Geometric Morphometric Analysis of the Pedal Claw of the Early Cretaceous Bird Confuciusornis sanctus (Confuciusornithidae) and Its Functional and Behavioral Implications

onfuciusornis sanctus (Hou et al., 1995) is an Early Cretaceous bird from the Liaoning Province of northeastern China. Much work has been published on this species, but some details of its habitat and behavior remain unclear. In this study, a geometric morphometric analysis of the ungual of the second pedal digit of Confuciusornis sanctus was performed to determine how its morphology compares to that of extant birds and which morphological variables best distinguish between taxonomic and behavioral groups. A total of 128 specimens was examined, comprising 104 extant bird species across 15 orders and Confuciusornis sanctus. Three fixed landmarks and 50 sliding semilandmarks were used to define shape. A principal component analysis gave two axes explaining over 73% of the variation in shape. Principal component one, which varies in the angle of claw curvature, explains 56% of the morphological variation whereas principal component two, which varies in claw thickness, explains 17.44%. Specimens are relatively evenly spread across principal component one. There is a large amount of overlap between specimen groups across principal component two. When principal component one is plotted against centroid size, specimen groups become more distinguishable. When specimens are grouped by order, groups show a large amount of overlap, indicating that taxonomic order is not strongly correlated with pedal claw morphology. Behavioral groups show much less overlap, indicating that differences in pedal claw morphology are more strongly correlated to behavior than ordinal-level taxonomic relationship. Additionally, claw curvature and claw size are the variables that are most correlated with differences in behavior, whereas claw thickness is not an informative morphological variable. The claw of Confuciusornis sanctus is morphologically similar to extant birds displaying arboreal behaviors. C. sanctus had the capability for short-term flight, and other aspects of the morphology of C. sanctus also support an arboreal lifestyle. The claw of C. sanctus also shows similarities to extant terrestrial birds. Other morphological characteristics suggest that it was not completely specialized for perching behavior, and it likely spent time on the ground as well as in the trees. Its claw morphology was dissimilar to that of extant birds of prey, indicating that it was unlikely that C. sanctus used its claws to seize prey. The pedal claw morphology of C. sanctus was most similar to that of Passer griseus, which inhabits woodland areas and feeds on seeds, grains, and small insects in trees and on the ground. It is likely that C. sanctus also fed on similar food sources. Its short, robust, toothless beak is ideal for a granivorous diet. However, it would have also been suited for piscivory. There is little direct evidence of its diet with the exception of a previously reported specimen preserving fish remains in the alimentary canal. This specimen combined with my study suggest that C. sanctus likely had an omnivorous diet, and elicits interesting questions about the evolution of the bird digestive system

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Search strategy.

The quality of medicines for the prevention and management of hypertensive disorders of pregnancy globally is a critical challenge in the reduction of maternal mortality rate. We aimed to conduct a systematic review of available studies on the quality of the eight medicines recommended globally for the prevention and management of hypertensive disorders of pregnancy. We searched five electronic databases- Ovid MEDLINE, EMBASE, CINAHL, ProQuest and Cochrane Library, and also grey literature, without year or language limitations. Any study assessing the quality parameters (Active Pharmaceutical Ingredients, pH, sterility, solubility, impurities) of medicines by using any valid laboratory methods was eligible. Two reviewers independently screened the studies, extracted data and applied Medicine Quality Assessment Reporting Guidelines tool for quality assessment. Results were narratively reported and stratified by the drug types. Of 5669 citations screened, 33 studies from 27 countries were included. Five studies reported on the quality of magnesium sulphate—two (Nigeria and USA) found substandard medicine due to failing API specification and contaminants, respectively. Another study from Nigeria and a multi-country study (10 lower-middle- and low-income countries) found poor-quality due to failing the pH criteria. Seven of eight studies evaluating aspirin found quality issues, including degraded medicines in five studies (Brazil, USA, Yugoslavia and Pakistan). Five studies of calcium supplements found quality issues, particularly heavy metal contamination. Of 15 antihypertensives quality studies, 12 found substandard medicines and one study identified counterfeit medicines. This systematic review identified pervasive issues of poor-quality medicines across all recommended medicines used to prevent or treat hypertensive disorders of pregnancy, raising concerns regarding their safety and effectiveness.</div

Characteristics and findings on studies of quality of calcium supplements.

Characteristics and findings on studies of quality of calcium supplements.</p

Characteristics and findings on studies of quality of aspirin.

Characteristics and findings on studies of quality of aspirin.</p

PRISMA Flow diagram illustrating the process of study identification and selection.

PRISMA Flow diagram illustrating the process of study identification and selection.</p

Recommended medicines for the prevention and treatment of hypertensive disorders of pregnancy.

Recommended medicines for the prevention and treatment of hypertensive disorders of pregnancy.</p

Characteristics and findings on studies of quality of antihypertensive medicines.

Characteristics and findings on studies of quality of antihypertensive medicines.</p