The nutritional management of patients with a short small intestine

The work for this thesis has been inspired by the experience gained from managing patients with inflammatory bowel disease in a specialist centre. An increasing number of patients with Crohn's disease are now surviving repeated intestinal resections which result in a short residual intestine. These patients, and others who have undergone extensive bowel resection secondary to mesenteric vascular disease, neoplasia, or radiation damage may develop a variety of nutritional deficiencies. Those least affected have a tendency to water and sodium depletion requiring oral or parenteral replacement while being able to nourish themselves satisfactorily in the normal way. In the most extreme cases, insufficient bowel remains for satisfactory nutritional function, and parenteral nutrition in the patient's home is necessary to sustain life. This thesis describes the clinical and pathophysiological features of the short bowel syndrome, and reviews the current state of knowledge regarding the use of fluid and electrolyte replacement and dietary manipulation in the management of such patients. The use of supplementary liquid diets and the techniques and problems of home enteral and parenteral nutrition are discussed. Experimental work has been undertaken with a group of patients who suffered from varying disabilities due to a short small intestine. The problems of fluid and electrolyte balance have been studied by comparing the efficiency of different sugar-electrolyte mixtures in improving sodium and water balance. This work was performed in collaboration with Dr C R Newton at St Mark's Hospital. In a series of dietary studies, a whole protein liquid diet has been compared with a chemically defined diet, and with solid food by measuring nitrogen, fat and calorie balances. The effects of varying the fat and fibre content of normal diets upon these parameters, and upon sodium, potassium, calcium and magnesium balance have been investigated. During the investigation and treatment of these patients, techniques for enteral and parenteral nutrition in the home have been developed and refined. These techniques and their complications are described and the results of therapy on patients' medical and social state presented. In the final discussion, the experimental results are drawn together and their relevance to clinical practice is discussed. Guidelines for the oral, enteral and parenteral electrolyte and nutritional support of patients with the short bowel syndrome are suggested. The appendix to the thesis contains case histories of those patients who took part in the studies of electrolyte mixtures, solid diets, and liquid supplements given orally and by nasogastric tube

Evolving the Face of a Criminal: How to Search a Face Space More Effectively

Witnesses and victims of serious crime are often required to construct a facial composite, a visual likeness of a suspect’s face. The traditional method is for them to select individual facial features to build a face, but often these images are of poor quality. We have developed a new method whereby witnesses repeatedly select instances from an array of complete faces and a composite is evolved over time by searching a face model built using PCA. While past research suggests that the new approach is superior, performance is far from ideal. In the current research, face models are built which match a witness’s description of a target. It is found that such ‘tailored’ models promote better quality composites, presumably due to a more effective search, and also that smaller models may be even better. The work has implications for researchers who are using statistical modelling techniques for recognising faces

Configural and featural information in facial-composite images

Eyewitnesses are often invited to construct a facial composite, an image created of the person they saw commit a crime that is used by law enforcement to locate criminal suspects. In the current paper, the effectiveness of composite images was investigated from traditional feature systems (E-FIT and PRO-fit), where participants (face constructors) selected individual features to build the face, and a more recent holistic system (EvoFIT), where they ‘evolved' a composite by repeatedly selecting from arrays of complete faces. Further participants attempted to name these composites when seen as an unaltered image, or when blurred, rotated, linearly stretched or converted to a photographic negative. All of the manipulations tested reduced correct naming of the composites overall except (i) for a low level of blur, for which naming improved for holistic composites but reduced for feature composites, and (ii) for 100% linear stretch, for which a substantial naming advantage was observed. Results also indicated that both featural (facial elements) and configural (feature spacing) information was useful for recognition in both types of composite system, but highly-detailed information was more accurate in the feature-based than the holistic method. The naming advantage of linear stretch was replicated using a forensically more-practical procedure with observers viewing an unaltered ¬composite sideways. The work is valuable to police practitioners and designers of facial-composite systems

Understanding the multiframe caricature advantage for recognizing facial composites.

Eyewitnesses often construct a ‘composite’ face of a person they saw commit a crime, a picture that police use to identify suspects. We described a technique (Frowd et al., 2007, Visual Cognition, 15, 1-31) based on facial caricature to facilitate recognition of these images: correct naming substantially improves when composites are seen with progressive positive caricature, where distinctive information is enhanced, and then with progressive negative caricature, the opposite. Over the course of four experiments, the underpinnings of this mechanism are explored. Positive-caricature levels were found to be largely responsible for improving naming of composites, with some benefit from negative-caricature levels. Also, different frame-presentation orders (forward, reverse, random, repeated) facilitated equivalent naming benefit relative to static composites. Overall, the data indicate that composites are usually constructed as negative caricatures

Catching more offenders with EvoFIT facial composites: Lab research and Police field trials.

Often, the only evidence of an offender’s identity comes from the memory of an eyewitness. For over 12 years, we have been developing software called EvoFIT to help eyewitnesses recover their memories of offenders’ faces, to assist police investigations. EvoFIT requires eyewitnesses to repeatedly select from arrays of faces, with ‘breeding’, to ‘evolve’ a face. Recently, police forces have been formally evaluating EvoFIT in criminal cases. The current paper describes four such police audits. It is reported that EvoFIT composites directly led to an arrest in 25.4% of cases overall; the arrest rate was 38.5% for forces that used a newer, less detailed face-recall interview. These results are similar to those found in the laboratory using simulated procedures. Here, we also evaluate the impact of interviewing techniques and outline further work that has improved system performance

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Replication of CNTNAP2 association with nonword repetition and support for FOXP2 association with timed reading and motor activities in a dyslexia family sample

Two functionally related genes, FOXP2 and CNTNAP2, influence language abilities in families with rare syndromic and common nonsyndromic forms of impaired language, respectively. We investigated whether these genes are associated with component phenotypes of dyslexia and measures of sequential motor ability. Quantitative transmission disequilibrium testing (QTDT) and linear association modeling were used to evaluate associations with measures of phonological memory (nonword repetition, NWR), expressive language (sentence repetition), reading (real word reading efficiency, RWRE; word attack, WATT), and timed sequential motor activities (rapid alternating place of articulation, RAPA; finger succession in the dominant hand, FS-D) in 188 family trios with a child with dyslexia. Consistent with a prior study of language impairment, QTDT in dyslexia showed evidence of CNTNAP2 single nucleotide polymorphism (SNP) association with NWR. For FOXP2, we provide the first evidence for SNP association with component phenotypes of dyslexia, specifically NWR and RWRE but not WATT. In addition, FOXP2 SNP associations with both RAPA and FS-D were observed. Our results confirm the role of CNTNAP2 in NWR in a dyslexia sample and motivate new questions about the effects of FOXP2 in neurodevelopmental disorders

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707