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In Fig. 1c of this Article, the x-axis scale was inadvertently duplicated from Fig. 1b. The original Article has been corrected online.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

Aims: Patient-reported outcomes measures (PROMs) are an increasingly recognised end point of radiotherapy studies. We hypothesised that the baseline PROMs score is the strongest predictor for acute and late scores after treatment. We assessed the strength of association of baseline MD Anderson Symptom Inventory (MDASI) scores, alongside other known factors for patient- or clinician-reported toxicity, with acute (6-week) and late (12-month) scores in head and neck cancer (HNC) patients following (chemo)radiotherapy., Materials and Methods: This was a retrospective analysis of longitudinal MDASI scores for 247 patients receiving (chemo)radiotherapy for HNC via multivariable linear regression. The factors investigated were: baseline symptom score, age, sex, concurrent chemotherapy, disease stage, radiotherapy fractionation, prior definitive surgery and performance status. Patients with a baseline score >4 in any item were defined as symptomatic in that category., Results: Patients rated symptomatic for an MDASI item pre-treatment on average reported statistically (P < 0.0005) and clinically (>-1.5) significant reductions in scores 6 weeks and 12 months after (chemo)radiotherapy for all considered sub-items except taste, dryness of mouth and problems with teeth. Conversely patients asymptomatic at baseline reported a worsening of scores at both time points. Other investigated factors showed little association with changes in MDASI scores following treatment., Conclusions: Our data show that baseline MDASI scores are strongly associated with patient-reported toxicity 6 weeks and 12 months after (chemo)radiotherapy for HNC. Patients who are symptomatic at baseline can experience an early and durable benefit from treatment. This finding can inform discussions with patients before therapy and has implications for use of PROMs scores for the assessment of toxicity in randomised trials., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background: Ventricular assist devices (VADs) are increasingly being implanted in children, yet there is little literature to guide anesthetic management for these procedures., Aims: To describe the pediatric population presenting for VAD implantation and the anesthetic management these patients receive. To compare (a) children under and over 12 months of age and (b) children with and without congenital heart disease., Methods: Retrospective review of patients aged 0 to 17 years who underwent VAD implantation at a single center between 2014 and 2019., Results: Seventy-seven VADs were implanted in 68 patients (46 left VADs, 24 biventricular VADs, 6 right VADs, and 1 univentricular VAD). One procedure was abandoned. Preoperatively, 20 (26%) patients were supported with extracorporeal membrane oxygenation and 57 (73%) patients were ventilated. Intraoperative donor blood products were required in 74 (95%) cases. Postimplantation inotropic support was required in 66 (85%) cases overall and 46 (100%) patients receiving a left VAD. Infants under 12 months were more likely to require preoperative extracorporeal membrane oxygenation (42% vs 19%), have femoral venous access (54% vs 28%), receive an intraoperative vasoconstrictor (42% vs 24%), and have delayed sternal closure (63 vs 22%). Mortality was higher in patients under 12 months (25% vs 19%) and in patients with congenital heart disease (25% vs 20%)., Conclusions: Children undergoing VAD implantation require high levels of preoperative organ support, high-dose intraoperative inotropic support, and high-volume blood transfusion. Children under 12 months and those with congenital heart disease are particularly challenging for anesthesiologists and have worse overall outcomes.

Background: Drowning patients may benefit from the advanced airway management capabilities that can be provided by physician staffed helicopter emergency medical services. The aim of this study is to describe paediatric drowning patients treated by such a service examining tasking systems, initial physiology at the incident scene, survival and neurological outcome., Methods: Retrospective analysis of paediatric drowning victims over a 5- year period. Case identification system, patient age, site of drowning, presence or absence of cardiac output, first Glasgow Coma Scale (GCS) score and interventions were collected from prehospital notes, and survival and neurological outcomes from hospital and rehabilitation notes., Results: The P-HEMS direct case identification system operating in parallel with a central control system identified all severe drowning cases but 3 of 7 cases (43%) were missed when the central control system operated in isolation. All severe drowning cases (22) identified for P-HEMS response were intubated and transported directly to a paediatric specialist centre. Intubation required adjuvant anaesthesia in 10 (45%) cases. All children with GCS greater than eight on arrival of the P-HEMS survived neurologically intact. Seven of eight children with a GCS between four and seven survived without neurological impairment and all children with a GCS greater than three survived. Four of twelve asystolic children survived including one child who at 18 months post drowning is neurologically normal. All children who survived had return of spontaneous circulation prior to arrival in the emergency department., Conclusions: P-HEMS played a significant role in the management of severe paediatric drowning in this case series. Requirement for P-HEMS only interventions were high and all identified cases were transferred directly to a paediatric specialist centre. Discontinuation of the P-HEMS direct case identication system that operated during the majority of the study period resulted in deterioration in system performance with some paediatric drowning cases subsequently not identified for P-HEMS response being transported to adult hospitals.

Objectives: The aim of this study was to describe the mechanism and severity of injuries in the paediatric population treated by an Australian helicopter emergency medical service and to examine the frequency and nature of interventions performed. This information is important for planning education and continuing professional development in prehospital medicine., Methods: The study is a retrospective cohort analysis of 349 patients under the age of 16 treated by CareFlight in Sydney, Australia, between April 2007 and April 2012. Data collected included age, type of incident, medication and fluid administered, procedures performed, receiving hospital, 24 h and 30-day mortality and injuries sustained., Results: Falls (33%), motor vehicle incidents (30%), sport injury (14%) and immersion injury (12%) were the most common mechanisms. A total of 27 children died within 30 days; nontrauma cases were proportionally overrepresented in the deaths. With respect to tasking, 59% cases involved a severely or significantly injured child. Among the children, 97% with a traumatic mechanism were transferred directly to a paediatric trauma centre.In addition, 81% of children had at least one intervention by the helicopter emergency medical services team at the incident scene, most commonly intravenous cannulation (61%), crystalloid bolus (29%), intubation (21%) and intravenous analgesia administration (15%)., Conclusion: Paediatric prehospital patients can be of high dependency, requiring urgent critical care procedures. Training in prehospital medicine should include paediatrics. It is essential that practitioners maintain skills in venous access, airway management and provision of adequate analgesia in children.

Objective: The primary objective of this study was to describe the remote paediatric aeromedical population of the 'Top End' of the Northern Territory. The secondary objective was to identify children requiring high-dependency care by the transport team., Design: Retrospective case review., Setting: Aeromedical service in the remote Northern Territory., Participants: All patients under the age of 16 years transported over a one-year period between February 2012 and February 2013., Outcome Measures: Age, gestation if newborn, diagnosis at referral, requirement for high-dependency care and transport team members., Results: Seven hundred eighty-nine children were transported with an average age of 4.4 years (range 0 days to 16 years). Nursing staff transferred 646 (82%). Respiratory problems (bronchiolitis and pneumonia) were the predominant illness type (31%). Other frequent diagnoses were trauma (11%), gastroenteritis (10%), cellulitis or abscess (9%) and the sequelae of streptococcal infection (8%). Thirty preterm infants including seven below 31 weeks gestation were transferred. Twenty-five children required high-dependency care, 15 of these on day 0 of life. Twenty-five required respiratory support, seven central venous access, four surfactant, two inotropes and one chest tubes., Conclusions: The majority of paediatric aeromedical patients have an infective cause for their illness. Respiratory disease is the most common indication for aeromedical transport. The majority of patients are transferred by a flight nurse and do not require high-dependency care. The main risk factor identified for requiring high-dependency care during transport is respiratory distress in a newborn infant., (© 2014 National Rural Health Alliance Inc.)

Introduction: Women in labor or with complications of pregnancy in the remote, outback region of Australia's Northern Territory are transported to the hospital by air. The objective of this study was to describe the interventions required by obstetric and newborn patients during air medical transport and to evaluate how often these were beyond the scope of practice of a team consisting of an experienced midwife with or without a general flight doctor., Methods: A retrospective cohort analysis of 200 consecutive women between 20 weeks gestation up to 24 hours postpartum and newborns transferred during the same time period., Results: Only 1 obstetric patient required intervention beyond the scope of a midwife. Forty-eight newborn infants were transferred. Eleven (23%) required interventions within the skill range of a general flight doctor. Twenty (42%) required neonatal specialist care. Ten of 31 newborns requiring more than midwifery care were referred for transport while in utero., Conclusions: In this specific cohort, a midwife provided an appropriate level of maternal care to the majority of patients. Newborns frequently required clinical expertise beyond the practice scope of a midwife and general flight doctor. Most women in labor do not deliver during transport. The transport service has finite economic resources and logistical constraints. This study highlighted an ongoing challenge regarding when to request additional neonatal specialist care for preterm or high-risk patients referred for transport in utero., (Copyright © 2013 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

The shocked neonate often causes anxiety in the ED. This article aims to provide a systematic, practical approach to recognition and initial management of these patients. Their resuscitation should follow a pattern of provision of oxygen, fluid resuscitation, blood glucose correction, inotropic support and ventilation. Practical tips for intravenous access and the rationale behind choice of inotrope and anaesthetic induction agent are discussed. The major underlying causes - sepsis, cardiac disease, metabolic disease and non-accidental injury - along with their investigation and management are considered., (© 2012 The Author. EMA © 2012 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

The aims of this study were to assess changes in quality of life (QoL) scores in relation to radical radiotherapy for gynaecological cancer (before and after treatment up to 3 years), and to identify the effect that late treatment effects have on QoL. This was a prospective study involving 225 gynaecological cancer patients. A QoL instrument (European Organisation for the Research and Treatment of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal Tissues - Subjective Objective Management Analysis) were completed before and after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months after treatment). Most patients had acute physical symptoms and impaired functioning immediately after treatment. Levels of fatigue and diarrhoea only returned to those at pre-treatment assessment after 6 weeks. Patients with high treatment toxicity scores had lower global QoL scores. In conclusion, treatment with radiotherapy for gynaecological cancer has a negative effect on QoL, most apparent immediately after treatment. Certain late treatment effects have a negative effect on QoL for at least 2 years after radiotherapy. These treatment effects are centred on symptoms relating to the rectum and bowel, for example, diarrhoea, tenesmus and urgency. Future research will identify specific symptoms resulting from late treatment toxicity that have the greatest effect on QoL; therefore allowing effective management plans to be developed to reduce these symptoms and improve QoL in gynaecological cancer patients.

The tomato Cf-9 gene confers resistance to races of the leaf mould fungus Cladosporium fulvum that carry the Avr9 avirulence gene. Cf-9 was isolated by transposon tagging using a modified maize Dissociation (Ds) element. This generated an allelic series of Ds-induced mutations of Cf-9, of which two were found to confer novel phenotypes in a screen for mutants affecting wild-type Cf-9 function in trans. Genetic and molecular analysis of these mutants suggested semidominant, Avr9-dependent, negative-interfering mutations involving Ds insertions in a defined subregion of Cf-9. Interference was associated with expression of the 5'-end of Cf-9 upstream of the Ds insertions in these mutants, suggesting that truncated Cf-9 proteins were the likely cause of interference. Transgenic tomato lines harbouring Cf-9 constructs with premature stop codons in positions similar to the Ds insertions also showed interference, indicating that the presence of Ds was not required for interference to occur. Interestingly, interference in these transgenic lines was completely dominant and was associated with a pronounced developmental phenotype that was dependent on co-expression of Cf-9, Avr9 and a truncated Cf-9 transgene. However, interference with a weakly autoactive Hcr9 gene was Avr9-independent and did not cause a developmental phenotype, suggesting that localized restoration of Cf-9/Avr9-dependent cell death was responsible for the developmental phenotype. The restricted region in which truncation of Cf-9 results in dominant-negative interference suggests that leucine-rich repeats (LRR) 16-19 of Cf-9 may mediate dimerization of Cf-9 and LRRs 20-23 may mediate interactions with downstream partner proteins required for Cf-9 signalling, or vice versa.

The tomato Cf-9 gene confers resistance to races of the leaf mould fungus Cladosporium fulvum that carry the Avr9 avirulence gene. Cf-9 resides at a locus containing five paralogous genes and was isolated by transposon tagging using a modified maize Dissociation (Ds) element. The tagging experiment generated an allelic series of Ds-induced mutations of Cf-9, most of which were wild type in appearance. However, one mutant, designated M205, showed stunted growth, wilting, progressive leaf chlorosis and necrosis and constitutive expression of defence genes. The phenotype of M205 was caused by a semidominant, Avr9-independent mutation that co-segregated with a Ds element insertion at the Cf-9 locus. Molecular genetic analysis indicated that the Cf-9 locus of M205 had undergone recombination, generating a chimeric gene, designated Hcr9-M205, that comprised an in-frame fusion between the 5' coding region of the Cf-9 paralogue, Hcr9-9A, and the 3' coding region of Cf-9. The presence of a possible excision footprint adjacent to the junction between Hcr9-9A and Cf-9, and a Ds insertion at the homologous position in the downstream paralogue Hcr9-9D, is consistent with recombination between Hcr9-9A and Cf-9 promoted by transposition of Ds from Cf-9 into Hcr9-9D. Agrobacterium tumefaciens-mediated transient expression of Hcr9-M205 in Nicotiana tabacum caused chlorosis and the accumulation of defence gene transcripts, indicating that the protein encoded by this novel Hcr9 gene is autoactive.

We describe an infant with duct-dependent cardiac disease diagnosed prenatally who was born prematurely, and at extremely low weight. Treatment by infusion of prostaglandin maintained ductal patency for 66 days, permitting weight to be gained whilst under the care of a regional unit for neonatal intensive care prior to transfer for palliative cardiac surgery.

Resistance to grapevine powdery mildew is controlled by Run1, a single dominant gene present in the wild grapevine species, Muscadinia rotundifolia, but absent from the cultivated species, Vitis vinifera. Run1 has been introgressed into V. vinifera using a pseudo-backcross strategy, and genetic markers have previously been identified that are linked to the resistance locus. Here we describe the construction of comprehensive genetic and physical maps spanning the resistance locus that will enable future positional cloning of the resistance gene. Physical mapping was performed using a bacterial artificial chromosome (BAC) library constructed using genomic DNA extracted from a resistant V. vinifera individual carrying Run1 within an introgression. BAC contig assembly has enabled 20 new genetic markers to be identified that are closely linked to Run1, and the position of the resistance locus has been refined, locating the gene between the simple sequence repeat (SSR) marker, VMC4f3.1, and the BAC end sequence-derived marker, CB292.294. This region contains two multigene families of resistance gene analogues (RGA). A comparison of physical and genetic mapping data indicates that recombination is severely repressed in the vicinity of Run1, possibly due to divergent sequence contained within the introgressed fragment from M. rotundifolia that carries the Run1 gene.

Two infants underwent supra-annular placement of prosthetic mitral valves. The objective of this strategy was to insert a larger valve and delay replacement. This approach was initially successful but by two and three years later the patients developed impairment of cardiac function. The prosthesis decreased the volume and compliance of the left atrium causing high left atrial and pulmonary venous pressures. The "ventricularised" atrium below the prosthesis dilated. In neither case was it possible to delay second valve replacement.

In this study, the phenotype of psoriatic keratinocytes and fibroblasts in reconstructed skin models was compared to those constructed from normal cells. Characterization of this model by immunohistochemistry showed that classical markers of keratinocyte differentiation exhibited similar patterns of distribution in the psoriatic models to those derived from normal cells and generally reflected in vivo observations. Some crucial differences, however, were observed between normal and psoriatic models when pro-inflammatory gene expression and keratinocyte proliferation were investigated. Notably, the chemokine receptor CXCR2 was overexpressed in the psoriatic models, and, moreover, was localized to the granular layer of keratinocytes as seen in psoriasis in vivo. Pro-inflammatory genes (tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma], and interleukin 8 [IL-8]) were expressed at high levels in the psoriatic models, but were only minimally expressed in the normal models. Models derived from uninvolved psoriatic skin showed the same gene expression profile as those derived from involved skin along with an increased proliferation rate when compared to normal models. These results suggest that psoriatic individuals possess an inherent predisposition to develop the disease phenotype even in the absence of T cells. This study represents a comprehensive characterization of psoriatic human skin reconstructed in vitro, and demonstrates the potential of this model as a valuable tool in drug discovery.

Rhodamine B has been used as a histopathological stain for keratinization and cornification. Its ability as an in vitro indicator of the degree of epidermal keratinization was investigated in these preliminary studies. An immortalized human keratinocyte cell line, SVK-14, was evaluated as an alternative to primary human keratinocytes. The influence of extracellular calcium levels was evaluated alongside the effects of exposure to 1,25 (OH)(2) vitamin D(3) in serum-free and serum-containing media. Alamar blue (AB) conversion was used to measure changes in cellular reductive potential, and the amount of bound Rhodamine B relative to total protein per well was taken as an indicator of keratinization. Exposure to 1,25 (OH)(2) vitamin D(3) for 7 or 10 days did not increase Rhodamine B binding to confluent SVK-14 cultures, regardless of calcium concentration. Variation in Rhodamine B dye-binding to cells made it difficult to interpret the data. In addition, concern regarding the ability of SVK-14 cells to differentiate suggests that further studies need to be performed using normal human keratinocytes to validate this in vitro endpoint, with epidermal growth factor, insulin and hydrocortisone removed from the media to enhance epidermal differentiation.

A reproducible, quantifiable assay has been developed for the measurement of esterase activity in human keratinocyte cultures, using the model substrate 4-methyl umbelliferyl heptanoate (MUH) which is hydrolysed to the fluorescent metabolite 4-methyl umbelliferone (MU). Activity was assessed in two human keratinocyte cell lines, NCTC 2544 and SVK-14, and in freshly isolated human breast keratinocytes from primary culture to passage 3. V(max) values for MUH hydrolysing activity in the two cell lines showed that the less differentiated cell line NCTC 2544 (V(max) = 23.00 +/- 2.84) expresses a much higher activity than SVK-14s (V(max) = 13.28 +/- 1.42) which are more differentiated and able to form a cornified envelope. Activity in the freshly isolated human breast keratinocytes decreased with time in culture in all three donors tested, which is also likely to relate to the extent of cell differentiation. In human skin, xenobiotic esters penetrating the stratum corneum may be exposed to changing levels of hydrolysing esterases as they are absorbed across the epidermal cell layers. The assay for MUH hydrolysis will be a useful tool for the study of esterase activity in populations of human keratinocytes in vitro.

Twenty-four Fischer 344 rats were exposed to enriched uranium dioxide (UO2) aerosols to give a mean initial lung burden of 291 +/- 89 (SD) micrograms. Groups of rats were killed at 1, 7, 180, 360, 540, and 720 days post-inhalation (PI). Their lungs were fixed and inflated. Sections cut from all five lung lobes were used to prepare CR-39 neutron-induced 235U fission fragment autoradiographs. A single traverse across a CR-39 autoradiograph of a tissue section, from the left lung of all the rats, was made using a motorized microscopic stage. The traverse was divided into 10 fields. The track counts per field were used to test for homogeneity of track distribution and to assess if there was any tendency for tracks to be related to the peripheral region of the lung. Full raster scans across the entire tissue image were made on left lung autoradiographs from two animals killed at each time point to assess the homogeneity of fission fragment track distribution throughout the entire section. There was no evidence of any temporal change in the proportion of tracks associated with the lung periphery. At all time points PI, the track distribution was significantly nonhomogeneous, suggesting a nonuniform pattern of tissue irradiation from the 234U alpha particles. At time points from 180 to 720 days PI, large clusters of macrophages were observed in some of the sections taken from all five lung lobes. The total number of macrophage clusters increased with time PI. These macrophage clusters produced many 235U fission fragment tracks within the CR-39 autoradiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

The principal products of the photooxidation of 7,12-dimethylbenz[a]-anthracene (DMBA) in aqueous solutions by photooxidation induced by laboratory lighting have been characterized by high performance liquid chromatograms (HPLC), ultraviolet and mass spectrograms and by comparisons with authentic samples. The products identified were the 7,12-epidioxy-7,12-dihydro-7-12-dimethyl-, 7,12-dione, 7-hydroxymethyl-12-methyl-, 12-hydroxymethyl-7-methyl-, 7-formyl-12-methyl-, 12-formyl-7-methyl-, and 12-hydroxy-12-methyl-7-one derivatives of benz[a]-anthracene. The HPLC profile of products is similar to that obtained from oxidation of DMBA by 'one-electron' reagents, singlet oxygen, or liver microsomal metabolism. The first points of attack are the 7- and 12- positions. The mechanism of photooxidation appears to be generation of singlet oxygen by photodynamic effect of DMBA. None of the products is photosensitizing, however.