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Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer – Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR=2, 6) and 209 (28%) of premenopausal women had had a recent birth (less than three years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, (1%-9%)). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (

OBJECTIVE There are concerns regarding the risks of mid-urethral slings (MUS) for stress urinary incontinence (SUI), particularly because of the lack of long-term data. We compare patient-reported outcomes of a multicentre randomised controlled trial of retropubic (TVT, GYNECARE™) versus transobturator (TOT, MONARC™) tape surgery at 12 years. DESIGN AND SETTING A multicentre study was performed in 11 tertiary referral centres. POPULATION A cohort of 180 participants from the original trial, the majority of whom had mixed urinary incontinence. METHODS Postal questionnaire survey of patient-reported outcome measures using the International Consultation on Incontinence Questionnaire, Patient Global Impression of Improvement questionnaire (PGI-I) and a numeric rating scale pain questionnaire. MAIN OUTCOME MEASURES Comparison of the efficacy and complications between the TVT and TOT procedures in the long term. RESULTS A total of 110/180 responses were received: 55 for TVT and 55 for TOT. The mean follow-up was 12.8 ± 0.29 years (SD). TVT was significantly superior to TOT: 41.8% TVT with no SUI, versus 21.8% TOT (P = 0.04). Urgency urinary incontinence (UUI) was the most bothersome urinary symptom: 14.5% of respondents reported UUI after TVT and TOT. This was an improvement from the baseline levels: 61.8% TVT and 76.4% TOT. Seventeen patients (9 TVT and 8 TOT) out of 121 reported moderate or severe pain with severe pain in 3 with TVT and 2 with TOT. Overall, 80% TVT and 77% TOT participants reported their symptoms as improved on the PGI-I. CONCLUSIONS TVT is superior to TOT for SUI cure. Efficacy is reduced by 12 years. There is low incidence of severe vaginal or groin pain. Careful patient counselling on long-term outcomes is required. The Retropubic tape appears to be an effective treatment for the majority of women with SUI. TWEETABLE ABSTRACT Retropubic tape has superior efficacy to transobturator tape. Complications are comparable with low rates.

An extremely preterm infant presented with clinical and radiological features of Robinow syndrome including butterfly vertebrae, posterior rib fusion, brachydactyly, nail hypoplasia, and retromicrognathia resulting in difficult endotracheal intubation in the intensive care setting. Rapid trio exome sequencing detected a novel homozygous likely pathogenic missense variant in the ROR2 gene, NM_004560.3:c.950A>G, p.(Tyr317Cys), for which both parents were heterozygous carriers. In-silico protein modeling predicted a deleterious effect on the function of the protein. We report an extreme premature infant with novel homozygous likely pathogenic variant in the ROR2 gene consistent with autosomal recessive Robinow syndrome. This case expands the phenotypic and genotypic spectrum of this disorder and highlights the benefit of performing rapid exome sequencing early during evaluation to aid in patient management and providing accurate genetic counseling to families.

Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD-H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD-H has been associated with variants confined to a specific intra-genic locus involving Exon 7, suggesting that AIFM1 plays an important role in bone development and metabolism as well as cerebral myelination. Here we describe two further affected boys, one with a novel intronic variant associated with skipping of Exon 7 of AIFM1 and the other a synonymous variant within Exon 7 of AIFM1. We describe their clinical course and radiological and genetic findings, providing further insight into the natural history of this condition.

Short-rib polydactyly syndromes are a heterogeneous group of disorders characterized by narrow thorax with short ribs, polydactyly and often other visceral and skeletal malformations. To date there have only been six reported patients with homozygous and compound heterozygous variants in IFT81, causing a short-rib thoracic dysplasia, with, or without, polydactyly (SRTD19: OMIM 617895). IFT81 is a protein integral to the core of the intraflagellar transport complex B (IFT-B), which is involved in anterograde transport in the cilium. We describe the case of a male infant with compound heterozygous variants in IFT81, who presented with short long bones, a narrow thorax, polydactyly, and multiple malformations. Three novel clinical features are reported including complete situs inversus, micropenis, and rectal atresia, which have not previously been associated with variants in IFT81. We reviewed the literature and identified the most consistent clinical features associated with this rare ciliopathy syndrome. We postulate that dolichocephaly and sagittal craniosynostosis may be associated with this condition, and provide a clue to considering IFT81 as the causative gene when deciphering complex ciliopathies.

Objective:\ud There are concerns regarding the risks of mid-urethral slings (MUS) for stress urinary incontinence (SUI), particularly because of the lack of long-term data. We compare patient-reported outcomes of a multicentre randomised controlled trial of retropubic (TVT, GYNECARE™) versus transobturator (TOT, MONARC™) tape surgery at 12 years.\ud \ud Design and setting:\ud A multicentre study was performed in 11 tertiary referral centres.\ud \ud Population:\ud A cohort of 180 participants from the original trial, the majority of whom had mixed urinary incontinence.\ud \ud Methods:\ud Postal questionnaire survey of patient-reported outcome measures using the International Consultation on Incontinence Questionnaire, Patient Global Impression of Improvement questionnaire (PGI-I) and a numeric rating scale pain questionnaire.\ud \ud Main outcome measures:\ud Comparison of the efficacy and complications between the TVT and TOT procedures in the long term.\ud \ud Results:\ud A total of 110/180 responses were received: 55 for TVT and 55 for TOT. The mean follow-up was 12.8 ± 0.29 years (SD). TVT was significantly superior to TOT: 41.8% TVT with no SUI, versus 21.8% TOT (P = 0.04). Urgency urinary incontinence (UUI) was the most bothersome urinary symptom: 14.5% of respondents reported UUI after TVT and TOT. This was an improvement from the baseline levels: 61.8% TVT and 76.4% TOT. Seventeen patients (9 TVT and 8 TOT) out of 121 reported moderate or severe pain with severe pain in 3 with TVT and 2 with TOT. Overall, 80% TVT and 77% TOT participants reported their symptoms as improved on the PGI-I.\ud \ud Conclusions:\ud TVT is superior to TOT for SUI cure. Efficacy is reduced by 12 years. There is low incidence of severe vaginal or groin pain. Careful patient counselling on long-term outcomes is required. The Retropubic tape appears to be an effective treatment for the majority of women with SUI.\ud \ud Tweetable abstract:\ud Retropubic tape has superior efficacy to transobturator tape. Complications are comparable with low rates.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.

Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD‐H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD‐H has been associated with variants confined to a specific intra‐genic locus involving Exon 7, suggesting that AIFM1 plays an important role in bone development and metabolism as well as cerebral myelination. Here we describe two further affected boys, one with a novel intronic variant associated with skipping of Exon 7 of AIFM1 and the other a synonymous variant within Exon 7 of AIFM1. We describe their clinical course and radiological and genetic findings, providing further insight into the natural history of this condition.

HR‐pQCT is a non‐invasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (i) assess fracture‐associated differences in HR‐pQCT bone parameters and (ii) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291‐3253 and 3389‐10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% CI: −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI: −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD, and certain tibial cortical parameters, can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction.

OBJECTIVE: Mutations in the aggrecan gene (ACAN) have been identified in two autosomal dominant skeletal dysplasias, spondyloepiphyseal dysplasia, Kimberley type (SEDK), and osteochondritis dissecans, as well as in a severe recessive dysplasia, spondyloepimetaphyseal dysplasia, aggrecan type. Next-generation sequencing (NGS) has aided the identification of heterozygous ACAN mutations in individuals with short stature, minor skeletal defects and mild facial dysmorphisms, some of whom have advanced bone age (BA), poor pubertal spurt and early growth cessation as well as precocious osteoarthritis. DESIGN AND METHODS: This study involves clinical and genetic characterization of 16 probands with heterozygous ACAN variants, 14 with short stature and mild skeletal defects (group 1) and two with SEDK (group 2). Subsequently, we reviewed the literature to determine the frequency of the different clinical characteristics in ACAN-positive individuals. RESULTS: A total of 16 ACAN variants were located throughout the gene, six pathogenic mutations and 10 variants of unknown significance (VUS). Interestingly, brachydactyly was observed in all probands. Probands from group 1 with a pathogenic mutation tended to be shorter, and 60% had an advanced BA compared to 0% in those with a VUS. A higher incidence of coxa valga was observed in individuals with a VUS (37% vs 0%). Nevertheless, other features were present at similar frequencies. CONCLUSIONS: ACAN should be considered as a candidate gene in patients with short stature and minor skeletal defects, particularly those with brachydactyly, and in patients with spondyloepiphyseal dysplasia. It is also important to note that advanced BA and osteoarticular complications are not obligatory conditions for aggrecanopathies/aggrecan-associated dysplasias. info:eu-repo/semantics/publishedVersion

Breast cancer (BC) survival rates in sub-Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting-specific drivers of advanced stage BC. Women newly diagnosed in the multi-country African Breast Cancer - Disparities in Outcomes (ABC-DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman-level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multi-racial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended

Processing of Precursor 1 (POP1) is a large protein common to the ribonuclease-mitochondrial RNA processing (RNase-MRP) and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage-hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals show the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

Albright hereditary osteodystrophy (AHO) is a complex disorder defined by the presence of a short adult stature relative to the height of an unaffected parent and brachydactyly type E, as well as a stocky build, round face, and ectopic calcifications. AHO and pseudohypoparathyroidism (PHP) have been used interchangeably in the past. The term PHP describes end-organ resistance to parathyroid hormone (PTH), occurring with or without the physical features of AHO. Conversely, pseudopseudohypoparathyroidism (PPHP) describes individuals with AHO features in the absence of PTH resistance. PHP and PPHP are etiologically linked and caused by genetic and/or epigenetic alterations in the guanine nucleotide-binding protein alpha-stimulating (Gs α) locus (GNAS) in chromosome 20q13. Another less-recognized group of skeletal dysplasias, termed acrodysostosis, partially overlap with skeletal, endocrine, and neurodevelopmental features of AHO/PHP and can be overlooked in clinical practice, causing confusion in the literature. Acrodysostosis is caused by defects in two genes, PRKAR1A and PDE4D, both encoding important components of the Gs α-cyclic adenosine monophosphate-protein kinase A signaling pathway. We describe the clinical course and genotype of two adult patients with overlapping AHO features who harbored novel pathogenic variants in GNAS (c.2273C > G, p.Pro758Arg, NM_080425.2) and PRKAR1A (c.803C > T, p.Ala268Val, NM_002734.4), respectively. We highlight the value of expert radiological opinion and molecular testing in establishing correct diagnoses and discuss phenotypic features of our patients, including the first description of subcutaneous ossification and spina bifida occulta in PRKAR1A-related acrodysostosis, in the context of the novel inactivating PTH/PTH related peptide signaling disorder classification system.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.

In 1987, Cole and Carpenter reported two unrelated infants with multiple fractures and deformities of bone, with a skeletal phenotype similar to severe osteogenesis imperfecta. In addition, these patients also had proptosis, blue sclerae, hydrocephalus, and a distinct facial gestalt. They were reported to be of normal intelligence. Radiologically, these patients had characteristic skeletal manifestations including craniosynostosis and deformities similar to severe progressive osteogenesis imperfecta. Since the first description, there have only been a few other reports of patients with a similar phenotype. Collagen studies performed in reported patients have been normal. The molecular basis of this syndrome has not been elucidated and the inheritance pattern is still unknown. We report on a child with Cole-Carpenter syndrome phenotype who has a homozygous c.118G>T mutation in exon 1 of the CRTAP gene. We describe the clinical features and correlate this with her molecular results. This is the first report towards elucidating the molecular basis of Cole-Carpenter syndrome. © 2015 Wiley Periodicals, Inc.

POP1 is a large protein common to the RNase-MRP and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8 s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals demonstrate the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

Objectives The aim of this study was to compare the diagnostic accuracy of postmortem magnetic resonance (PMMR) imaging specifically for musculoskeletal pathology in fetuses and children, compared with conventional autopsy, with radiographic and histopathology assessment. Methods Institutional ethics approval and parental consent was obtained. A total of 400 cases underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data, respectively. Results A total of 400 cases were reported, with 277 (69%) fetuses (185 ≤24 weeks' gestation and 92 >24 weeks' gestation) and 123 children (42 newborns aged

Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies. Prenatal ultrasound scanning is a useful tool to detect several skeletal dysplasias and sonographic measurements serve as reliable indicators of lethality. The lethality depends on various factors including gestational age at which features are identified, size of the chest and progression of malformations. Although, it is important to type the skeletal presentation as accurately as possible, this is not always possible in an antenatal presentation and it is important to acknowledge this uncertainty. In the case of a live birth, it is always important to reassess the infant. Osteogenesis imperfecta (OI) is a heterogeneous group of disorders characterized by fragile bones. Here, we report an infant with severe OI born following a twin pregnancy in whom the bone disease is caused by a heterozygous pathogenic mutation, c.4160C >T, p.(Ala1387Val) located in the C-propeptide region of COL1A1. An assumption of lethality antenatally complicated his management in early life. We discuss this patient with particular emphasis on the neonatal presentation of a severe skeletal dysplasia and the lessons that may be learned in such situations. © 2016 Wiley Periodicals, Inc.

The accuracy of biomechanical simulation has been improved by using high-resolution computed tomography (CT) to define the geometry and material parameters. This technique has been used to assess numerous systems, including the mechanical properties of bone, fixation techniques post-fracture and the performance of bone microarchitecture. In this study, a semi-automated process for converting CT data into finite element (FE) models was used to model the mid-shaft (diaphysis) of porcine femoral samples under sub-maximal torsional and compressive load. Physical validation was undertaken to investigate if the all-important geometry and material property mapping functioned correctly. Porcine femoral specimens were imaged using contiguous helical CT, which was converted to FE models using ScanIP from Simpleware, Exeter, UK. The heterogeneous material properties were estimated using density–elasticity relationships proposed in literature for human bone samples. Laboratory testing performed favourably, with a linear strain response validating the use of the array of linear material models used in simulation. The simulation procedure also performed well. Linear regression and mean error calculation demonstrated accurate correlation between predicted (from simulation) and observed (measured within the laboratory) results that offered improvement over the accuracy within comparative testing for human samples. Using FE modelling on a patient-specific basis offers potential in a number of scenarios, including the determination of injury risk and design of protective equipment. The increased accessibility of animal samples allows large-scale fracture testing of complex loading mechanisms and the potential to consider younger animal samples (to investigate the behaviour of developing bone). Spiral fractures of long bones have been demonstrated to be an indicator of non-accidental injury in children. Combining the increased accuracy in torsional simulation in this study with younger sample testing may be employed to attempt to determine the causes of fracture from post fracture scans, aiding in the diagnosis of non-accidental injury.

Striking Phenotypic Variability in Familial TRPV4-Axonal Neuropathy Spectrum Disorder Sharon Aharoni, Gaurav Harlalka, Amaka Offiah, Avinoam Shuper, Andrew H. Crosby, and Meriel McEntagart* Department of Neurology, Schneider Children’s Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Centre for Medical Genetics, St. George’s University London, London, UK Academic Unit of Child Health, Sheffield Children’s NHS Foundation Trust, Sheffield, UK

Uniparental disomy (UPD) for chromosome 14 is associated with well-recognized phenotypes, depending on the parent of origin. Studies in mouse models and human patients have implicated the involvement of the distal region of the long arm of chromosome 14 in the distinctive phenotypes. This involvement is supported by the identification of an imprinting cluster at chromosome 14q32, encompassing the differentially methylated regions (DMRs), IG-DMR and MEG3-DMR, as well as the maternally expressed genes GTL2, DIO3, and RTL1 and the paternally expressed genes DLK1, RTL1as, and MEG8. Here we report on a preterm female infant with distal segmental paternal UPD14 (upd(14)pat) of 14q32-14q32.33, which resulted in thoracic deformity secondary to rib abnormalities ("coat-hanger" rib sign), polyhydramnios, and other congenital abnormalities characteristically described in cases of complete upd(14)pat. Microsatellite investigation demonstrated UPD of markers D14S250 and D14S1010, encompassing a approximately 3.5 Mb region of distal 14q and involving the imprinting cluster. This case provided insight into the etiology of the phenotypic effects of upd(14)pat, prompting methylation analysis of the GTL2 promoter and the DMR between GTL2 and DLK1. We compare the physical findings seen in this case with those of patients with other causes of abnormal methylation of 14q32, which consistently result in certain distinct clinical features, regardless of the cytogenetic and molecular etiology.

In Southern Nigeria, the leaves of Emilia coccinea (Sims) G Dons are used traditionally for birth control. This study was therefore aimed at evaluating the activities of the methanolic leaf extract of Emilia coccinea (EM) on parameters that affect reproduction as well as the acute toxic effects of the plant using nonpregnant female mice models. Leaves of EM were extracted by maceration with 99.8% methanol. Oral acute toxicity profiles were examined. The effects of EM on female reproductive cycle were determined after oral treatment with EM at 1000 and 100 mg/kg/day daily for 6 days using stilbesterol (1 mg/kg/day) and normal saline as controls. The activities of EM (1000 mg/kg/day and 100 mg/kg/day p.o) on reproductive hormones and organs were also studied using estradiol valerat (100 mg/kg/day p.o), progesterone (10 mg/kg/day s.c.), and normal saline as controls. The extract did not induce any observable toxic effect after 24 h. At 1000 mg/kg, the extract significantly shortened the estrus cycle (P

The accuracy of biomechanical simulation has been improved by using high-resolution computed tomography (CT) to define the geometry and material parameters. This technique has been used to assess numerous systems, including the mechanical properties of bone, fixation techniques post-fracture and the performance of bone microarchitecture. In this study, a semi-automated process for converting CT data into finite element (FE) models was used to model the mid-shaft (diaphysis) of porcine femoral samples under sub-maximal torsional and compressive load. Physical validation was undertaken to investigate if the all-important geometry and material property mapping functioned correctly. Porcine femoral specimens were imaged using contiguous helical CT, which was converted to FE models using ScanIP from Simpleware, Exeter, UK. The heterogeneous material properties were estimated using density–elasticity relationships proposed in literature for human bone samples. Laboratory testing performed favourably, with a linear strain response validating the use of the array of linear material models used in simulation. The simulation procedure also performed well. Linear regression and mean error calculation demonstrated accurate correlation between predicted (from simulation) and observed (measured within the laboratory) results that offered improvement over the accuracy within comparative testing for human samples. Using FE modelling on a patient-specific basis offers potential in a number of scenarios, including the determination of injury risk and design of protective equipment. The increased accessibility of animal samples allows large-scale fracture testing of complex loading mechanisms and the potential to consider younger animal samples (to investigate the behaviour of developing bone). Spiral fractures of long bones have been demonstrated to be an indicator of non-accidental injury in children. Combining the increased accuracy in torsional simulation in this study with younger sample testing may be employed to attempt to determine the causes of fracture from post fracture scans, aiding in the diagnosis of non-accidental injury.

Reclamation of acid sulfate soils requires the use of lining materials. SWAN-gypsum (secondary waste acid neutralization gypsum), a waste from a sulfuric acid, titanium oxide refining process, contains {approximately}10% CaCO{sub 3}, as well as CaSO{sub 4}{center_dot}2 H{sub 2}O (gypsum) and Fe oxides. This material was tested via laboratory incubation studies in comparison to laboratory grade CaCO{sub 3} as a liming material for a silty clay material from a Typic Sulfaquept formed on dredged materials. A batch titration method (by shaking a set of soil samples amended with various levels of a potential liming material) was also tested. The ability of SWAN-gypsum to raise soil pH was comparable to its CaCO{sub 3} content. The CaCO{sub 3} occurs as unreacted aragonite that is Fe oxide coated as a result of the acid neutralization process that produces the waste. Gypsum and Fe oxides, also present in the waste, were shown to have little or no liming value with the soil material employed. Batch titration (open system, 24 h shaking) gave neutralization results similar to those from regular incubation for 45 d. The pH values achieved with increasing levels of SWAN-gypsum were lower with closed than with open systems at pH values above 6.6more » (by 0.1 to 0.45 pH units, presumbly due in part to differences in CO{sub 2} pressure), but higher with the closed system at lower pH values (by 0.2 to 2.3 pH units, perhaps due to oxidation of sulfides with the open system). At pHs below neutral following open batch titration, pHs measured before drying the materials, were higher than those measured after drying and rewetting by 0.2 to 1.5 pH units, whereas they were slightly lower before drying, by up to 0.2 pH units, at pHs above neutral. The methods reported for testing the liming value of this waste should have value in testing the liming value of other potential acid neutralizing materials. 16 refs., 9 figs.« less

Existing nomenclature systems for describing and reporting congenital segmentation defects of the vertebrae (SDV) are confusing, inconsistently applied, and lack molecular genetic advances. Our aim was to develop and assess a new classification system for SDV. A multidisciplinary group of the International Consortium for Vertebral Anomalies and Scoliosis (ICVAS) developed a new classification system for SDV, and 5 members group (Group 1) independently classified 10 previously unseen cases using this system. Inter-observer reliability was assessed using kappa, which compares observed agreement with that expected by chance. Seven independent general radiologists unaffiliated with the ICVAS (Group 2) classified the same 10 cases (total, 70 scores) before and after the ICVAS system was explained. We demonstrated the following: Inter-observer reliability for Group 1 yielded a kappa value of 0.21 (95% confidence intervals (CI) 0.052, 0.366, P = 0.0046); A consensus diagnosis was established for the 10 cases. For Group 2, before the ICVAS system was explained, 1 of 70 scores (1.4%) agreed with the Group 1 consensus diagnoses; Group 2 offered 12 different diagnoses, but 38 of 70 (54.3%) responses were “Don't Know.” After the ICVAS system was explained, 47 of 70 responses (67.1%; 95% CI 55.5, 77.0) agreed with the Group 1 consensus, an improvement of 65.7% (95% CI 52.5, 75.6, P