improved by the introduction of a system which weighs the costs according to the intensity of the care provided and which is based on staging and profiling. METHOD: We performed a critical evaluation of the current financing system and we explored how staging and profiling could help to keep complex care affordable. RESULTS: The current model for financing mental health care does not involve staging and profiling. Reimbursement is based on diagnoses and on the number of minutes of care provided, no differentiation being made between the levels of expertise required. As a result it can become financially unattractive to administer the best possible treatment to patients with the greatest needs. Staging and profiling have the potential to create the best possible relationship between the level of care needed by the patient and the treatment costs incurred, because the factors that led to the previous imbalance have been removed. CONCLUSION: Staging and profiling can be introduced gradually at roughly the same pace as the national system of risk-adjustment is being introduced for health insurers.

Interference in Genetic Crossing over and Chromosome Mapping.

This paper proposes a general model for interference in genetic crossing over. The model assumes serial occurrence of chiasmata, visualized as a renewal process along the paired (or pairing) chromosomes. This process is described as an underlying Poisson process in which the 1st, n + 1th, 2n + 1th, etc., events are to be interpreted as realized chiasmata. Chromatid interference is described in terms of the probabilities that two successive chiasmata involve two, three or four different chromatids. Several characteristics of this model, e.g., the cytological and genetic mapping function and the density of chiasmata along the chromosomes, are discussed. Some aspects of other interference models are briefly discussed.

High resolution of quantitative traits into multiple loci via interval mapping.

A very general method is described for multiple linear regression of a quantitative phenotype on genotype [putative quantitative trait loci (QTLs) and markers] in segregating generations obtained from line crosses. The method exploits two features, (a) the use of additional parental and F1 data, which fixes the joint QTL effects and the environmental error, and (b) the use of markers as cofactors, which reduces the genetic background noise. As a result, a significant increase of QTL detection power is achieved in comparison with conventional QTL mapping. The core of the method is the completion of any missing genotypic (QTL and marker) observations, which is embedded in a general and simple expectation maximization (EM) algorithm to obtain maximum likelihood estimates of the model parameters. The method is described in detail for the analysis of an F2 generation. Because of the generality of the approach, it is easily applicable to other generations, such as backcross progenies and recombinant inbred lines. An example is presented in which multiple QTLs for plant height in tomato are mapped in an F2 progeny, using additional data from the parents and their F1 progeny.

Multiple alleles for tuber shape in diploid potato detected by qualitative and quantitative genetic analysis using RFLPs.

Tuber shape in potato is commonly regarded as displaying continuous variation, yet at the diploid level phenotypes can be discerned visually, having round or long tubers. Inheritance of qualitative tuber shape can be explained by a single locus Ro, round being dominant to long. With restriction fragment length polymorphisms (RFLPs) the Ro locus was mapped on chromosome 10. Tuber shape was also studied as a quantitative trait, using the length/width ratio as trait value. The estimated broad sense heritability was h2 = 0.80. The morphologically mapped Ro locus explained 75% of the genetic variation, indicating the presence of a major quantitative trait locus (QTL) at the Ro locus and minor genetic factors. RFLP alleles linked with Ro alleles were used to divide the progeny into four genotypic classes: RofemaleRomale:Rofemalero:roRomale:roro = 1:1:1:1. The recessive ro allele is identical by descent in both parents. The significantly different effects (P = 0.0157) of the non-identical alleles Rofemale and Romale provided evidence for multiallelism at the Ro locus. Linkage mapping of the Ro locus was compared with QTL mapping. Only those markers which are polymorphic in both parents allow accurate QTL mapping when genetic factors segregate from both parents. This finding applies to QTL mapping in all outbreeders without homozygous inbred strains.

Integration of the classical and molecular linkage maps of tomato chromosome 6.

In the past, a classical map of the tomato genome has been established that is based on linkage data from intraspecific Lycopersicon esculentum crosses. In addition, a high density molecular linkage map has recently been constructed using a L. esculentum x L. pennellii cross. As the respective maps only partially match, they provide limited information about the relative positions of classical and molecular markers. In this paper we describe the construction of an integrated linkage map of tomato chromosome 6 that shows the position of cDNA-, genomic DNA- and RAPD markers relative to 10 classical markers. Integration was achieved by using a L. esculentum line containing an introgressed chromosome 6 from L. pennellii in crosses to a variety of L. esculentum marker lines. In addition, an improved version of the classical linkage map is presented that is based on a combined analysis of new linkage data for 16 morphological markers and literature data. Unlike the classical map currently in use, the revised map reveals clustering of markers into three major groups around the yv, m-2 and c loci, respectively. Although crossing-over rates are clearly different when comparing intraspecific L. esculentum crosses with L. esculentum x L. pennellii crosses, the clusters of morphological markers on the classical map coincide with clusters of genomic- and cDNA-markers on the molecular map constructed by Tanksley and coworkers.

Comparison between predicted and actual dose distribution in interstitial therapy of the oral cavity.

During the period 1985-1986, 10 patients with lesions of the floor of the mouth or of the mobile part of the tongue were treated by interstitial curietherapie with iridium-192. In the patients treated with the looping technique essential differences were found between the predicted source configuration and that actually achieved, resulting in a disagreement between precalculated and actual dose distribution. To avoid this undesirable situation, a simple oral cavity applicator was constructed which guarantees parallelism and equidistance between the implanted needles. It was found that the use of this applicator resulted in an almost complete agreement between forecast and actual dose distribution.

The role of ecophysiological models in QTL analysis: the example of specific leaf area in barley

Crop modelling has so far contributed little to the genetic analysis of a quantitative trait. This study illustrates how a simple model for crop phenological development, which assumes that crop development rate is affected by daily effective temperature, can assist the identification of Quantitative Trait Loci (QTLs), using specific leaf area (SLA) in barley as an example. The SLA was measured in a field experiment six times during the growing season of 94 recombinant inbred lines (RILs) derived from a cross between cultivars Prisma and Apex. Of the six measurements, one was conducted at the same physiological age for all RILs (at flowering), four were undertaken at specific chronological days prior to flowering, and the last one was taken at 14 days after flowering. When the measured SLA was directly used as the quantitative trait, one to three QTLs were detected for SLA at each measurement time. The major dwarfing gene denso segregating in the population was found to affect SLA strongly at all measurement times except at flowering. If SLA of the different RILs was corrected for differences in physiological age at the time of measurement, by the use of the crop development model, QTLs were detected for SLA at only three stages. Furthermore, the effect of the denso gene was no longer significant during the preflowering stages. The effect of the denso gene detected in the first instance was therefore the consequence of its direct effect on the duration of the preflowering period. This demonstrates the important role that crop development models can play in QTL analysis of a trait that varies with developmental stage. Potential uses of ecophysiological crop growth models in QTL analysis are briefly discussed.

Clonal analysis of radiation-induced translocations in stem-cell spermatogonia of normal and T70H translocation heterozygous mice.

7 T(1;13)70H/+ and 13+/+ male mice were given 2 doses of 250 rad acute X-rays separated by 24 h. The +/+ mice were analysed in 2 groups during the first meiotic division for induced translocations, on average 177 and 233 days after irradiation, and the T70H/+ mice were analysed in parallel with the second group of +/+ males. One testis was treated with normal air-drying procedures yielding a random sample of cells. The other testis was processed according to a new technique, which enable separate analysis of the various locations along the seminiferous epithelium where groups of cells are synchronously in the diakinesis-metaphase I stage of meiosis. The number of cells in such groups was estimated. Both capita epididymes were used for a sperm count. In agreement with an earlier finding, fewer induced translocations were recovered from the T70H/+ mice than from +/+ mice (10.6 versus 19.2%, air-drying technique). Estimates of the group sizes in combination with the occurrence of induced translocations yielded the following information. A synchronously moving group of diakinesis-metaphase I cells originates from, on average, 1.25 stem cells (Appendix). We found an indication for a reduction in group size by 33% when a clone originated from a stem cell carrying an induced translocation compared with a wild-type clone (see Appendix). Both, the data on group size and the sperm counts indicate that, 7 months after the irradiation, the seminiferous epithelium has not totally recovered. Final recovery seems to be slower or absent in the T70H/+ males. The data obtained from the T70H/+ heterozygotes indicate the stem-cell spermatogonia to be responsible for the reduction of the rate or translocation induction with this karyotype, either due to a reduced formation rate or due to a diminished capacity of some of the induced translocation-carrying stem cells to proliferate into a clone reaching the meiotic divisions.

Interpretation of UV-survival curves of Aspergillus conidiospores.

Semi-logarithmic dose-response curves for survival of UV-irradiated conidiospores of A. nidulans have an initial shoulder (at low doses) followed by a decline which becomes linear. To explain the initial shoulder and the resulting extrapolation number (log S intercept of the linear extrapolation line) a general model is presented, which includes multi-target (n) and multi-hit (h) effects and allows for the effect of initial repair and of a compound parameter k, which stands for inherent sensitivity of the spores and for dose received inside the spores. From experiments on (a) the modification of k (spore wall colour and shelter effects), (b) a repair-deficient strain (shoulderless) and (c) preincubation during which DNA-replication takes place, it is concluded that the shoulder is generated by initial repair rather than by a multi-hit nature of the cell-killing process. In experiments where k takes different values (sub a and c), notably the position of the point of intersection of the linear lines gives conclusive information. In general, the log S intercept of the linear extrapolation line cannot be used to estimate the target number.

[Home food services for the elderly: the consumer and his appreciation of a warm meal service in Arnhem]. / Maaltijdvoorziening aan huis voor ouderen: de consument en zijn waardering van een warme-maaltijddienst in Arnhem.

An important instrument to achieve prolonged independence of elderly is the provision of meals, in particular cooked meals at home. The purpose of the present study is an evaluation from the consumers perspective of a meals-on-wheels service in Arnhem. Furthermore, the 77 meals-on-wheels consumers in this study, all making intensive use of the service, are described and compared to a representative sample of elderly. The participants appeared to be vulnerable from the perspective of health (particularly the women) and social situation. The perceived quality of both meals and service seem to be high. The taste, the quality of the meat and the first impression of the meal are important determinants of overall perceived meal quality. Responsiveness and reliability have a significant contribution to perceived service quality.

Efficient QTL detection for nonhost resistance in wild lettuce: backcross inbred lines versus F(2) population.

In plants, several population types [F(2), recombinant inbred lines, backcross inbred lines (BILs), etc.] are used for quantitative trait locus (QTL) analyses. However, dissection of the trait of interest and subsequent confirmation by introgression of QTLs for breeding purposes has not been as successful as that predicted from theoretical calculations. More practical knowledge of different QTL mapping approaches is needed. In this recent study, we describe the detection and mapping of quantitative resistances to downy mildew in a set of 29 BILs of cultivated lettuce (L. sativa) containing genome segments introgressed from wild lettuce (L. saligna). Introgression regions that are associated with quantitative resistance are considered to harbor a QTL. Furthermore, we compare this with results from an already existing F(2) population derived from the same parents. We identified six QTLs in our BIL approach compared to only three in the F(2) approach, while there were two QTLs in common. We performed a simulation study based on our actual data to help us interpret them. This revealed that two newly detected QTLs in the BILs had gone unnoticed in the F(2), due to a combination of recessiveness of the trait and skewed segregation, causing a deficit of the wild species alleles. This study clearly illustrates the added value of extended genetic studies on two different population types (BILs and F(2)) to dissect complex genetic traits.

QTL identification for early blight resistance (Alternaria solani) in a Solanum lycopersicum x S. arcanum cross.

Alternaria solani (Ellis and Martin) Sorauer, the causal agent of early blight (EB) disease, infects aerial parts of tomato at both seedling and adult plant stages. Resistant cultivars would facilitate a sustainable EB management. EB resistance is a quantitatively expressed character, a fact that has hampered effective breeding. In order to identify and estimate the effect of genes conditioning resistance to EB, a quantitative trait loci (QTL) mapping study was performed in F2 and F3 populations derived from the cross between the susceptible Solanum lycopersicum (syn. Lycopersicon esculentum) cv. 'Solentos' and the resistant Solanum arcanum (syn. Lycopersicon peruvianum) LA2157 and genotyped with AFLP, microsatellite and SNP markers. Two evaluation criteria of resistance were used: measurements of EB lesion growth on the F2 plants in glasshouse tests and visual ratings of EB severity on foliage of the F3 lines in a field test. A total of six QTL regions were mapped on chromosomes 1, 2, 5-7, and 9 with LOD scores ranging from 3.4 to 17.5. Three EB QTL also confer resistance to stem lesions in the field, which has not been reported before. All QTL displayed significant additive gene action; in some cases a dominance effect was found. Additive x additive epistatic interactions were detected between one pair of QTL. For two QTL, the susceptible parent contributed resistance alleles to both EB and stem lesion resistance. Three of the QTL showed an effect in all tests despite methodological and environmental differences.

Construction of an integrated map of rose with AFLP, SSR, PK, RGA, RFLP, SCAR and morphological markers.

A high-density genetic map with a number of anchor markers has been created to be used as a tool to dissect genetic variation in rose. Linkage maps for the diploid 94/1 population consisting of 88 individuals were constructed using a total of 520 molecular markers including AFLP, SSR, PK, RGA, RFLP, SCAR and morphological markers. Seven linkage groups, putatively corresponding to the seven haploid rose chromosomes, were identified for each parent, spanning 487 cM and 490 cM, respectively. The average length of 70 cM may cover more than 90% of the rose genome. An integrated map was constructed by incorporating the homologous parental linkage groups, resulting in seven linkage groups with a total length of 545 cM. The present linkage map is currently the most advanced map in rose with regard to marker density, genome coverage and with robust markers, giving good perspectives for QTL mapping and marker-assisted breeding in rose. The SSR markers, together with RFLP markers, provide good anchor points for future map alignment studies in rose and related species. Codominantly scored AFLP markers were helpful in the integration of the parental maps.

Marker densities and the mapping of ancestral junctions.

In any partially inbred population, 'junctions' are the loci that form boundaries between segments of ancestral chromosomes. Here we show that the expected number of junctions per Morgan in such a population is linearly related to the inbreeding coefficient of the population, with a maximum in a completely inbred population corresponding to the prediction given by Stam (1980). We further show that high-density marker maps (fully informative markers with average densities of up to 200 per cM) will fail to detect a significant proportion of the junctions present in highly inbred populations. The number of junctions detected is lower than that which would be expected if junctions were distributed randomly along the chromosome, and we show that junctions are not, in fact randomly spaced. This non-random spacing of junctions significantly increases the number of markers that is required to detect 90% of the junctions present on any chromosome: a marker count of at least 12 times the number of junctions present will be needed to detect this proportion.

Linkage disequilibrium causing selection at a neutral locus in pooled Tribolium populations.

The role of linkage disequilibrium with respect to the changes in allele frequencies at a marker locus in newly started polymorphic populations is demonstrated using the marker locus black in Tribolium. The experiments, jointly taken, indicate that the black locus is selectively neutral, or nearly so, under the current experimental conditions. A number of possible mechanisms for selection at the neutral marker locus, i.e. a single linked or non-linked locus and a number of linked and/or non-linked loci through which selection acts, are discussed. On the basis of the experiments some of these models can be excluded, leaving three models for further evaluation: (A) a single linked fitness locus, (B) a number of linked fitness loci and (C) a number of both linked and non-linked fitness loci. The first of these models allows estimation of parameters (recombination fraction and selection coefficients). Models B and C are described in terms of heterozygosity of chromosome pairs. It is argued that in view of the history of a laboratory mutant stock, model C fits best to the experimental results.