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Peter Cameron

Publications and source records attributed to Peter Cameron.

9 recordsLinked to original sources
PubMed2025

Design of highly functional genome editors by modelling CRISPR-Cas sequences.

Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology and human health. CRISPR-based gene editors derived from microorganisms, although powerful, often show notable functional tradeoffs when ported into non-native environments, such as human cells1. Artificial-intelligence-enabled design provides a powerful alternative with the potential to bypass evolutionary constraints and generate editors with optimal properties. Here, using large language models2 trained on biological diversity at scale, we demonstrate successful precision editing of the human genome with a programmable gene editor designed with artificial intelligence. To achieve this goal, we curated a dataset of more than 1 million CRISPR operons through systematic mining of 26 terabases of assembled genomes and metagenomes. We demonstrate the capacity of our models by generating 4.8× the number of protein clusters across CRISPR-Cas families found in nature and tailoring single-guide RNA sequences for Cas9-like effector proteins. Several of the generated gene editors show comparable or improved activity and specificity relative to SpCas9, the prototypical gene editing effector, while being 400 mutations away in sequence. Finally, we demonstrate that an artificial-intelligence-generated gene editor, denoted as OpenCRISPR-1, exhibits compatibility with base editing. We release OpenCRISPR-1 to facilitate broad, ethical use across research and commercial applications.

CRISPR-Cas Systems↗
PubMed2003

Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience.

PURPOSE: To report the initial experience regarding thin-section computed tomographic (CT) findings in patients with severe acute respiratory syndrome (SARS) who improved clinically after treatment. MATERIALS AND METHODS: Twenty-four patients (10 men, 14 women; mean age, 39 years; age range, 23-70 years) with confirmed SARS underwent follow-up thin-section CT of the thorax. The scans were obtained on average 36.5 days after hospital admission and were analyzed for parenchymal abnormality (ground-glass opacification, consolidation, or interstitial thickening) and evidence of fibrosis (parenchymal band, traction bronchiectasis, irregular interfaces). Patients were assigned to group 1 (with CT evidence of fibrosis) and group 2 (without CT evidence of fibrosis) for analysis. Patient demographics, length of hospital stay, rate of intensive care unit admission, peak lactate dehydrogenase level, pulsed intravenous methylprednisolone therapy, and peak opacification on chest radiographs were compared between the two groups. RESULTS: Parenchymal abnormality was found in 96% (23 of 24) of patients and ranged from residual ground-glass opacification and interstitial thickening in group 2 (nine of 24, 38%) to fibrosis in group 1 (15 of 24, 62%). Patients in group 1 were older (mean age, 45 vs 30.3 years), had a higher rate of intensive care unit admission (27% [four of 15] vs 11% [one of nine]), more requirement for pulsed intravenous methylprednisolone (87%, [13 of 15] vs 67% [six of nine]), higher peak lactate dehydrogenase level (438.9 vs 355.6 U/L), and higher peak opacification on chest radiographs (estimated area, 14% vs 11%) than patients in group 2. CONCLUSION: Pulmonary fibrosis may develop early in patients with SARS who have been discharged after treatment. Patients who are older and have more severe disease during treatment are more likely to develop thin-section CT findings of fibrosis.

Adult↗
PubMed2003

Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients.

PURPOSE: To retrospectively evaluate the radiographic appearances and pattern of progression of severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Chest radiographs obtained at clinical presentation and during treatment in 138 patients with confirmed SARS (66 men, 72 women; mean age, 39 years; age range, 20-83 years) were assessed. Radiographic appearances of pulmonary parenchymal abnormality, distribution, and extent of involvement on initial chest radiographs were documented. Recognizable patterns of radiographic progression were determined by comparing the overall mean percentage of lung involvement for each patient on serial radiographs. RESULTS: Initial chest radiographs were abnormal in 108 of 138 (78.3%) patients and showed air-space opacity. Lower lung zone (70 of 108, 64.8%) and right lung (82 of 108, 75.9%) were more commonly involved. In most patients, peripheral lung involvement was more common (81 of 108, 75.0%). Unifocal involvement (59 of 108, 54.6%) was more common than multifocal or bilateral involvement. No cavitation, lymphadenopathy, or pleural effusion was demonstrated. Four patterns of radiographic progression were recognized: type 1 (initial radiographic deterioration to peak level followed by radiographic improvement) in 97 of 138 patients (70.3%), type 2 (fluctuating radiographic changes) in 24 patients (17.4%), type 3 (static radiographic appearance) in 10 patients (7.3%), and type 4 (progressive radiographic deterioration) in seven patients (5.1%). Initial focal air-space opacity in 44 of 59 patients (74.6%) progressed to unilateral multifocal or bilateral involvement during treatment. CONCLUSION: Predominant peripheral location; common progression pattern from unilateral focal air-space opacity to unilateral multifocal or bilateral involvement during treatment; and lack of cavitation, lymphadenopathy, and pleural effusion are the more distinctive radiographic findings of SARS.

Adult↗
PubMed2003

Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease.

PURPOSE: To retrospectively analyze the thin-section computed tomographic (CT) features in patients with severe acute respiratory syndrome (SARS) at the authors' institution. MATERIALS AND METHODS: From March 11, 2003, to April 2, 2003, 74 patients with symptoms and signs suggestive of SARS underwent CT of the thorax; all underwent thin-section CT except for one patient who underwent conventional CT. Group 1 (n = 23) patients had symptoms of SARS in keeping with criteria from the Centers for Disease Control and Prevention and a positive chest radiograph. Group 2 (n = 17) patients had a high clinical suspicion of SARS but a normal radiograph. Group 3 (n = 34) patients had minor symptoms and a normal chest radiograph. The thin-section CT images were analyzed for ground-glass opacification or consolidation, lesion size in each lung segment, peripheral or central location, interstitial thickening, and other abnormalities. RESULTS: Thin-section CT scans were abnormal only for patients in groups 1 and 2. The patient with only conventional CT scans was in group 3; scans for group 3 patients were normal. Affected segments were predominantly in the lower lobes (91 of 149 affected segments). Common findings included ground-glass opacification, sometimes with consolidation, and interlobular septal and intralobular interstitial thickening. The size of each lesion and the total number of segments involved were smaller in group 2 patients. A majority of patients in group 1 (14 of 23) had mixed central and peripheral lesions. In group 2, however, peripheral lesions were more common (10 of 17). In both groups, a purely central lesion was uncommon (one of 23 in group 1 and two of 17 in group 2). CONCLUSION: Common thin-section CT features of SARS are ground-glass opacification and lower lobe and peripheral distribution.

Adolescent↗
PubMed2003

A major outbreak of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. METHODS: From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. RESULTS: There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). CONCLUSIONS: SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort.

Adult↗
PubMed2002

Validation of a tool to safely triage selected patients with chest pain to unmonitored beds.

OBJECTIVE: To externally validate a chest pain protocol that triages low risk patients with chest pain to an unmonitored bed. METHODS: Retrospective study of all patients admitted from the emergency department of a tertiary referral public teaching hospital with an admission diagnosis of 'unstable angina' or suspected ischemic chest pain. Data was collected on adverse outcomes and analysed on the basis of intention-to-treat according to the chest pain protocol. RESULTS: There were no life-threatening arrhythmias, cardiac arrests or deaths within the first 72 h of admission in the group assigned to an unmonitored bed by the chest pain protocol ([0/244]; 0.0%: 95% confidence interval 0.0-1.5%). Four patients had an uncomplicated myocardial infarction, two patients had recurrent ischemic chest pain and one patient developed acute pulmonary oedema ([7/244]; 2.9%: 95% confidence interval 1.2-5.8%). CONCLUSION: This retrospective study externally validated the chest pain protocol. Care in a monitored bed would not have altered outcomes for patients triaged to an unmonitored bed by the chest pain protocol. Compared to current guidelines, application of the chest pain protocol could increase the availability of monitored beds.

Aged↗
PubMed2002

Managing access block.

There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

Admitting Department, Hospital↗
PubMed2002

The Victorian emergency department collaboration.

OBJECTIVES: The aim of the project was to bring together 17 major emergency departments across Victoria, Australia, and the Australian Capital Territory to work together over an 8-month period to reduce both clinical and operational waits and delays, and to improve patient satisfaction. DESIGN: The collaborative was based on the Institute for Healthcare Improvement's Breakthrough Series, and utlilized their intellectual property and methodology adapted for the Australian setting. SETTING: The largest (by annual attendances) 17 emergency departments in the State of Victoria and one hospital in the Australian Capital Territory participated. STUDY PARTICIPANTS: Each hospital sent a team of three to five persons, which included the Emergency Department Medical Director and Nurse in Charge, and an Executive Sponsor to each learning session. INTERVENTIONS: The teams were required to attend four learning sessions, to participate during the action period in both clinical and operational improvement activities, and to report regularly in the form of data reports and conference calls. MAIN OUTCOME MEASURES: Each team selected at least one or two clinical topics for improvement and at least one operational project to undertake during the life of the collaborative. A patient satisfaction survey was commenced towards the end of the project. RESULTS: Forty-seven clinical projects were nominated during the life of the collaborative and 32 of these were completed, with 31 resulting in significant improvement or achieving target. Thirty-nine operational projects were nominated, 30 of which were completed, with 24 of these achieving improvement or target. Numerous additional achievements occurred, which evolved from the framework of supported collaboration. CONCLUSION: The spread of knowledge and innovation can be best facilitated rapidly by teams working together using a structured program in a supported environment.

Australian Capital Territory↗