Orphaned Trainees: A Vulnerable Population in an Inequitable System.

Two years ago, Hahnemann University Hospital (HUH) closed, orphaning the largest group of trainees in the history of graduate medical education (GME). Last month, the plastic surgery community learned of the forthcoming closure of two plastic surgical residencies (2.4% of all integrated plastic surgery residencies), while most programs were in the final stages of planning the 2021-2022 academic year. Recounting the turmoil experienced by orphaned HUH trainees and their families, left alone to relocate amidst funding-related legal battles, one cannot help but wonder, how could this happen again? Trainees deserve transparency, funding protection and support when training programs close or lose accreditation. Moreover, applicants deserve to know if a program is on the brink of collapse before they sign their rank list. Applicants and trainees deserve to have their funding protected in the event of a program closure, so their ability to relocate is not held hostage by a sponsoring institution. Trainees deserve to be supported by a central organization that is responsible their relocation in the event of an orphanage. These changes are overdue and their absence has already resulted in academic and emotional adversities for trainees and their families.

A new absolute date from Swartkrans Cave for the oldest occurrences of Paranthropus robustus and Oldowan stone tools in South Africa.

The Early Pleistocene site of Swartkrans in South Africa's Cradle of Humankind World Heritage Site has been significant for our understanding of the evolution of both early Homo and Paranthropus, as well as the earliest archaeology of southern Africa. Previous attempts to improve a faunal age estimate of the earliest deposit, Member 1, had produced results obtained with uranium-lead dating (U-Pb) on flowstones and cosmogenic burial dating of quartz, which placed the entire member in the range of >1.7/1.8 Ma and <2.3 Ma. In 2014, two simple burial dates for the Lower Bank, the earliest unit within Member 1, narrowed its age to between ca. 1.8 Ma and 2.2 Ma. A new dating program using the isochron method for burial dating has established an absolute age of 2.22 ± 0.09 Ma for a large portion of the Lower Bank, which can now be identified as containing the earliest Oldowan stone tools and fossils of Paranthropus robustus in South Africa. This date agrees within one sigma with the U-Pb age of 2.25 ± 0.08 Ma previously published for the flowstone underlying the Lower Bank and confirms a relatively rapid rate of accumulation for a large portion of the talus.

Fatty acid binding protein-4 is associated with disability in multiple sclerosis patients.

BACKGROUND: Increased adiposity is a risk factor for multiple sclerosis (MS) and is associated with increased disability scores. Adipokines may mediate the effects of adiposity on MS disease course. OBJECTIVE: The objective of this study is to examine the association between the adipokines (leptin and fatty acid binding protein-4, FABP4) and clinical course in individuals with MS. METHODS: Subjects (18-65 years) with relapsing-remitting MS or clinically isolated syndrome and <10 year disease duration were selected from a longitudinal clinical study. Cross-sectional and longitudinal models assessed the relationship between two adipokines (leptin and FABP4) and disease severity in women and men, adjusting for age, disease duration and disease type, Vitamin D level, testosterone level, and as well by body mass index (BMI). RESULTS: Mean age of subjects ( N = 163, 56% women) was 39.3 years. Higher FABP4 levels were associated with higher Expanded Disability Status Scale (EDSS) scores in women in both univariate and multivariate analyses (odds ratio: 1.30; p = 0.005). In men, higher FABP4 level was significantly associated with change in EDSS over time (estimate: 0.0062; p = 0.035). We found no association of FABP4 levels with time to next relapse or a measure of processing speed. CONCLUSION: FABP4 levels may be associated with increased disability in both men and women with MS independent of effects of BMI and other hormones. Future studies should expand these analyses and further explore downstream mechanisms of adiposity-related effects in MS.

Elemental formula associated hypophosphataemic rickets.

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2.

BACKGROUND: In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. METHODS: This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK. American Thyroid Association (ATA) 2009 guidelines were used as a benchmark for adequate treatment. RESULTS: Seventy-nine children from 16 centres underwent total thyroidectomy. Thirty-eight patients (48 per cent) underwent genetic testing and 36 (46 per cent) had an operation performed above the age recommended by the ATA 2009 guidelines; pathology showed MTC in 30 patients (38 per cent). Late surgery, above-normal preoperative calcitonin level and MTC on pathology correlated with late genetic testing. Twenty-five children had lymphadenectomy; these patients had more parathyroid glands excised (mean difference 0·61, 95 per cent c.i. 0·24 to 0·98; P = 0·001), and were more likely to have hypocalcaemia requiring medication (relative risk (RR) 3·12, 95 per cent c.i. 1·54 to 6·32; P = 0·002) and permanent hypoparathyroidism (RR 3·24, 1·29 to 8·11; P = 0·010) compared with those who underwent total thyroidectomy alone. Age did not influence the development of complications. CONCLUSION: Late genetic testing may preclude age-appropriate surgery, increasing the risk of operating when MTC has already developed. Early genetic testing and age-appropriate surgery may help avoid unnecessary lymphadenectomy and improve outcomes.

Bone health and SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. We report molecular and phenotypic features of 7 individuals with SAS documented to have low bone mineral density (BMD) ascertained by dual-energy X-ray absorptiometry (DXA), often preceded by tibial bowing. The lowest BMD Z-scores ranged -2.3 to -5.6. In 4 individuals, total alkaline phosphatase levels were elevated (2 with elevated bone fraction) around the time of low BMD documentation. A clinically significant fracture history and a diagnosis of pediatric osteoporosis were present in 4 individuals. Pamidronate treatment in 2 children improved BMD. In conclusion, low BMD, fractures, and tibial bowing are relatively common skeletal complications in individuals with SAS. DXA is a useful tool when evaluating a child with SAS suspected to have low BMD and the results might alter clinical management.

New early Pleistocene hominin teeth from the Swartkrans Formation, South Africa.

We describe 14 hominin teeth and tooth fragments excavated recently from Swartkrans Cave (South Africa). The fossils derive from Members 1 (Lower Bank) and 3, from the Member 2/3 interface and from two deposits not yet assigned to member (the "Talus Cone Deposit" and the "Underground North Excavation" [UNE]) of the Swartkrans Formation, and include the first hominin fossil from the UNE, the two smallest Paranthropus robustus deciduous maxillary second molars in the entire hominin fossil record, and one of the smallest P. robustus permanent maxillary second molars from Swartkrans. The small permanent molar is accompanied by another tooth from a different individual but from the same stratigraphic level of the Swartkrans Formation; this second tooth is among, if not, the largest P. robustus permanent maxillary first molars known from anywhere-lending credence to assertions that degrees of body size sexual dimorphism previously ascribed to this species may be underestimated. It is more equivocal whether this evidence also supports hypotheses proposing that P. robustus assemblages from Swartkrans (as well as those from other South African cave sites) formed through the taphonomically biasing actions of large carnivores.

Identification, inheritance, and fitness costs of Cry2Ab2 resistance in a field-derived population of sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae).

The sugarcane borer, Diatraea saccharalis (F.), is one of the major target pests of transgenic maize, Zea mays, expressing Bacillus thuringiensis (Bt) proteins in South America and mid-southern region of the U.S. The MON89034 maize expresses Cry2Ab2 and Cry1A.105 Bt proteins and it was developed to provide better control of key lepidopteran pests of maize including D. saccharalis. The objectives of this study were to select and characterize the resistance of D. saccharalis to Cry2Ab2 using a non-commercial Cry2Ab2 single gene Bt maize line. A Cry2Ab2-resistant strain (Cry2Ab2-RR) of D. saccharalis was established from 28 two-parent families collected from fields in northeast Louisiana, U.S. The Cry2Ab2-RR showed a high level of resistance to Cry2Ab2 in both diet-incorporated and whole maize plant bioassays. The Cry2Ab2 resistance in D. saccharalis was likely inherited as a single or a few tightly linked autosomal genes. The resistance was non-recessive and not associated with fitness costs. The results should provide valuable information in resistance monitoring, assessing resistance risk, and developing effective management strategies for the sustainable use of Bt maize technology for managing maize stalk borers.

Individual variation of isotopic niches in grazing and browsing desert ungulates.

Ungulates often adjust their diet when food availability varies over time. However, it is poorly understood when and to what extent individuals change their diet and, if they do so, if all individuals of a population occupy distinct or similar dietary niches. In the arid Namibian Kunene Region, we studied temporal variations of individual niches in grazing gemsbok (Oryx gazella gazella) and predominantly browsing springbok (Antidorcas marsupialis). We used variation in stable C and N isotope ratios of tail hair increments as proxies to estimate individual isotopic dietary niches and their temporal plasticity. Isotopic dietary niches of populations of the two species were mutually exclusive, but similar in breadth. Isotopic niche breadth of gemsbok was better explained by within-individual variation than by between-individual variation of stable isotope ratios, indicating that gemsbok individuals were facultative specialists in using isotopically distinct local food resources. In contrast, inter- and intra-individual variations contributed similarly to the isotopic niche breadth of the springbok population, suggesting a higher degree of individual isotopic segregation in a more generalist ungulate. In both species, between-individual variation was neither explained by changes in plant primary productivity, sex, geographical position nor by group size. Within species, individual dietary niches overlapped partially, suggesting that both populations included individuals with distinct isotopic dietary niches. Our study provides the first evidence for isotopic dietary niche segregation in individuals of two distinct desert ungulates. Similar, yet isotopically distinct dietary niches of individuals may facilitate partitioning of food resources and thus individual survival in desert ecosystems.

Surgical treatment of children with hyperparathyroidism: single centre experience.

BACKGROUND: Hyperparathyroidism (HPT) in children is rare and surgical management is supported only by limited evidence. METHODS: Retrospective case series of all children under the age of 16 years who underwent parathyroidectomy (PTx) between 1978 and 2012. RESULTS: We identified 29 children who had surgery for HPT. Six were neonates with neonatal severe hyperparathyroidism (NSHPT) and 23 older children (age range 7-16 years) with sporadic (16) or familial (7) HPT and 93% were symptomatic. Accuracy of ultrasound and MIbi in localising solitary parathyroid adenomas was 96%, but less helpful in hyperplasia and neonates. Children with NSHPT underwent 5 curative total and 1 subtotal PTx (no reoperations). Children with familial HPT underwent 3 total and 4 subtotal PTx. One child with subtotal PTx required a reoperation. Children with sporadic HPT underwent subtotal PTx prior to 1980 (2), exploration and removal of enlarged glands 1980-2002 (5) and minimally invasive PTx since 2002 (9) and all cured by the first operation. CONCLUSIONS: Our study documents that HPT in children is predominantly symptomatic on presentation and genetically determined in 46% of cases. Imaging is accurate in localising parathyroid adenomas, but not hyperplasias. Total PTx for familial HPT was curative and minimally invasive PTx is the operation of choice for older children with sporadic HPT.

Single-chain factor XII exhibits activity when complexed to polyphosphate.

BACKGROUND: The mechanism underpinning factor XII autoactivation was originally characterized with non-physiological surfaces, such as dextran sulfate (DS), ellagic acid, and kaolin. Several 'natural' anionic activating surfaces, such as platelet polyphosphate (polyP), have now been identified. OBJECTIVE: To analyze the autoactivation of FXII by polyP of a similar length to that found in platelets (polyP70 ). METHODS AND RESULTS: PolyP70 showed similar efficacy to DS in stimulating autoactivation of FXII, as detected with amidolytic substrate. Western blotting revealed different forms of FXII with the two activating surfaces: two-chain αFXIIa was formed with DS, whereas single-chain FXII (scFXII; 80 kDa) was formed with polyP70 . Dissociation of scFXII from polyP70 abrogated amidolytic activity, suggesting reversible exposure of the active site. Activity of scFXII-polyP70 was enhanced by Zn(2+) and was sensitive to NaCl concentration. A bell-shaped concentration response to polyP70 was evident, as is typical of surface-mediated reactions. Reaction of scFXII-polyP70 with various concentrations of S2302 generated a sigmoidal curve, in contrast to a hyperbolic curve for αFXIIa, from which a Hill coefficient of 3.67 was derived, indicative of positive cooperative binding. scFXII-polyP70 was more sensitive to inhibition by H-d-Pro-Phe-Arg-chloromethylketone and corn trypsin inhibitor than αFXIIa, but inhibition profiles for C1-inhibitor were similar. Active scFXII-polyP70 was also able to cleave its physiological targets FXI and prekallikrein to their active forms. CONCLUSIONS: Autoactivation of FXII by polyP, of the size found in platelets, proceeds via an active single-chain intermediate. scFXII-polyP70 shows activity towards physiological substrates, and may represent the primary event in initiating contact activation in vivo.

Personal protective equipment use among students with special health care needs reporting injuries in school-sponsored vocational, career, and technical education programs in New Jersey.

Students with special health care needs (SHCNs) and individualized education plans (IEPs) may be injured more often in vocational, career, and technical education (CTE) programs. No research to date considers personal protective equipment (PPE) use among students with SHCNs in school-based programs reporting injuries to agencies. Data from 1999 to 2011 on PPE use among injured students in CTE programs in public schools and private secondary schools for the disabled were analyzed; students with SHCNs were distinguished by IEP status within New Jersey Safe Schools surveilance data. Among students with IEPs using PPE, 36% of injuries occurred to body parts PPE was meant to protect. Likely injury types were cuts-lacerations and burns for students with IEPs using PPE and cuts-lacerations and sprains for students with IEPs not using PPE. Females with IEPs using PPE were injured less often than males across ages. Results suggested students with SHCNs with IEPs need further job-related training with increased emphasis on properly selecting and fitting PPE.

New hominid fossils from Member 1 of the Swartkrans formation, South Africa.

Member 1 of the Swartkrans Formation is comprised of two sedimentary infills, the Lower Bank (LB) and the Hanging Remnant (HR). Together, the LB and HR preserve fossils of early Homo and Paranthropus robustus, Earlier Stone Age lithic artifacts, purported bone digging tools and butchered animal bones. Collectively, this evidence was the first to establish the co-existence of two early Pleistocene hominid species and also led to inferences of plant root harvesting and meat-eating by one or both of those species. P. robustus is the more abundant of the two hominids at Swartrkrans, represented in Member 1 by hundreds of fossils that derive from at least 99 individuals. Thus, Swartkrans Member 1 stands as the world's single largest repository of that extinct species. Here we add to the Member 1 sample of hominid fossils with descriptions of 14 newly discovered specimens.

Newly discovered fossil- and artifact-bearing deposits, uranium-series ages, and Plio-Pleistocene hominids at Swartkrans cave, South Africa.

We report on new research at Swartkrans Cave, South Africa, that provides evidence of two previously unrealized artifact- and fossil-bearing deposits. These deposits underlie a speleothem dated by the uranium-thorium disequilibrium technique to 110,000+/-1,980 years old, the first tightly constrained, geochronological date available for the site. Recovered fauna from the two underlying deposits-including, prominently, the dental remains of Paranthropus (Australopithecus) robustus from the uppermost layer (Talus Cone Deposit)-indicate a significantly older, late Pliocene or early Pleistocene age for these units. The lowest unit (LB East Extension) is inferred to be an eastward extension of the well-known Lower Bank of Member 1, the earliest surviving infill represented at the site. The date acquired from the speleothem also sets the maximum age of a rich Middle Stone Age lithic assemblage.

Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage.

Oxidative damage contributes to cone cell death in retinitis pigmentosa and death of rods, cones, and retinal pigmented epithelial (RPE) cells in age-related macular degeneration. In this study, we explored the strategy of overexpressing components of the endogenous antioxidant defense system to combat oxidative damage in RPE cells and retina. In transfected cultured RPE cells with increased expression of superoxide dismutase1 (SOD1) or SOD2, there was increased constitutive and stress-induced oxidative damage measured by the level of carbonyl adducts on proteins. In contrast, RPE cells with increased expression of glutathione peroxidase 1 (Gpx1) or Gpx4 did not show an increase in constitutive oxidative damage. An increase in Gpx4, and to a lesser extent Gpx1, reduced oxidative stress-induced RPE cell damage. Co-expression of Gpx4 with SOD1 or 2 partially reversed the deleterious effects of the SODs. Transgenic mice with inducible expression of Gpx4 in photoreceptors were generated, and in three models of oxidative damage-induced retinal degeneration, increased expression of Gpx4 provided strong protection of retinal structure and function. These data suggest that gene therapy approaches to augment the activity of Gpx4 in the retina and RPE should be considered in patients with retinitis pigmentosa or age-related macular degeneration.

Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life-threatening infant heart failure.

BACKGROUND: In recent large paediatric cardiomyopathy population studies from North America and Australia, vitamin D deficiency was not identified as a cause of infant heart failure. However, rickets is resurgent in developed countries. OBJECTIVE: To review the prevalence of this cardiomyopathy in paediatric cardiology units of southeast England and determine the prognosis. METHODS AND RESULTS: A retrospective review from 2000 to 2006 in southeast England. Sixteen infants (6 Indian subcontinent, 10 black ethnicity) were identified: median (range) age at presentation was 5.3 months (3 weeks-8 months). All had been breast fed. Ten presented at the end of the British winter (February-May). Median shortening fraction was 10% (range 5-18%) and median left ventricular end diastolic dimension z score was 4.1 (range 3.1-7.0). Six had a cardiac arrest; three infants died. Eight were ventilated, two required mechanical circulatory support and 12 required intravenous inotropic support. Two were referred for cardiac transplantation. Median (range) of biochemical values on admission was: total calcium 1.5 (1.07-1.74) mmol/l; alkaline phosphatase 646 (340-1057) IU/l; 25-hydroxyvitamin D 18.5 (0-46) nmol/l (normal range >35) and parathyroid hormone 34.3 (8.9-102) pmol/l (normal range <6.1). The clinical markers and echocardiographic indices of all survivors have improved. The mean time from diagnosis to achieve normal fractional shortening was 12.4 months. CONCLUSIONS: Vitamin D deficiency and consequent hypocalcaemia are seen in association with severe and life-threatening infant heart failure. That no infant or mother was receiving the recommended vitamin supplementation highlights the need for adequate provision of vitamin D to ethnic minority populations.

Bone mineralization in children with epidermolysis bullosa.

BACKGROUND: Various factors may have deleterious effects on bone health in patients with epidermolysis bullosa (EB). OBJECTIVES: In a retrospective notes review, to assess bone mineralization in children with EB and to identify the relative contributions of nutrition, activity and disease severity to low bone mass. METHODS: Thirty-nine children with EB [32 recessive dystrophic EB (RDEB), four Dowling-Meara EB simplex (DMEBS) and three junctional EB (JEB)] had lumbar spine bone mass measured using dual X-ray absorptiometry (GE Lunar Prodigy; GE Healthcare, Chalfont St Giles, U.K.). Seventy-six healthy children were also studied. Weight and height were recorded and mobility was rated. RESULTS: Children with RDEB and JEB, but not those with DMEBS, had lower bone mineral density SD scores than controls; differences remained after adjusting for the smaller body size of the patients. Bone mass was best predicted by mobility rating. CONCLUSIONS: Children with RDEB and JEB have low bone mass after adjusting for their smaller size, which may put them at risk for fragility fractures. Low bone mass was best predicted by the level of mobility, raising the hypothesis that improving activity or bone loading may be a potential preventive intervention in these children. However, as low bone mass may be multifactorial in these children, more detailed investigation of potential aetiological factors is required before interventions are planned.

Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing's disease.

BACKGROUND: Paediatric Cushing's disease (CD) is rare, but is associated with considerable morbidity and requires effective treatment. Control of hypercortisolaemia is recommended prior to definitive therapy by transsphenoidal pituitary surgery with selective adenomectomy. We describe a 6.2-year-old male with severe hypercortisolaemia and life-threatening complications of Cushing's disease. Control of cortisol with metyrapone and ketoconazole was ineffective, and due to his deteriorating condition, the decision was taken to proceed to bilateral adrenalectomy. METHODS: Low-dose IV infusion of etomidate, with dose titration according to serum cortisol levels, was administered. RESULTS: Etomidate infusion (3.0 mg/h i.v.) decreased serum cortisol from 1,250 to 250 nmol/l within 24 h. Combined etomidate and hydrocortisone therapy was maintained to provide stable serum cortisol levels within the desired range for 12 days prior to successful bilateral adrenalectomy. CONCLUSION: In our experience, etomidate was effective and safe for short-term control of severe hypercortisolaemia in a severely ill child.

Use of 3D imaging in CT of the acute trauma patient: impact of a PACS-based software package.

To evaluate the impact of a picture archiving and communication systems (PACS)-based software package on the requests for 3D reconstructions of multidetector CT (MDCT) data sets in the emergency radiology of a level 1 trauma center, we reviewed the number and type of physician requests for 3D reconstructions of MDCT data sets for patients admitted after sustaining multiple trauma, during a 12-month period (January 2003-December 2003). During the first 5 months of the study, 3D reconstructions were performed in dedicated workstations located separately from the emergency radiology CT interpretation area. During the last 7 months of the study, reconstructions were performed online by the attending radiologist or resident on duty, using a software package directly incorporated into the PACS workstations. The mean monthly number of 3D reconstructions requested during the two time periods was compared using Student's t test. The monthly mean +/- SD of 3D reconstructions performed before and after 3D software incorporation into the PACS was 34+/-7 (95% CI, 10-58) and 132+/-31 (95% CI, 111-153), respectively. This difference was statistically significant (p<0.0001). In the multiple trauma patient, implementation of PACS-integrated software increases utilization of 3D reconstructions of MDCT data sets.