Estimates of Crop Yield Anomalies for 2022 in Ukraine Based on Copernicus Sentinel-1, Sentinel-3 Satellite Data, and ERA-5 Agrometeorological Indicators.

The study explores the feasibility of adapting the EOStat crop monitoring system, originally designed for monitoring crop growth conditions in Poland, to fulfill the requirements of a similar system in Ukraine. The system utilizes satellite data and agrometeorological information provided by the Copernicus program, which offers these resources free of charge. To predict crop yields, the system uses several factors, such as vegetation condition indices obtained from Sentinel-3 Ocean and Land Color Instrument (OLCI) optical and Sea and Land Surface Temperature Radiometer (SLSTR). It also incorporates climate information, including air temperature, total precipitation, surface radiation, and soil moisture. To identify the best predictors for each administrative unit, the study utilizes a recursive feature elimination method and employs the Extreme Gradient Boosting regressor, a machine learning algorithm, to forecast crop yields. The analysis indicates a noticeable decrease in crop losses in 2022 in certain regions of Ukraine, compared to the previous year (2021) and the 5-year average (2017-2021), specifically for winter crops and maize. Considering the reduction in yield, it is estimated that the decline in production of winter crops in 2022 was up to 20%, while for maize, it was up to 50% compared to the decline in production.

Case report: lipoprotein apheresis reduces the risk of cardiovascular events and prolongs pregnancy in a woman with severely elevated lipoprotein(a), cardiovascular disease, and a high risk of preeclampsia.

Background: Preeclampsia is a common and serious pregnancy-induced disease, with potential severe maternal and fetal complications. Recently, an increased lipoprotein (a) (Lp[a]) concentration, an important factor in cardiovascular diseases (CVDs) pathogenesis, has been identified as a sensitive and specific marker of preeclampsia severity. Although lipoprotein apheresis (LA) is currently used in patients with hyperlipoproteinemia(a) and CVD, real-life data on its efficacy among pregnant women with an increased risk of preeclampsia are limited. Case presentation: We present the case of a pregnant woman with severely elevated Lp(a), two previous episodes of the acute coronary syndrome and multivessel coronary disease treated with long-term LA before pregnancy, and a high risk of preeclampsia (as assessed using combined test screening). An increased pulsatility index and early diastolic notch were observed on Doppler interrogation at 18 weeks' gestation. Biweekly LA therapy was re-initiated at 21 weeks' gestation. The LA safely removed 70% of the serum Lp(a) concentration and reduced low-density lipoprotein-cholesterol (LDL-C) levels by 60%. We also observed an improvement in her urine protein/creatinine ratio, a reduction in the pulsatility index, and a notch on Doppler interrogation. The pregnancy lasted until week 36, when severe preeclampsia prompted an emergency cesarean delivery. Conclusion: Pregnancy in women with elevated Lp(a), CVD, and a high risk of preeclampsia can present challenges in clinical management. Our case report indicates the benefits of LA in preventing atherosclerotic CVD progression during pregnancy, its potential influence on uteroplacental circulation, and prolongation of pregnancy for the best possible intrauterine fetus development. LA may be considered as a treatment option during pregnancy in such conditions. In addition, in pregnant women with CVD, we suggest screening using a combined test and measurement of Lp(a) as a marker of preeclampsia severity.

Cellular Automaton Mimicking Colliding Bodies for Topology Optimization.

Needs and demands of contemporary engineering stimulate continuous and intensive development of design methods. Topology optimization is a modern approach which has been successfully implemented in a daily engineering design practice. Decades of progress resulted in numerous applications of topology optimization to many research and engineering fields. Since the design process starts already at the conceptual stage, innovative, efficient, and versatile topology algorithms play a crucial role. In the present study, the concept of the original heuristic topology generator is proposed. The main idea that stands behind this proposal is to take advantage of the colliding bodies phenomenon and to use the governing laws to derive original Cellular Automata rules which can efficiently perform the process of optimal topologies generation. The derived algorithm has been successfully combined with ANSYS, a commercial finite element software package, to illustrate its versatility and to make a step toward engineering applications. Based on the results of the tests performed, it can be concluded that the proposed concept of the automaton mimicking colliding bodies may be an alternative algorithm to other existing topology generators oriented toward engineering applications.

Changes in global DNA methylation under climatic stress in two related grasses suggest a possible role of epigenetics in the ecological success of polyploids.

Polyploidization drives the evolution of grasses and can result in epigenetic changes, which may have a role in the creation of new evolutionary lineages and ecological speciation. As such changes may be inherited, they can also influence adaptation to the environment. Populations from different regions and climates may also differ epigenetically; however, this phenomenon is poorly understood. The present study analyzes the effect of climatic stress on global DNA methylation based on a garden collection of two related mountain grasses (the narrow endemic diploid Festuca tatrae and the more widely distributed mixed-ploidy F. amethystina) with different geographic ranges and ecological niches. A lower level of DNA methylation was observed for F. tatrae, while a higher mean level was obtained for the diploid and tetraploid of F. amethystina; with the tetraploids having a higher level of global methylated DNA than the diploids. The weather conditions (especially insolation) measured 24 h prior to sampling appeared to have a closer relationship with global DNA methylation level than those observed seven days before sampling. Our findings suggest that the level of methylation during stress conditions (drought, high temperature and high insolation) may be significantly influenced by the ploidy level and bioclimatic provenance of specimens; however an important role may also be played by the intensity of stress conditions in a given year.

Carbohydrate Metabolism Disorders in Relation to Cardiac Allograft Vasculopathy (CAV) Intensification in Heart Transplant Patients According to the Grading Scheme Developed by the International Society for Heart and Lung Transplantation (ISHLT).

BACKGROUND Cardiac allograft vasculopathy (CAV) is the leading complication limiting the long-term survival of heart transplant (HTx) patients. The goal of this study was to assess carbohydrate metabolism disorders in relation to CAV intensification in heart transplant patients according to the ISHLT grading scheme. MATERIAL AND METHODS This retrospective study involved 477 HTx recipients undergoing angiographic observation for up to 20 years after transplantation. The patients were assigned to 4 groups on the basis of their carbohydrate metabolism status: without diabetes, with type 2 diabetes prior to HTx, with new-onset diabetes after transplantation, and with transient hyperglycemia. RESULTS In the study, 62.7% (n=299) of the patients manifested no diabetes after HTx, while 14.3% (n=68) of patients had type II diabetes prior to HTx and 18.4% (n=88) developed new-onset diabetes after transplantation. In total, 1442 coronary angiograms were taken in the specified control periods. CAV incidence increased over time after transplantation, reaching 11% after 1 year, 57% after 10 years, and 50% after 20 years. The longest survival time was observed for patients who had developed type II diabetes prior to HTx, but the difference was not statistically significant. The multivariate analysis failed to identify an independent risk factor for developing cardiac allograft vasculopathy. CONCLUSIONS Despite the relatively high rates of CAV and carbohydrate metabolism disorders in heart transplant patients, our retrospective analysis revealed no statistically significant link between these 2 diseases.

'Defending the unborn', 'protecting women' and 'preserving culture and nation': anti-abortion discourse in the Polish right-wing press.

Poland has one of the strictest abortion laws in Europe, and anti-abortion discourse shapes the debate and social attitudes towards the issue. The paper aims to reconstruct the way in which this discourse, as exemplified in the Polish right-wing press, constructs negative views about abortion and to identify the legitimation mechanisms it employs to sustain its interpretations. Based on our findings, resulting from a content analysis of articles from two right-wing weekly magazines, we distinguish three interrelated frames organising Polish anti-abortion discourse, centred on 'defending the unborn', 'protecting women', and 'preserving culture and nation'. While the first two have occurred in the liberal contexts of Anglophone countries, with one replacing the other, in Polish anti-abortion discourse they co-exist. The construction of abortion as a threat to culture and nation is specific to Poland. We argue that by blending together community-related and individualistic arguments, Polish anti-abortion discourse adapts to wider societal changes observable in the country, thereby sustaining its power to define debate.

Tetraploids expanded beyond the mountain niche of their diploid ancestors in the mixed-ploidy grass Festuca amethystina L.

One promising area in understanding the responses of plants to ongoing global climate change is the adaptative effect of polyploidy. This work examines whether there is a coupling between the distribution of cytotypes and their biogeographical niche, and how different niches will affect their potential range. The study uses a range of techniques including flow cytometry, gradient and niche analysis, as well as distribution modelling. In addition, climatic, edaphic and habitat data was used to analyse environmental patterns and potential ranges of cytotypes in the first wide-range study of Festuca amethystina-a mixed-ploidy mountain grass. The populations were found to be ploidy homogeneous and demonstrate a parapatric pattern of cytotype distribution. Potential contact zones have been identified. The tetraploids have a geographically broader distribution than diploids; they also tend to occur at lower altitudes and grow in more diverse climates, geological units and habitats. Moreover, tetraploids have a more extensive potential range, being six-fold larger than diploids. Montane pine forests were found to be a focal environment suitable for both cytotypes, which has a central place in the environmental space of the whole species. Our findings present polyploidy as a visible driver of geographical, ecological and adaptive variation within the species.

Short-term cell death in tissues of Pulsatilla vernalis seeds from natural and ex situ conserved populations.

Pulsatilla vernalis is a IUCN listed species that occurs in mountain and lowland habitats. The seeds collected from different populations are remarkably diverse in their viability depending on locality or year of collection. We aim to analyse seed viability, among others, by investigation of the percentage of alive, dying, and dead cells in embryos and endosperm when comparing the seeds from a wild lowland population and ex situ cultivation of plants of lowland and Alpine origin. The cell death was detected by staining with two fluorescence probes, one penetrating only the changed nuclear membranes, the other penetrating also the unchanged cells. 54.5% of Alpine origin seeds were presumably capable of germination if they were sown after collection, however, four months later only 36.4% had healthy embryos. In the case of lowland wild plants it was 31.8% and 18.2%, and from ex situ, 27.3% and 13.6%, respectively. 27.3% of Alpine origin seeds had embryo in torpedo stage (9.1% in the case of lowland seeds). Mean weight of the former was 2.9 mg (2.0 mg in lowland ones). Our results confirm the significance of seed origin and seed weight on viability, and that Pulsatilla seeds have a short 'germination time window'.

Sensor-based outdoor monitoring of insects in arable crops for their precise control.

The implementation of precision farming technologies into agricultural practice requires, among other things, precise determination of the extent and intensity of insect infestation in the farmer' fields. Manual insect identification is time-consuming and has low efficiency, especially for large fields. Therefore, scientists and practitioners devote much effort to the automatization of this process. There are two complementary approaches to insect identification: (i) direct, in which the insect (ultimately the species) is determined, and (ii) indirect, in which the damage caused by the insects is monitored and forms the basis on which to formulate the information about insect infestation. A mini-review of both approaches is presented in this work. Additionally, the advantages and disadvantages of each are briefly described. Methods of insect identification are still characterized by relatively small selectivity and efficiency, therefore it is necessary to keep searching for new methods and improve the development of existing ones. The goal of such systems should be to work in real time and be inexpensive to run, enabling widespread use amongst farmers. A possible solution seems to be integrating various techniques (sensor fusion) into a single measurement system. © 2020 Society of Chemical Industry.

Prevalence and Risk Factors of New-Onset Diabetes After Transplantation (NODAT).

BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients. The identification of high-risk patients and the implementation of measures to limit the development of NODAT can improve the long-term patient prognosis. MATERIAL AND METHODS Our study group consisted of 336 patients undergoing heart transplant. Patients with prior diabetes (60 patients) were excluded from analysis. The remaining 276 patients were divided in 2 groups: with NODAT (n=109) and without NODAT (n=167). Logistic regression analysis was used for NODAT risk factor assessment. RESULTS NODAT occurred in 109 (32%) out of 336 patients without diagnosed diabetes before heart transplantation. Risk factors for post-transplant diabetes mellitus, which was shown by the analysis of the collected data, were BMI at discharge (OR=1.082, CI 1.011-1.158, p=0.0233), history of diagnosed CMV infection (OR=1.464, CI 1.068-2.007, p=0.0179), and age over 51 years (OR=1.634, CI 1.274-2.095, p=0.0001). CONCLUSIONS 1. New-onset diabetes after transplantation (NODAT) or long-lasting hypoglycemia (over 2 years after transplantation) was diagnosed in 32% patients after heart transplantation developed. 2. The risk factors of NODAT were BMI at discharge and history of diagnosed CMV infection, and age over 51 years was an independent risk factor.

Direct Analysis of Psilocin and Muscimol in Urine Samples Using Single Drop Microextraction Technique In-Line with Capillary Electrophoresis.

The fully automated system of single drop microextraction coupled with capillary electrophoresis (SDME-CE) was developed for in-line preconcentration and determination of muscimol (MUS) and psilocin (PSC) from urine samples. Those two analytes are characteristic active metabolites of Amanita and Psilocybe mushrooms, evoking visual and auditory hallucinations. Study analytes were selectively extracted from the donor phase (urine samples, pH 4) into the organic phase (a drop of octanol layer), and re-extracted to the acidic acceptor (background electrolyte, BGE), consisting of 25 mM phosphate buffer (pH 3). The optimized conditions for the extraction procedure of a 200 µL urine sample allowed us to obtain more than a 170-fold enrichment effect. The calibration curves were linear in the range of 0.05-50 mg L-1, with the correlation coefficients from 0.9911 to 0.9992. The limit of detections was determined by spiking blank urine samples with appropriate standards, i.e., 0.004 mg L-1 for PSC and 0.016 mg L-1 for MUS, respectively. The limits of quantification varied from 0.014 mg L-1 for PSC and 0.045 mg L-1 for MUS. The developed method practically eliminated the sample clean-up step, which was limited only to simple dilution (1:1, v/v) and pH adjustment.

A stereological study of developmental changes in hepatocyte ultrastructure of zebrafish (Danio rerio).

Histopathology can reveal toxicant-induced changes in the structure of a tissue or organ. A prerequisite for histopathological studies is a sound knowledge of the morphology of the anatomical structure in the normal or healthy state. Zebrafish larvae can provide a tool for studies focused on hepatotoxicity at early stages of development; therefore, the fine structure of the organ should be well characterised. To date, liver structure at 72 and 120 hr post-fertilisation (hpf) has not been reported in detail and this study aimed to fill this scientific gap. A stereological approach allowed for quantitative description of the liver and revealed ultrastructural alterations occurring with time of development. These included a significant increase in the absolute volume of hepatocytes, mitochondria and rough endoplasmic reticulum (rER) during the period of study. The surface area of rER, and of outer and inner mitochondrial membranes also increased. There was no change in the absolute volume of the nuclei. This study provides a quantitative spatial and temporal framework for future research aiming to detect early developmental changes in the liver.

GHOST-Gate to Hybrid Optimization of Structural Topologies.

Although well-recognized in the fields of structural and material design and widely present in engineering literature, topology optimization still arouses a high interest within research communities. Moreover, it is observed that the development of innovative, efficient and versatile methods is one of the most important issues stimulating progress within the topology optimization area. Following this activity, in the present study, a concept of a hybrid algorithm developed in order to generate optimal structural topologies of minimal compliance is presented. The hybrid algorithm is built based on two existing approaches. The first one makes use of the formal optimality criterion, whereas the second one utilizes a special heuristic rule of design variables updating. The main idea that stands behind the concept of the present proposal is to take the advantage of both algorithms capabilities. In a numerical implementation of the hybrid algorithm, the design variables are updated at each iteration step using both approaches, and the solution with a lower objective function value is selected for the next iteration. The numerical tests of the generation of minimal compliance structures have been performed for chosen structures including a real engineering one. It has been confirmed that the proposed hybrid technique based on switching between the considered rules allows the final structures having lower values of compliance as compared with the results of an application of basic algorithms running separately to be obtained. Moreover, based on promising results of the tests performed, one can consider the proposed concept of a hybrid algorithm as an alternative for other existing topology generators.

Interactions of NIPAM nanogels with model lipid multi-bilayers: A neutron reflectivity study.

In dermal drug delivery, the influence of the chemical structure of the carriers on their penetration mechanisms is not yet fully understood. This is a key requirement in order to design highly efficient delivery systems. In this study, neutron reflectivity is used to provide insights into the interactions between thermoresponsive N-isopropylacrylamide based nanogels, cross-linked with 10%, 20% and 30% N,N'-methylenebisacrylamide, and skin lipid multi-bilayers models. Ceramide lipid multi-bilayers and ceramide/cholesterol/behenic acid mixed lipid multi-bilayers were used for this work. The results indicated that in both multi-bilayers the lipids were depleted by the nanogels mainly through hydrophobic interactions. The ability of nanogels to associate with skin lipids to form water-dispersible complexes was found to be a function of the percentage cross-linker. An enhanced depletion of lipids was further observed in the presence of benzyl alcohol, a well-known skin penetration enhancer.

Morphometric traits in the fine-leaved fescues depend on ploidy level: the case of Festuca amethystina L.

BACKGROUND: Polyploid specimens are usually characterized by greater exuberance: they reach larger sizes and/or have a larger number of some organs. Festuca amethystina L. belongs to the section Aulaxyper. Based on morphological features, four subspecies of F. amethystina have been already identified. On the other hand, it has two cytotypes: diploid and tetraploid. The main aim of our study was to distinguish morphological differences between the cytotypes of F. amethystina, assuming that its phenotype differs significantly. METHODS: The nuclear DNA content was measured by flow cytometry in dry leaves from specimens originating from 13 populations of F. amethystina. Several macrometric and micrometric traits of stems, spikelets and leaf blades were taken into account in the comparative analysis of two cytotypes. RESULTS: In the case of cytotypes, specimens of tetraploids were larger than diploids. The conducted morphometric analysis of leaf cross-sections showed significant differences between the cytotypes. DISCUSSION: The research has confirmed for the first time that in the case of F. amethystina the principle of greater exuberance of polyploids is true. Differences between the cytotypes are statistically significant, however, they are not enough to make easy the distinction of cytotypes on the basis of the measurements themselves. Our findings favor the rule known in Festuca taxonomy as a whole, i.e. that the ploidy level can be one of the main classification criteria.

Dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1 form complexes that generate long epimerized 4-O-sulfated blocks.

During the biosynthesis of chondroitin/dermatan sulfate (CS/DS), a variable fraction of glucuronic acid is converted to iduronic acid through the activities of two epimerases, dermatan sulfate epimerases 1 (DS-epi1) and 2 (DS-epi2). Previous in vitro studies indicated that without association with other enzymes, DS-epi1 activity produces structures that have only a few adjacent iduronic acid units. In vivo, concomitant with epimerization, dermatan 4-O-sulfotransferase 1 (D4ST1) sulfates the GalNAc adjacent to iduronic acid. This sulfation facilitates DS-epi1 activity and enables the formation of long blocks of sulfated iduronic acid-containing domains, which can be major components of CS/DS. In this report, we used recombinant enzymes to confirm the concerted action of DS-epi1 and D4ST1. Confocal microscopy revealed that these two enzymes colocalize to the Golgi, and FRET experiments indicated that they physically interact. Furthermore, FRET, immunoprecipitation, and cross-linking experiments also revealed that DS-epi1, DS-epi2, and D4ST1 form homomers and are all part of a hetero-oligomeric complex where D4ST1 directly interacts with DS-epi1, but not with DS-epi2. The cooperation of DS-epi1 with D4ST1 may therefore explain the processive mode of the formation of iduronic acid blocks. In conclusion, the iduronic acid-forming enzymes operate in complexes, similar to other enzymes active in glycosaminoglycan biosynthesis. This knowledge shed light on regulatory mechanisms controlling the biosynthesis of the structurally diverse CS/DS molecule.

Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation.

BACKGROUND: TMEM199 deficiency was recently shown in four patients to cause liver disease with steatosis, elevated serum transaminases, cholesterol and alkaline phosphatase and abnormal protein glycosylation. There is no information on the long-term outcome in this disorder. RESULTS: We here present three novel patients with TMEM199-CDG. All three patients carried the same set of mutations (c.13-14delTT (p.Ser4Serfs*30) and c.92G > C (p.Arg31Pro), despite only two were related (siblings). One mutation (c.92G > C) was described previously whereas the other was deemed pathogenic due to its early frameshift. Western Blot analysis confirmed a reduced level of TMEM199 protein in patient fibroblasts and all patients showed a similar glycosylation defect. The patients presented with a very similar clinical and biochemical phenotype to the initial publication, confirming that TMEM199-CDG is a non-encephalopathic liver disorder. Two of the patients were clinically assessed over two decades without deterioration. CONCLUSION: A rising number of disorders affecting Golgi homeostasis have been published over the last few years. A hallmark finding is deficiency in protein glycosylation, both in N- and O-linked types. Most of these disorders have signs of both liver and brain involvement. However, the present and the four previously reported patients do not show encephalopathy but a chronic, non-progressive (over decades) liver disease with hypertransaminasemia and steatosis. This information is crucial for the patient/families and clinician at diagnosis, as it distinguishes it from other Golgi homeostasis disorders, in having a much more favorable course.

Adsorption versus aggregation of NIPAM nanogels: new insight into their behaviour at the air/water interface as a function of concentration.

We have used neutron reflectivity (NR) measurements in combination with dynamic light scattering (DLS), surface tension and ellipsometry, to study the adsorption behaviour at the air/water interface of N-isopropylacrylamide-based nanogels as a function of concentration. The data provide clear evidence that the nanogels are adsorbed at the interface in a strongly deformed shape and forming a multi-layer where the thickness increases with nanogel concentration in the bulk. The combination of surface characterisation techniques and bulk studies indicate that interfacial film formation is preferred over bulk aggregation. This observation at the air/water interface supports the Derjaguin prediction, that a sphere's interaction with a plane (the thick adsorbed nanogel layer at interface) is much larger than nanogel-nanogel (sphere-sphere) association in the bulk. These findings, in particular the changes in conformations and the thick layer adsorption at the interface as a function of concentration, impact significantly on a number of applications for which nanogels are currently being investigated. These results contribute to the understanding of the behaviour of soft colloids at the interfaces.

Forest roadsides harbour less competitive habitats for a relict mountain plant (Pulsatilla vernalis) in lowlands.

The long-term survival of relict populations depends on the accessibility of appropriate sites (microrefugia). In recent times, due to the mass extinction of rare species that has resulted from the loss of natural habitats, the question is - Are there any human-made sites that can act as refugial habitats? We examined forest roadside populations of the mountain plant Pulsatilla vernalis in the last large lowland refugium in Central Europe. We compared the habitat conditions and community structure of roadsides with P. vernalis against the forest interior. Light availability and bryophyte composition were the main factors that distinguished roadsides. Pulsatilla occurred on sites that had more light than the forest interior, but were also more or less shaded by trees, so more light came as one-side illumination from the road. Roadsides had also a lower coverage of bryophytes that formed large, dense carpets. At the same time, they were characterised by a greater richness of vascular plants and 'small' bryophytes, which corresponds to a higher frequency of disturbances. In a warming and more fertile Anthropocene world, competition plays the main role in the transformation of forest communities, which is why relict populations have found refugia in extensively disturbed human-made habitats.

A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura skeletal dysplasia due to pathogenic variants in ALG9.

A rare lethal autosomal recessive syndrome with skeletal dysplasia, polycystic kidneys and multiple malformations was first described by Gillessen-Kaesbach et al and subsequently by Nishimura et al. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. We studied two unrelated families including three affected fetuses with Gillessen-Kaesbach-Nishimura syndrome using whole-exome and Sanger sequencing, comparative genome hybridization and homozygosity mapping. All affected patients were shown to have a novel homozygous splice variant NM_024740.2: c.1173+2T>A in the ALG9 gene, encoding alpha-1,2-mannosyltransferase, involved in the formation of the lipid-linked oligosaccharide precursor of N-glycosylation. RNA analysis demonstrated skipping of exon 10, leading to shorter RNA. Mass spectrometric analysis showed an increase in monoglycosylated transferrin as compared with control tissues, confirming that this is a congenital disorder of glycosylation (CDG). Only three liveborn children with ALG9-CDG have been previously reported, all with missense variants. All three suffered from intellectual disability, muscular hypotonia, microcephaly and renal cysts, but none had skeletal dysplasia. Our study shows that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia with visceral malformations as the most severe phenotype. The skeletal features overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that this subset of glycosylation disorders constitutes a new diagnostic group of skeletal dysplasias.