Thomas Lewis | University of Southern California (original) (raw)

Papers by Thomas Lewis

International Review of Psychiatry, Oct 22, 2019

Across the globe medical students are experiencing high levels of depression, anxiety, and psycho... more Across the globe medical students are experiencing high levels of depression, anxiety, and psychological distress. This can ultimately lead to poor academic performance, substance misuse and/or concerns over clinical practice and fitness to practice. We surveyed Jordanian medical students to assess burnout (using the Oldenburg Burnout Inventory, OLBI), minor psychiatric illness (General Health Questionnaire 12, GHQ12) and alcohol/substance abuse (CAGE questionnaire). Results indicate a high level of exhaustion (91%), disengagement (87%) and 'minor' psychiatric illness (92%). OLBI and GHQ12 scores were found to correlate positively (p < 0.001). The CAGE questionnaire was positive in 8% of students. Further research is required to confirm these results and compare them to the global burden of mental illness in medical students. Medical students in Jordan should be considered a high-risk group for burnout and mental health problems and strategies should be employed to recognise and appropriately manage those most at risk.

Canine genetics and epidemiology, Sep 21, 2015

Background: Inbreeding is inevitable in closed populations with a finite number of ancestors and ... more Background: Inbreeding is inevitable in closed populations with a finite number of ancestors and where there is selection. Therefore, management of the rate of inbreeding at sustainable levels is required to avoid the associated detrimental effects of inbreeding. Studies have shown some pedigree dog breeds to have high levels of inbreeding and a high burden of inherited disease unrelated to selection objectives, implying loss of genetic diversity may be a particular problem for pedigree dogs. Pedigree analysis of all 215 breeds currently recognised by the UK Kennel Club over the period 1980-2014 was undertaken to ascertain parameters describing the rate of loss of genetic diversity due to inbreeding, and the presence of any general trend across all breeds. Results: The trend over all breeds was for the rate of inbreeding to be highest in the 1980s and 1990s, tending to decline after 2000. The trend was comparable in very common and rarer breeds, although was more pronounced in rarer breeds. Rates of inbreeding over the entire period 1980-2014 were not correlated with census population size. The existence of popular sires was apparent in all breeds. Conclusion: The trends detected over 1980-2014 imply an initial excessive loss of genetic diversity which has latterly fallen to sustainable levels, even with modest restoration in some cases. The theory of genetic contributions, which demonstrates the fundamental relationship of inbreeding and selection, implies that popular sires are the major contributor to high rate of inbreeding.

International Review of Psychiatry, Mar 18, 2020

High levels of stress, burnout, and symptoms of poor mental health have been well known among pra... more High levels of stress, burnout, and symptoms of poor mental health have been well known among practicing doctors for a number of years. Indeed, many health systems have formal and informal mechanisms to offer support and treatment where needed, though this varies tremendously across cultures. There is increasing evidence that current medical students, our doctors of the future, also report very high levels of distress, burnout, and substance misuse. We sampled large groups of medical students in 12 countries at the same time and with exactly the same method in order to aid direct comparison. 3766 students responded to our survey across five continents in what we believe is a global first. Our results show that students in all 12 countries report very high levels of 'caseness' on validated measures of psychiatric symptoms and burnout. Rates of substance misuse, often a cause of or coping mechanism for this distress, and identified sources of stress also varied across cultures. Variations are strongly influenced by cultural factors. Further quantitative and qualitative research is required to confirm our results and further delineate the causes for high rates of psychiatric symptoms and burnout. Studies should also focus on the implementation of strategies to safeguard and identify those most at risk.

Alzheimers & Dementia, Dec 1, 2020

BackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent in Sub‐Saharan Afri... more BackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent in Sub‐Saharan Africa (SSA), due to increasing life expectancy and availability of combination antiretroviral therapy (cART). These preliminary data represent the first longitudinal study of HAND in older cART‐treated adults in SSA with the aim of reporting prevalence and persistence of cognitive impairment, and neurocognitive profile.MethodWe investigated prevalence and incidence of HAND diagnosis and subtypes (asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND) and HIV‐associated dementia (HAD), alongside neuropsychological profile and neurological symptom burden over 40 months in 253 HIV positive adults aged ≥50 attending a government clinic (2016‐2019). HAND diagnoses were reviewed annually by a consensus panel using Frascati criteria, based on detailed clinical assessment.ResultAt baseline (2016), 253 individuals underwent full assessment, of these, 185 were re‐evaluated in 2017, 181 in 2018 and 128 in 2019. 139 individuals had complete data 2016 ‐2018. The majority (68%) were female, median age at diagnosis was 51, and time since diagnosis 7.6 years. Almost all were receiving cART and were well‐managed (mn CD4 532.76. HAND prevalence was 47% in 2016 (n=253, 95.5% cART‐treated) and 49% in 2017 (one‐year incidence from those at risk 37%). Provisional follow‐up data indicates HAND prevalence of 62% in 2018 (n=172) and 54% in 2019 (n=128). Milder forms of HAND predominated, with evidence of reversibility. The predominant cognitive domains affected were both cortical and subcortical (executive function, motor speed, working memory, verbal memory (word list learning) and orientation) with visuoconstruction and language comprehension relatively spared. Both depression and neurological impairments were highly prevalent.ConclusionThis is the first longitudinal study of neurocognitive impairment in older adults living with HIV in SSA. Findings suggest cART and regular follow‐up are insufficient to prevent occurrence or progression of HAND, though the aetiology remains unclear. Both cortical and subcortical cognitive domains are affected suggesting the possibility of non‐HIV‐related neurodegenerative cognitive decline. If replicated in other SSA settings, HAND is likely to be a major cause of cognitive impairment in older people in SSA, despite cART treatment.

Journal of the Acoustical Society of America, May 1, 1998

Fish exhibit a characteristic Mauthner-initiated startle response to sudden acoustic stimuli. Thi... more Fish exhibit a characteristic Mauthner-initiated startle response to sudden acoustic stimuli. This escape response is thought to be triggered by predato~attacks since an acoustic wave is launched ahead of a striking predator. "The nature of acoustic stimuli which elicit the startle response was examined in free swimming goldfish. The results showed that a threshold level of acoustic acceleration (-30 dB re: 1 tis2), not pressure, was required to elicit a startle and that the threshold was invariant of bearing to the source. Near threshold, the fish turned in a random direction, but as the stimulus level increased, the fish was more likely to turn a~vay from the source. The lateral component of the acoustic acceleration was the relevant parameter determining directionality.

Canine genetics and epidemiology, Sep 19, 2017

Background: Pedigree or purebred dogs are often stated to have high prevalence of disorders which... more Background: Pedigree or purebred dogs are often stated to have high prevalence of disorders which are commonly assumed to be a consequence of inbreeding and selection for exaggerated features. However, few studies empirically report and rank the prevalence of disorders across breeds although such data are of critical importance in the prioritisation of multiple health concerns, and to provide a baseline against which to explore changes over time. This paper reports an owner survey that gathered disorder information on Kennel Club registered pedigree dogs, regardless of whether these disorders received veterinary care. This study aimed to determine the prevalence of disorders among pedigree dogs overall and, where possible, determine any variation among breeds. Results: This study included morbidity data on 43,005 live dogs registered with the Kennel Club. Just under two thirds of live dogs had no reported diseases/conditions. The most prevalent diseases/conditions overall were lipoma (4.3%; 95% confidence interval 4.13-4.52%), skin (cutaneous) cyst (3.1%; 2.94-3.27%) and hypersensitivity (allergic) skin disorder (2.7%; 2.52-2.82%). For the most common disorders in the most represented breeds, 90 significant differences between the within breed prevalence and the overall prevalence are reported. Conclusion: The results from this study have added vital epidemiological data on disorders in UK dogs. It is anticipated that these results will contribute to the forthcoming Breed Health & Conservation Plans, a Kennel Club initiative aiming to assist in the identification and prioritisation of breeding selection objectives for health and provide advice to breeders/ owners regarding steps that may be taken to minimise the risk of the disease/disorders. Future breed-specific studies are recommended to report more precise prevalence estimates within more breeds.

Dermatitis associated with microfilariae of a nematode of the superfamily Filarioidea was diagnos... more Dermatitis associated with microfilariae of a nematode of the superfamily Filarioidea was diagnosed in 10 dogs from the western United States. Clinically, lesions were single or multiple papules and plaques with alopecia, scarring, erythema, ulceration, or crusting. Eight dogs had lesional pruritus. Microscopically, there was perivascular, periglandular, to interstitial inflammation, with many eosinophils and/or plasma cells, and scarring affecting the dermis and subcutis. Microgranulomas containing microfilaria were seen in six dogs. Microfilariae were noted in microgranulomas or free in the dermis or subcutis, but not in vessels. In one case, an adult female nematode emerged from a biopsy sample that was placed in physiologic saline. Study of this nematode revealed that it was a filarioid of the family Onchocercidae; it was identified as Acanthocheilonema sp. (syn: Dipetalonema). Antigen tests of five dogs were negative for Dirofilaria immitis. The Knott tests and/or filter tests of nine dogs were negative for microfilariae. An indirect fluorescence antibody test of one dog was also negative for D. immitis. One dog was not evaluated for microfilariae.

Ices Journal of Marine Science, Apr 1, 1996

The gas-filled swimbladder of a fish resonates in the ambient noise field, scattering significant... more The gas-filled swimbladder of a fish resonates in the ambient noise field, scattering significant amounts of acoustic energy. The Non-invasive Vibration Amplitude Measurement System (NIVAMS) was used to measure the frequency response of the swimbladder of a freshwater species, the oscar (Astronotus ocellatus Cuvier), in a range from 200 to 2000 Hz. NIVAMS uses continuous wave ultrasound to measure swimbladder vibrational displacement amplitudes in vivo. Advantages of the NIVAMS are that it is non-invasive (no surgery is required to make the measurements) and that it is non-intrusive (the motion is unaltered by the measurement process). The response of the oscar's single-chambered swimbladder followed the general characteristics of the simple theoretical model by Andreeva (1964).

Acta Crystallographica Section E-structure Reports Online, Jun 10, 2005

Journal of the Acoustical Society of America, May 1, 1998

In order to determine the effects of low frequency underwater sound on small animal models, it is... more In order to determine the effects of low frequency underwater sound on small animal models, it is desirable to expose them to well characterized fields which closely simulates the (locally) plane wave open ocean stimulus. It is also desirable to produce pure pressure and acceleration stimuli to isolate the effects of the individual components of the acoustic p]ane wave. It is necessary to produce sufficiently strong signals to enable damage thresholds to be determined. The range of frequencies over which such stimuli must be produced is quite broad since it must include the actual band of interest (100-500 W) to examine damage on the cellular and tissue level. as well as at scaled frequencies (-l-5 W) to examine the effects of organ structure. The problem is subtler than one might imagine because of the high compliance of the test animals due to the high compliance of the test animals due to air in their lungs. Careful consideration is required to ascertain what is required of the chamber to assure valid measurements and to determine the true effective sound pressure level.

Journal of the Acoustical Society of America, Nov 1, 1995

Chair's Introduction4:00 Invited Papers 8:05 4aAB1. The physiology and psychophysics of the acous... more Chair's Introduction4:00 Invited Papers 8:05 4aAB1. The physiology and psychophysics of the acoustic startle reaction. James R. Ison (Dept. of Brain and Cognitive Sci.,

Acta Crystallographica Section E-structure Reports Online, Mar 18, 2005

Journal of the Acoustical Society of America, Apr 1, 1992

This panel discussion will highlight some of the acoustic and physiologic principles involved in ... more This panel discussion will highlight some of the acoustic and physiologic principles involved in traditional and nontraditional styles of singing. The discussion will follow a live demonstration and will include the audience.

PubMed, May 1, 1996

To assess the efficacy of emergency thoracotomy performed for thoracic trauma in the accident and... more To assess the efficacy of emergency thoracotomy performed for thoracic trauma in the accident and emergency department, a retrospective analysis of patients who underwent this procedure and were brought to hospital by the Helicopter Emergency Medical Service was carried out. Between 1991 and 1994, 16 patients had emergency thoracotomy performed in the accident department. Twelve patients had sustained blunt trauma and four patients had sustained penetrating injuries. Three patients first assessed at the scene and 11 patients on arrival at the emergency department had Glasgow Coma Scores < 3. Eight thoracotomies were performed by the cardiothoracic team and eight by the trauma team. There was one survivor in this group; he had been stabbed at multiple sites and emergency thoracotomy was required to control bleeding from an intercostal vessel. Our results demonstrate experience of one of the first phase Level One trauma centres in the United Kingdom. From our small series, we believe that selection criteria for emergency thoracotomy in trauma patients need to be revised. From this series and a review of the literature, patients with penetrating injuries, vital signs at the scene and those with a high index of suspicion for tamponade seem to benefit most from thoracotomy in the emergency setting.

Veterinary Dermatology, Jul 10, 2016

Background-Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Cocc... more Background-Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Coccidioides immitis or C. posadasii. Primary pulmonary infection can disseminate to cutaneous and subcutaneous tissues, or less commonly direct cutaneous inoculation may occur. Hypothesis/Objectives-To characterize the historical, clinical, diagnostic and treatment findings in dogs and cats with cutaneous manifestation of coccidioidomycosis. Animals-Twenty three dogs and seventeen cats diagnosed between 2009 and 2015 in Arizona, USA. Methods-Retrospective review of medical records from dogs and cats from an endemic area with a confirmed diagnosis via histopathology, cytology and/or culture, and skin lesions. Results-Age of affected dogs ranged from 14 weeks to 13 years (median = 7 years), whereas cats ranged from 3 to 17 years (median = 9 years). Subcutaneous nodules were the most common lesions in both species. Lesions were distributed widely and not often found over sites of bone infection. In 75% of dogs and 54.5% of cats with cutaneous lesions there were clinical signs of systemic illness, supporting the diagnosis of cutaneous disseminated disease. Four dogs and four cats had localized lesions with no systemic illness, consistent with possible primary cutaneous infection. The most common mode of diagnosis was cytology identification in both species. Fluconazole was the most commonly prescribed antifungal drug. Conclusions and clinical importance-Coccidioidomycosis is the most common mycosis of dogs and cats in endemic regions and cutaneous signs of the disease may be an initial presenting complaint. This study identified a variety of cutaneous manifestations of the disease in dogs and cats and should be recognized by clinicians.

bioRxiv (Cold Spring Harbor Laboratory), May 28, 2020

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and dele... more The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

PubMed, Nov 1, 1993

Background: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may ... more Background: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may be effective in the treatment of depression and that some patients, particularly those with panic disorder, may be intolerant of the 20 mg/day dose. We examined the utility of starting fluoxetine at a low daily dose (5 mg) and increasing to the standard daily dose (20 mg) in depressed outpatients with and without concurrent panic disorder. Method: One hundred thirty-three consecutive outpatients meeting DSM-III-R criteria for major depression were studied. Patients were started on fluoxetine 5 mg/day and were gradually increased to 20 mg/day over a 1-week period. Patients who were unable to reach the 20 mg/day dose were instructed to take the highest tolerable dose for the duration of the study. After a month of fluoxetine treatment, patients were evaluated for compliance with treatment and improvement on the Clinical Global Improvement scale. Results: Twenty-eight percent of the patients were unable to increase the dose to the full 20 mg. Of these patients, half could not tolerate doses lower than 20 mg and discontinued the drug, while the other half did well clinically on the lower doses. Patients who discontinued fluoxetine tended to have panic disorder in addition to depression. Conclusion: We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses. This dosing strategy may be of particular benefit for patients with panic disorder.

Crystal Growth & Design, Mar 19, 2004

An experimental study of barbituric acid found a new P2 1 /c polymorph with two conformations of ... more An experimental study of barbituric acid found a new P2 1 /c polymorph with two conformations of barbituric acid in the asymmetric unit, one molecule adopting an envelope conformation and the other refining as planar. The new Form ii involves different hydrogen bond acceptors to Form i. An ab initio conformational analysis study found that barbituric acid can change its envelope conformation by over 20°from planar with a small energy change that can be compensated for by packing forces, so that the new Form ii is predicted to have a lower lattice energy than Form i. A computational search for minima in the lattice energy found many hypothetical structures of barbituric acid within the energy range of possible polymorphism, with a variety of hydrogen bonding acceptors and motifs. The search was found to be very sensitive to the assumed molecular structure of barbituric acid, so further plausible low energy variations in the molecular conformation would produce even more low energy crystal structures. Thus, the combined experimental and theoretical studies show that barbituric acid can pack in such a variety of low energy structures that further polymorphs seem possible.

International Review of Psychiatry, Oct 22, 2019

Across the globe medical students are experiencing high levels of depression, anxiety, and psycho... more Across the globe medical students are experiencing high levels of depression, anxiety, and psychological distress. This can ultimately lead to poor academic performance, substance misuse and/or concerns over clinical practice and fitness to practice. We surveyed Jordanian medical students to assess burnout (using the Oldenburg Burnout Inventory, OLBI), minor psychiatric illness (General Health Questionnaire 12, GHQ12) and alcohol/substance abuse (CAGE questionnaire). Results indicate a high level of exhaustion (91%), disengagement (87%) and 'minor' psychiatric illness (92%). OLBI and GHQ12 scores were found to correlate positively (p < 0.001). The CAGE questionnaire was positive in 8% of students. Further research is required to confirm these results and compare them to the global burden of mental illness in medical students. Medical students in Jordan should be considered a high-risk group for burnout and mental health problems and strategies should be employed to recognise and appropriately manage those most at risk.

Canine genetics and epidemiology, Sep 21, 2015

Background: Inbreeding is inevitable in closed populations with a finite number of ancestors and ... more Background: Inbreeding is inevitable in closed populations with a finite number of ancestors and where there is selection. Therefore, management of the rate of inbreeding at sustainable levels is required to avoid the associated detrimental effects of inbreeding. Studies have shown some pedigree dog breeds to have high levels of inbreeding and a high burden of inherited disease unrelated to selection objectives, implying loss of genetic diversity may be a particular problem for pedigree dogs. Pedigree analysis of all 215 breeds currently recognised by the UK Kennel Club over the period 1980-2014 was undertaken to ascertain parameters describing the rate of loss of genetic diversity due to inbreeding, and the presence of any general trend across all breeds. Results: The trend over all breeds was for the rate of inbreeding to be highest in the 1980s and 1990s, tending to decline after 2000. The trend was comparable in very common and rarer breeds, although was more pronounced in rarer breeds. Rates of inbreeding over the entire period 1980-2014 were not correlated with census population size. The existence of popular sires was apparent in all breeds. Conclusion: The trends detected over 1980-2014 imply an initial excessive loss of genetic diversity which has latterly fallen to sustainable levels, even with modest restoration in some cases. The theory of genetic contributions, which demonstrates the fundamental relationship of inbreeding and selection, implies that popular sires are the major contributor to high rate of inbreeding.

International Review of Psychiatry, Mar 18, 2020

High levels of stress, burnout, and symptoms of poor mental health have been well known among pra... more High levels of stress, burnout, and symptoms of poor mental health have been well known among practicing doctors for a number of years. Indeed, many health systems have formal and informal mechanisms to offer support and treatment where needed, though this varies tremendously across cultures. There is increasing evidence that current medical students, our doctors of the future, also report very high levels of distress, burnout, and substance misuse. We sampled large groups of medical students in 12 countries at the same time and with exactly the same method in order to aid direct comparison. 3766 students responded to our survey across five continents in what we believe is a global first. Our results show that students in all 12 countries report very high levels of 'caseness' on validated measures of psychiatric symptoms and burnout. Rates of substance misuse, often a cause of or coping mechanism for this distress, and identified sources of stress also varied across cultures. Variations are strongly influenced by cultural factors. Further quantitative and qualitative research is required to confirm our results and further delineate the causes for high rates of psychiatric symptoms and burnout. Studies should also focus on the implementation of strategies to safeguard and identify those most at risk.

Alzheimers & Dementia, Dec 1, 2020

BackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent in Sub‐Saharan Afri... more BackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent in Sub‐Saharan Africa (SSA), due to increasing life expectancy and availability of combination antiretroviral therapy (cART). These preliminary data represent the first longitudinal study of HAND in older cART‐treated adults in SSA with the aim of reporting prevalence and persistence of cognitive impairment, and neurocognitive profile.MethodWe investigated prevalence and incidence of HAND diagnosis and subtypes (asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND) and HIV‐associated dementia (HAD), alongside neuropsychological profile and neurological symptom burden over 40 months in 253 HIV positive adults aged ≥50 attending a government clinic (2016‐2019). HAND diagnoses were reviewed annually by a consensus panel using Frascati criteria, based on detailed clinical assessment.ResultAt baseline (2016), 253 individuals underwent full assessment, of these, 185 were re‐evaluated in 2017, 181 in 2018 and 128 in 2019. 139 individuals had complete data 2016 ‐2018. The majority (68%) were female, median age at diagnosis was 51, and time since diagnosis 7.6 years. Almost all were receiving cART and were well‐managed (mn CD4 532.76. HAND prevalence was 47% in 2016 (n=253, 95.5% cART‐treated) and 49% in 2017 (one‐year incidence from those at risk 37%). Provisional follow‐up data indicates HAND prevalence of 62% in 2018 (n=172) and 54% in 2019 (n=128). Milder forms of HAND predominated, with evidence of reversibility. The predominant cognitive domains affected were both cortical and subcortical (executive function, motor speed, working memory, verbal memory (word list learning) and orientation) with visuoconstruction and language comprehension relatively spared. Both depression and neurological impairments were highly prevalent.ConclusionThis is the first longitudinal study of neurocognitive impairment in older adults living with HIV in SSA. Findings suggest cART and regular follow‐up are insufficient to prevent occurrence or progression of HAND, though the aetiology remains unclear. Both cortical and subcortical cognitive domains are affected suggesting the possibility of non‐HIV‐related neurodegenerative cognitive decline. If replicated in other SSA settings, HAND is likely to be a major cause of cognitive impairment in older people in SSA, despite cART treatment.

Journal of the Acoustical Society of America, May 1, 1998

Fish exhibit a characteristic Mauthner-initiated startle response to sudden acoustic stimuli. Thi... more Fish exhibit a characteristic Mauthner-initiated startle response to sudden acoustic stimuli. This escape response is thought to be triggered by predato~attacks since an acoustic wave is launched ahead of a striking predator. "The nature of acoustic stimuli which elicit the startle response was examined in free swimming goldfish. The results showed that a threshold level of acoustic acceleration (-30 dB re: 1 tis2), not pressure, was required to elicit a startle and that the threshold was invariant of bearing to the source. Near threshold, the fish turned in a random direction, but as the stimulus level increased, the fish was more likely to turn a~vay from the source. The lateral component of the acoustic acceleration was the relevant parameter determining directionality.

Canine genetics and epidemiology, Sep 19, 2017

Background: Pedigree or purebred dogs are often stated to have high prevalence of disorders which... more Background: Pedigree or purebred dogs are often stated to have high prevalence of disorders which are commonly assumed to be a consequence of inbreeding and selection for exaggerated features. However, few studies empirically report and rank the prevalence of disorders across breeds although such data are of critical importance in the prioritisation of multiple health concerns, and to provide a baseline against which to explore changes over time. This paper reports an owner survey that gathered disorder information on Kennel Club registered pedigree dogs, regardless of whether these disorders received veterinary care. This study aimed to determine the prevalence of disorders among pedigree dogs overall and, where possible, determine any variation among breeds. Results: This study included morbidity data on 43,005 live dogs registered with the Kennel Club. Just under two thirds of live dogs had no reported diseases/conditions. The most prevalent diseases/conditions overall were lipoma (4.3%; 95% confidence interval 4.13-4.52%), skin (cutaneous) cyst (3.1%; 2.94-3.27%) and hypersensitivity (allergic) skin disorder (2.7%; 2.52-2.82%). For the most common disorders in the most represented breeds, 90 significant differences between the within breed prevalence and the overall prevalence are reported. Conclusion: The results from this study have added vital epidemiological data on disorders in UK dogs. It is anticipated that these results will contribute to the forthcoming Breed Health & Conservation Plans, a Kennel Club initiative aiming to assist in the identification and prioritisation of breeding selection objectives for health and provide advice to breeders/ owners regarding steps that may be taken to minimise the risk of the disease/disorders. Future breed-specific studies are recommended to report more precise prevalence estimates within more breeds.

Dermatitis associated with microfilariae of a nematode of the superfamily Filarioidea was diagnos... more Dermatitis associated with microfilariae of a nematode of the superfamily Filarioidea was diagnosed in 10 dogs from the western United States. Clinically, lesions were single or multiple papules and plaques with alopecia, scarring, erythema, ulceration, or crusting. Eight dogs had lesional pruritus. Microscopically, there was perivascular, periglandular, to interstitial inflammation, with many eosinophils and/or plasma cells, and scarring affecting the dermis and subcutis. Microgranulomas containing microfilaria were seen in six dogs. Microfilariae were noted in microgranulomas or free in the dermis or subcutis, but not in vessels. In one case, an adult female nematode emerged from a biopsy sample that was placed in physiologic saline. Study of this nematode revealed that it was a filarioid of the family Onchocercidae; it was identified as Acanthocheilonema sp. (syn: Dipetalonema). Antigen tests of five dogs were negative for Dirofilaria immitis. The Knott tests and/or filter tests of nine dogs were negative for microfilariae. An indirect fluorescence antibody test of one dog was also negative for D. immitis. One dog was not evaluated for microfilariae.

Ices Journal of Marine Science, Apr 1, 1996

The gas-filled swimbladder of a fish resonates in the ambient noise field, scattering significant... more The gas-filled swimbladder of a fish resonates in the ambient noise field, scattering significant amounts of acoustic energy. The Non-invasive Vibration Amplitude Measurement System (NIVAMS) was used to measure the frequency response of the swimbladder of a freshwater species, the oscar (Astronotus ocellatus Cuvier), in a range from 200 to 2000 Hz. NIVAMS uses continuous wave ultrasound to measure swimbladder vibrational displacement amplitudes in vivo. Advantages of the NIVAMS are that it is non-invasive (no surgery is required to make the measurements) and that it is non-intrusive (the motion is unaltered by the measurement process). The response of the oscar's single-chambered swimbladder followed the general characteristics of the simple theoretical model by Andreeva (1964).

Acta Crystallographica Section E-structure Reports Online, Jun 10, 2005

Journal of the Acoustical Society of America, May 1, 1998

In order to determine the effects of low frequency underwater sound on small animal models, it is... more In order to determine the effects of low frequency underwater sound on small animal models, it is desirable to expose them to well characterized fields which closely simulates the (locally) plane wave open ocean stimulus. It is also desirable to produce pure pressure and acceleration stimuli to isolate the effects of the individual components of the acoustic p]ane wave. It is necessary to produce sufficiently strong signals to enable damage thresholds to be determined. The range of frequencies over which such stimuli must be produced is quite broad since it must include the actual band of interest (100-500 W) to examine damage on the cellular and tissue level. as well as at scaled frequencies (-l-5 W) to examine the effects of organ structure. The problem is subtler than one might imagine because of the high compliance of the test animals due to the high compliance of the test animals due to air in their lungs. Careful consideration is required to ascertain what is required of the chamber to assure valid measurements and to determine the true effective sound pressure level.

Journal of the Acoustical Society of America, Nov 1, 1995

Chair's Introduction4:00 Invited Papers 8:05 4aAB1. The physiology and psychophysics of the acous... more Chair's Introduction4:00 Invited Papers 8:05 4aAB1. The physiology and psychophysics of the acoustic startle reaction. James R. Ison (Dept. of Brain and Cognitive Sci.,

Acta Crystallographica Section E-structure Reports Online, Mar 18, 2005

Journal of the Acoustical Society of America, Apr 1, 1992

This panel discussion will highlight some of the acoustic and physiologic principles involved in ... more This panel discussion will highlight some of the acoustic and physiologic principles involved in traditional and nontraditional styles of singing. The discussion will follow a live demonstration and will include the audience.

PubMed, May 1, 1996

To assess the efficacy of emergency thoracotomy performed for thoracic trauma in the accident and... more To assess the efficacy of emergency thoracotomy performed for thoracic trauma in the accident and emergency department, a retrospective analysis of patients who underwent this procedure and were brought to hospital by the Helicopter Emergency Medical Service was carried out. Between 1991 and 1994, 16 patients had emergency thoracotomy performed in the accident department. Twelve patients had sustained blunt trauma and four patients had sustained penetrating injuries. Three patients first assessed at the scene and 11 patients on arrival at the emergency department had Glasgow Coma Scores < 3. Eight thoracotomies were performed by the cardiothoracic team and eight by the trauma team. There was one survivor in this group; he had been stabbed at multiple sites and emergency thoracotomy was required to control bleeding from an intercostal vessel. Our results demonstrate experience of one of the first phase Level One trauma centres in the United Kingdom. From our small series, we believe that selection criteria for emergency thoracotomy in trauma patients need to be revised. From this series and a review of the literature, patients with penetrating injuries, vital signs at the scene and those with a high index of suspicion for tamponade seem to benefit most from thoracotomy in the emergency setting.

Veterinary Dermatology, Jul 10, 2016

Background-Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Cocc... more Background-Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Coccidioides immitis or C. posadasii. Primary pulmonary infection can disseminate to cutaneous and subcutaneous tissues, or less commonly direct cutaneous inoculation may occur. Hypothesis/Objectives-To characterize the historical, clinical, diagnostic and treatment findings in dogs and cats with cutaneous manifestation of coccidioidomycosis. Animals-Twenty three dogs and seventeen cats diagnosed between 2009 and 2015 in Arizona, USA. Methods-Retrospective review of medical records from dogs and cats from an endemic area with a confirmed diagnosis via histopathology, cytology and/or culture, and skin lesions. Results-Age of affected dogs ranged from 14 weeks to 13 years (median = 7 years), whereas cats ranged from 3 to 17 years (median = 9 years). Subcutaneous nodules were the most common lesions in both species. Lesions were distributed widely and not often found over sites of bone infection. In 75% of dogs and 54.5% of cats with cutaneous lesions there were clinical signs of systemic illness, supporting the diagnosis of cutaneous disseminated disease. Four dogs and four cats had localized lesions with no systemic illness, consistent with possible primary cutaneous infection. The most common mode of diagnosis was cytology identification in both species. Fluconazole was the most commonly prescribed antifungal drug. Conclusions and clinical importance-Coccidioidomycosis is the most common mycosis of dogs and cats in endemic regions and cutaneous signs of the disease may be an initial presenting complaint. This study identified a variety of cutaneous manifestations of the disease in dogs and cats and should be recognized by clinicians.

bioRxiv (Cold Spring Harbor Laboratory), May 28, 2020

The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and dele... more The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

PubMed, Nov 1, 1993

Background: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may ... more Background: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may be effective in the treatment of depression and that some patients, particularly those with panic disorder, may be intolerant of the 20 mg/day dose. We examined the utility of starting fluoxetine at a low daily dose (5 mg) and increasing to the standard daily dose (20 mg) in depressed outpatients with and without concurrent panic disorder. Method: One hundred thirty-three consecutive outpatients meeting DSM-III-R criteria for major depression were studied. Patients were started on fluoxetine 5 mg/day and were gradually increased to 20 mg/day over a 1-week period. Patients who were unable to reach the 20 mg/day dose were instructed to take the highest tolerable dose for the duration of the study. After a month of fluoxetine treatment, patients were evaluated for compliance with treatment and improvement on the Clinical Global Improvement scale. Results: Twenty-eight percent of the patients were unable to increase the dose to the full 20 mg. Of these patients, half could not tolerate doses lower than 20 mg and discontinued the drug, while the other half did well clinically on the lower doses. Patients who discontinued fluoxetine tended to have panic disorder in addition to depression. Conclusion: We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses. This dosing strategy may be of particular benefit for patients with panic disorder.

Crystal Growth & Design, Mar 19, 2004

An experimental study of barbituric acid found a new P2 1 /c polymorph with two conformations of ... more An experimental study of barbituric acid found a new P2 1 /c polymorph with two conformations of barbituric acid in the asymmetric unit, one molecule adopting an envelope conformation and the other refining as planar. The new Form ii involves different hydrogen bond acceptors to Form i. An ab initio conformational analysis study found that barbituric acid can change its envelope conformation by over 20°from planar with a small energy change that can be compensated for by packing forces, so that the new Form ii is predicted to have a lower lattice energy than Form i. A computational search for minima in the lattice energy found many hypothetical structures of barbituric acid within the energy range of possible polymorphism, with a variety of hydrogen bonding acceptors and motifs. The search was found to be very sensitive to the assumed molecular structure of barbituric acid, so further plausible low energy variations in the molecular conformation would produce even more low energy crystal structures. Thus, the combined experimental and theoretical studies show that barbituric acid can pack in such a variety of low energy structures that further polymorphs seem possible.