Automated particle recognition for engine soot nanoparticles.

A pre-trained convolution neural network based on residual error functions (ResNet) was applied to the classification of soot and non-soot carbon nanoparticles in TEM images. Two depths of ResNet, one 18 layers deep and the other 50 layers deep, were trained using training-validation sets of increasing size (containing 100, 400 and 1400 images) and were assessed using an independent test set of 200 images. Network training was optimised in terms of mini-batch size, learning rate and training length. In all tests, ResNet18 and ResNet50 had statistically similar performances, though ResNet18 required only 25-35% of the training time of ResNet50. Training using the 100-, 400- and 1400-image training-validation sets led to classification accuracies of 84%, 88% and 95%, respectively. ResNet18 and ResNet50 were also compared for their ability to categorise soot and non-soot nanoparticles via a fivefold cross-validation experiment using the entire set of 800 images of soot and 800 images of non-soot. Cross-validation was repeated 3 times with different training durations. For all cross-validation experiments, classification accuracy exceeded 91%, with no statistical differences between any of the network trainings. The most efficient network was ResNet18 trained for 5 epochs, which reached 91.2% classification after only 84 s of training on 1600 images. Use of ResNet for classification of 1000 images, the amount suggested for reliable characterisation of soot sample, requires <4 s, compared with >30 min for a skilled operator classifying images manually. Use of convolution neural networks for classification of soot and non-soot nanoparticles in TEM images is highly promising, particularly when manually classified data sets have already been established.

A core outcome set for pre-eclampsia research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for pre-eclampsia. DESIGN: Consensus development study. SETTING: International. POPULATION: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. METHODS: Modified Delphi method and Modified Nominal Group Technique. RESULTS: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. CONCLUSIONS: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. TWEETABLE ABSTRACT: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].

Major obstetric haemorrhage of 2000 ml or greater: a clinical audit.

Haemorrhage remains a leading cause of maternal death. We conducted an audit to identify strategies to improve the management at our local NHS Trust. A data collection form was based on our local guideline. A coded database search was conducted for all deliveries where the estimated blood loss was ≥2000 ml (from June 1 2015 to December 31 2015), returning 68 search results (13.7/1000 births). Fifty-six records were included. Poor compliance (<75%) was seen in some key areas including the major obstetric haemorrhage (MOH) call activation (52%), the presence of an anaesthetic consultant (63%) and tranexamic acid administration (46%). Thirty out of 56 cases (54%) were acutely transfused. Women, who were not transfused acutely, appeared to be more likely to need a secondary transfusion if no MOH call had been activated (9/27 (33%) versus 3/29 (10%), p = .052). A key area for improvement was the activation of MOH calls. Following this audit, we adjusted our guideline to make it more clinically useful and staff training sessions were held, including simulation training. Impact statement What is already known on this subject? A postpartum haemorrhage (PPH) is an obstetric emergency. A structured approach is important to optimise the care of the mothers during this dangerous time, and has been shown to reduce the transfusion requirements. However, clinical practice may not adhere to the guideline recommendations. What the results of this study add? With the objective evidence of increased rates of PPH ≥2000 ml at our institution, our work identifying the flaws in management was a critical component of the work to improve the outcomes. This study gives impetus to find innovative ways to improve adherence to guidelines, and inspired an update of our local guideline to improve the applicability and utility. This project suggests a new marker for the adequacy of an acute management (a requirement for secondary blood transfusion without having received an acute transfusion), and raises questions about what constitutes optimum PPH management. What the implications are of these findings for clinical practice and/or further research? The primary and secondary transfusion data raised new questions to investigate in the future: does the involvement of consultants and the escalation of care via the instigation of major haemorrhage protocols improve decision-making and patient outcomes? Does the necessity for a secondary transfusion indicate a suboptimal acute care?

A matched comparison study of hepatitis C treatment outcomes in the prison and community setting, and an analysis of the impact of prison release or transfer during therapy.

Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.

BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer.

BACKGROUND: Current knowledge of the aetiology of hereditary breast cancer in the four main South African population groups (black, coloured, Indian and white) is limited. Risk assessments in the black, coloured and Indian population groups are challenging because of restricted information regarding the underlying genetic contributions to inherited breast cancer in these populations. We focused this study on premenopausal patients (diagnosed with breast cancer before the age of 50; n = 78) and triple negative breast cancer (TNBC) patients (n = 30) from the four South African ethnic groups. The aim of this study was to determine the frequency and spectrum of germline mutations in BRCA1, BRCA2 and PALB2 and to evaluate the presence of the CHEK2 c.1100delC allele in these patients. METHODS: In total, 108 South African breast cancer patients underwent mutation screening using a Next-Generation Sequencing (NGS) approach in combination with Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large rearrangements in BRCA1 and BRCA2. RESULTS: In 13 (12 %) patients a deleterious mutation in BRCA1/2 was detected, three of which were novel mutations in black patients. None of the study participants was found to have an unequivocal pathogenic mutation in PALB2. Two (white) patients tested positive for the CHEK2 c.1100delC mutation, however, one of these also carried a deleterious BRCA2 mutation. Additionally, six variants of unknown clinical significance were identified (4 in BRCA2, 2 in PALB2), all in black patients. Within the group of TNBC patients, a higher mutation frequency was obtained (23.3 %; 7/30) than in the group of patients diagnosed before the age of 50 (7.7 %; 6/78). CONCLUSION: This study highlights the importance of evaluating germline mutations in major breast cancer genes in all of the South African population groups. This NGS study shows that mutation analysis is warranted in South African patients with triple negative and/or in premenopausal breast cancer.

Does rheumatoid arthritis disease activity correlate with weather conditions?

To determine whether rheumatoid arthritis disease activity correlates with changing weather conditions. A longitudinal analysis of 133 patients attending the Department of Rheumatology, Musgrave Park Hospital, Belfast was performed. Participants had a diagnosis of rheumatoid arthritis and were receiving subcutaneous anti-TNF therapy (Adalimumab or Etanercept) for a period of >6 months. Data were collected at five time points. This included tender joint count, swollen joint count, patient visual analogue score (VAS), erythrocyte sedimentation rate, C-reactive protein, VAS, and DAS-28 (Disease Activity Score). Each weather factor (maximum, minimum temperature, pressure, rainfall, sunshine, humidity, and wind-speed) was analysed against each patients' DAS-28 score at five time points, using an analysis of covariance. A significant correlation was noted between low DAS-28 and increased hours of sunshine (p < 0.001). Sunny conditions were associated with a DAS-28 reduction of 0.037 (95 % CI -0.059, -0.016) p < 0.001. A significant correlation between humidity and DAS-28 was also noted (p = 0.016). Increased humidity was associated with an increased DAS-28 of 0.007 (95 % CI 0.001, 0.013) p = 0.016. Higher temperatures were associated with a non-significant decrease in DAS-28 (p = 0.16). In this study, rheumatoid arthritis disease activity (as measured by DAS-28) was significantly lower in both more sunny and less humid conditions.

Impact of intrapancreatic or extrapancreatic bile duct involvement on survival following pancreatoduodenectomy for common bile duct cancer.

BACKGROUND: The clinicopathological factors that influence survival following pancreatoduodenectomy (PD) for common bile duct (CBD) cancer are not well known. This study aimed to investigate the effect of tumour involvement of the intrapancreatic versus extrapancreatic CBD on margin status, overall (OS) and disease-free (DFS) survival. METHODS: This was a retrospective study of patients who underwent PD for CBD cancer between 2001 and 2009. Pathological examination was performed according to a previously described standardized protocol based on axial slicing. Clinicopathological data and outcome in terms of margin status, DFS and OS were compared between cancers involving exclusively the intrapancreatic CBD (CBDin) and those involving the extrapancreatic CBD, in isolation or combined with invasion of the intrapancreatic part of the duct (CBDex). RESULTS: A total of 66 patients were enrolled. Most CBD cancers were locally advanced (97 per cent pathological (p) T3, 76 per cent pN1). Microscopic margin involvement (R1) was more frequent in CBDex than in CBDin cancers (34 of 39 versus 13 of 27; P = 0.001), more often multifocal (P < 0.001) and more frequently affected the periductal margin (P = 0.005). Venous resection was more often required for CBDex cancers (P = 0.009). CBDex cancers were associated with worse OS (median 21 versus 28 months; P = 0.020) and DFS (14 versus 31 months; P = 0.015), but the rate and site of recurrence did not differ. Metastasis to more than two lymph nodes was an independent predictor of OS and DFS. CONCLUSION: CBDex cancer is associated with a higher rate of R1 resection and venous resection after PD, and has a worse outcome than CBDin cancer.

The effect of a digital training tool to aid chest image interpretation: Hybridising eye tracking technology and a decision support tool.

INTRODUCTION: Eye tracking technology, checklists and search strategies have been demonstrated as useful aids in image interpretation. A training tool was developed, by the research team, which included these features. This study aimed to evaluate the effect of the training tool on participant image interpretation performance. METHODS: The study was carried out with reporting radiographers who had either commenced training in chest image interpretation (n = 12) or were trained in musculoskeletal image interpretation (n = 23) (total n = 35). Participants were allocated to a control or intervention group. Participants completed an initial assessment at recruitment and re-attended nine months later for a follow-up assessment. The intervention group were given unlimited access to a digital training tool. During assessments participants interpreted 20 chest images whilst using eye tracking technology (total of 1400 images were interpreted). A confidence level was obtained from participants on their diagnosis and a questionnaire, to obtain demographic data, was completed following the assessment. RESULTS: Improvements were seen in the confidence of intervention group participants (p < 0.05). False Positive (FP) scores decreased for both the control and intervention group (p < 0.05), this decrease was from 4.20 to 3.20 for the control group and from 5.87 to 3.27 for the intervention group. True Negative (TN) scores increased, from 5.13 to 6.73 for the intervention group (p < 0.05). Mean decision time decreased for both the control and intervention group. CONCLUSION: The tool led to positive effects on participant performance and could be a useful aid in chest image interpretation learning. IMPLICATIONS FOR PRACTICE: Improvements in performance were observed with a digital tool. The tool could improve image interpretation methods and training.

Disparities in Emergent Colectomy for Colorectal Cancer Contribute to Inequalities in Postoperative Morbidity and Mortality in The US Health Care System.

BACKGROUND AND AIMS: Colorectal cancer is the third most common cancer among both men and women in the United States. We aimed to determine racial and socioeconomic disparities in emergent colectomy rates for colorectal cancer in the US Health Care system. MATERIAL AND METHODS: We performed a retrospective analysis of the National Inpatient Sample including adult patients (⩾18 years) diagnosed with colorectal cancer, and who underwent colorectal resection while admitted between 2008 and 2015. Multivariable logistic and linear regression were used to assess the association between emergent admissions, compared to elective admissions, and postoperative outcomes. RESULTS: A total of 141,641 hospitalizations were included: 93,775 (66%) were elective admissions and 47,866 (34%) were emergent admissions. Black patients were more likely to undergo emergent colectomy, compared to white patients (42% vs 32%, p < 0.0001). Medicaid and Medicare patients were also more likely to have an emergent colectomy, compared to private insurance (47% and 36% vs 25%, respectively, p < 0.0001), as were patients with low household income, compared to highest (38% vs 31%, p < 0.0001). Emergent procedures were less likely to be laparoscopic (19% vs 38%, p < 0.0001). Patients undergoing emergent colectomy were significantly more likely to have postoperative venous thromboembolism, wound complications, infection, bleeding, cardiac failure, renal failure, respiratory failure, shock, and inpatient mortality. CONCLUSION: There are significant racial and socioeconomic disparities in emergent colectomy rates for colorectal cancer. Efforts to reduce this disparity in colorectal cancer surgery patients should be prioritized to improve outcomes.

Does fructan have a functional role in physiological traits? Investigation by quantitative trait locus mapping.

* The role of fructan in growth and drought-stress responses of perennial ryegrass (Lolium perenne) was investigated in an F(2) mapping family that segregates for carbohydrate metabolism. * A quantitative trait locus approach was used to compare the genetic control of traits. * Growth and drought-stress traits were extremely variable within the family. Most traits had high broad-sense heritability. Quantitative trait loci (QTL) were identified for most traits; the maximum number of QTL per trait was four. Between 11% and 75% of total phenotypic variation was explained. Few growth-trait QTL coincided with previously identified fructan QTL. A cluster of drought-trait QTL was close to two previously identified regions of the genome with tiller base fructan QTL in repulsion. * The high sugar parent contributed few alleles that increased 'reserve-driven' growth or performance during drought-stress. Correlation of growth and drought-stress traits with fructan content was low and increasing fructan content per se would not appear to improve drought resistance. Complex patterns of carbohydrate partitioning and metabolism within the cell may explain contradictory relationships between carbohydrate content and growth/stress-resistance traits.

Cerebrovascular dysplasia in neurofibromatosis type 1.

OBJECTIVE: To assess the frequency and clinical characteristics of the increasingly recognised complication of cerebrovascular dysplasia in children with neurofibromatosis type 1 (NF1). METHODS: A series of seven patients with NF1 and cerebrovascular dysplasias that were not secondary to radiotherapy were identified and prospectively assessed. An extensive review of the literature was also performed to identify associated features and the natural history of this potentially severe complication of NF1. RESULTS: The frequency of cerebrovascular dysplasia in NF1 was found to be 2-5%, and vascular lesions were clearly visible on routine MRI of the brain. The majority of patients were clinically asymptomatic, despite angiographic progression in some cases. Hypoplastic carotid canals and early appearance on MRI suggested that a proportion of cases of cerebrovascular dysplasia were congenital in origin. CONCLUSION: These findings have implications for screening of asymptomatic patients with NF1, and highlight the difficult management decisions in those patients identified with cerebrovascular malformations.

Digital training platform for interpreting radiographic images of the chest.

INTRODUCTION: Time delays and errors exist which lead to delays in patient care and misdiagnosis. Reporting clinicians follow guidance to form their own search strategy. However, little research has tested these training guides. With the use of eye tracking technology and expert input we developed a digital training platform to be used in chest image interpretation learning. METHODS: Two sections of a digital training platform were planned and developed; A) a search strategy training tool to assist reporters during their interpretation of images, and B) an educational tool to communicate the search strategies of expert viewers to trainees by using eye tracking technology. RESULTS: A digital training platform for use in chest image interpretation was created based on evidence within the literature, expert input and two search strategies previously used in clinical practice. Images and diagrams, aiding translation of the platform content, were incorporated where possible. The platform is structured to allow the chest image interpretation process to be clear, concise and methodical. CONCLUSION: A search strategy was incorporated within the tool to investigate its use, with the possibility that it could be recommended as an evidence based approach for use by reporting clinicians. Eye tracking, a checklist and voice recordings have been combined to form a multi-dimensional learning tool, which has never been used in chest image interpretation learning before. The training platform for use in chest image interpretation learning has been designed, created and digitised. Future work will establish the efficacy of the developed approaches.

The use of intranasal midazolam in the treatment of paediatric dental patients.

The aim of this study was to assess the use of intranasal midazolam in paediatric dental patients requiring extractions or simple surgical procedures who may otherwise have required a general anaesthetic. Twenty children aged between 2-9 years who required simple surgical procedures were given 0.25 mg.kg(-1) midazolam, administered using a MAD (Mucosal Atomization Device; Wolfe Tory Medical Inc., Salt Lake City, UT, USA). Compliance with the full dose was achieved in 14 patients, 13 of whom completed the treatment. One of two patients who allowed only partial administration completed the treatment and three patients did not comply. The mean time to starting treatment was 13 min (range 6-25 min) and patients were discharged after a mean of 46 min (range 25-67 min). Physiological parameters remained stable throughout with no clinically significant episodes of desaturation. One patient vomited at home postoperatively. Midazolam in a dose of 0.25 mg.kg(-1) administered intranasally provided adequate anxiolysis for the majority of children, allowing them to complete their treatment.

The dental practitioner and child protection in Scotland.

OBJECTIVES: To identify from general dental practitioners: undergraduate and postgraduate training experience in child protection; numbers of suspected cases of child physical abuse; reasons for failing to report suspicious cases of child physical abuse; knowledge of local child protection protocols and procedures for referral. MATERIALS AND METHODS: Postal questionnaires were sent to 500 randomly selected general dental practitioners in Scotland, with a further 200 sent to a random sample of the original 500 to increase response rate. RESULTS: Sixty-one per cent (306) of the original 500 questionnaires, and 35% (69) of the second random mail shot of 200 questionnaires were returned. Only 19% could remember any undergraduate training and 16% had been to a postgraduate lecture or seminar in child protection. Twenty-nine per cent of dentists had seen at least one suspicious case in their career. Only 8% of suspicious cases were referred on to the appropriate authorities. Reasons for failure to refer revealed that 11% were concerned about a negative impact on their practice, 34% feared family violence towards the child, 31% feared violence directed against them, and 48% feared litigation. Only 10% of dentists had been sent a copy of the local child protection guidelines on commencing work and only 15% had seen their Area Child Protection Committee (ACPC) Guidelines via any route. CONCLUSIONS: Due to lack of training or clear guidelines for dentists in Scotland, most practitioners were unsure what to do in the event of a suspicion of child abuse. Twenty-one per cent of dentists had encountered suspicious cases but failed to take any action. Dentists overwhelmingly requested appropriate training. This training should address dental competence in assessment of suspicious indicators and involve dentists in inter-agency child protection training.

Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input.

Topochemical conversion of a dense metal-organic framework from a crystalline insulator to an amorphous semiconductor.

The topochemical conversion of a dense, insulating metal-organic framework (MOF) into a semiconducting amorphous MOF is described. Treatment of single crystals of copper(i) chloride trithiocyanurate, CuICl(ttcH3) (ttcH3 = trithiocyanuric acid), 1, in aqueous ammonia solution yields monoliths of amorphous CuI1.8(ttc)0.6(ttcH3)0.4, 3. The treatment changes the transparent orange crystals of 1 into shiny black monoliths of 3 with retention of morphology, and moreover increases the electrical conductivity from insulating to semiconducting (conductivity of 3 ranges from 4.2 × 10-11 S cm-1 at 20 °C to 7.6 × 10-9 S cm-1 at 140 °C; activation energy = 0.59 eV; optical band gap = 0.6 eV). The structure and properties of the amorphous conductor are fully characterized by AC impedance spectroscopy, X-ray photoelectron spectroscopy, X-ray pair distribution function analysis, infrared spectroscopy, diffuse reflectance spectroscopy, electron spin resonance spectroscopy, elemental analysis, thermogravimetric analysis, and theoretical calculations.

Giant cell hepatitis associated with systemic lupus erythematosus.

Giant hepatocytes are commonly found in several neonatal and infantile liver diseases, but are rarely found in adult liver disease. A 42 year old white woman presented with a five month history of paraesthesia and numbness of both the upper and lower limbs and with vague abdominal pain. Abnormal liver function was noted on routine screening. Ultrasound scan of the abdomen showed gallstones; barium enema, ERCP and computed tomography scan were all normal. IgG antibodies to double stranded DNA were present at a titre of 40 units. Anti-cardiolipin antibodies, anti-mitochondrial antibodies and rheumatoid factor were not detected. Serology for hepatitis A, B, C, and paramyxoviruses was negative, as was the Paul Bunnell test. A clinical diagnosis of systemic lupus erythematosus (SLE) with an axonal sensory polyneuropathy was made, the latter confirmed on biopsy of the sural nerve. Giant cells were noted on liver biopsy. The patient was treated with corticosteroids; liver function had improved after two years of follow up. When extensive giant cell transformation is noted on liver biopsy, particularly when neuropathy is also a feature, the possibility of an association with SLE should be considered.

Histological identification of Helicobacter pylori: comparison of staining methods.

AIM: To determine whether two recently described staining methods (the modified McMullen's and the Helicobacter pylori silver stain HpSS methods) used for the histological identification of H pylori organisms are superior to two established techniques (the modified Giemsa and anti-H pylori antibody immunostain) in terms of availability, reproducibility, rapidity, sensitivity, and cost. METHODS: Histological sections from 63 paired gastric biopsies from adult patients previously investigated for dyspepsia were stained with the four methods and these were assessed blindly and independently by two observers. Of the 63 patients, 30 were originally negative in all tests for H pylori infection, 30 were positive, and the remaining three cases had discordant results using a combination of five tests (rapid biopsy urease test, urea breath test, culture, serology, and histology). RESULTS: Interobserver agreement was best with the antibody method (98%), followed by the McMullen's (90%), Giemsa (87%), and HpSS (85%). Of the 60 "gold standard" positive and negative cases, 30 were positive by the modified Giemsa stain, 29 by the McMullen's method, 29 by HpSS, and 30 by the antibody stain. However, there were two false positives with the HpSS method. The modified Giemsa is the cheapest and easiest to perform technically. CONCLUSIONS: When H pylori are present, careful examination will almost always reveal them, whichever of these stains is used. However, the modified Giemsa stain is the method of choice because it is sensitive, cheap, easy to perform, and reproducible.

Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?

BACKGROUND: An increase in intraepithelial lymphocytes (IELs) is mandatory for the histological diagnosis of coeliac disease (CD). Currently, duodenal biopsies are used almost exclusively to establish the diagnosis, yet published work continues to cite an upper limit of 40 lymphocytes/100 epithelial cells, a figure derived from jejunal biopsies over 30 years ago. AIM: To establish the normal range for IEL counts in distal duodenal biopsies. MATERIALS/METHODS: Twenty subjects (seven men, 13 women; median age, 34 years; range, 20-65) with a normal sugar permeability test and concurrent distal duodenal biopsies were identified. The number of IELs and epithelial cell nuclei in an uninterrupted length of surface (villous) epithelium (> 500 cells) was counted. An image analysis system was used to assess villous architecture by calculating the villous height to crypt depth ratio. RESULTS: The range of IEL counts in 20 subjects was 1.8-26/100 villous epithelial cells, with a mean value of 11 and SD of 6.8. The mean villous to crypt ratio was 1.82 (SD, 0.38; range, 1.22-2.46). There was no correlation between IEL counts and villous to crypt ratio (Spearman rank correlation, -0.066; p = 0.80). CONCLUSIONS: These results suggest that 25 IELs/100 epithelial cells (mean +2 SD) should be taken as the upper limit of the normal range for duodenal mucosa.

Phrenic motoneuron firing rates before, during, and after prolonged inspiratory resistive loading.

Phrenic motoneuron firing rates during brief inspiratory resistive loading (IRL) are high, and nearly all the motoneurons are recruited. Diaphragmatic fatigue has been difficult to demonstrate during IRL. Furthermore, evidence from studies in limb muscles has shown variable motoneuron responses to prolonged high-intensity loads. We studied phrenic motoneuron firing rates before, during, and after prolonged IRL in anesthetized rabbits. Of 117 phrenic axons, only 2 axons were not recruited; 41 axons were silent during unloaded breathing but were recruited at higher loads. Silent axons showed a more rapid increase in firing rate as the load increased. Phrenic motoneuron firing rates increased throughout the period of loading, whereas airway pressure swings did not. After prolonged IRL, higher motoneuron firing rates were needed during brief loads to produce the same airway pressure. No evidence of a decline in motoneuron firing rates was seen at any point. We conclude that the respiratory muscles can be shown to demonstrate physiological responses consistent with fatigue during prolonged IRL, and activation rates are high and remain so throughout this prolonged loading.