Paleolakes and socioecological implications of last glacial "greening" of the South African interior.

Determining the timing and drivers of Pleistocene hydrological change in the interior of South Africa is critical for testing hypotheses regarding the presence, dynamics, and resilience of human populations. Combining geological data and physically based distributed hydrological modeling, we demonstrate the presence of large paleolakes in South Africa's central interior during the last glacial period, and infer a regional-scale invigoration of hydrological networks, particularly during marine isotope stages 3 and 2, most notably 55 to 39 ka and 34 to 31 ka. The resulting hydrological reconstructions further permit investigation of regional floral and fauna responses using a modern analog approach. These suggest that the climate change required to sustain these water bodies would have replaced xeric shrubland with more productive, eutrophic grassland or higher grass-cover vegetation, capable of supporting a substantial increase in ungulate diversity and biomass. The existence of such resource-rich landscapes for protracted phases within the last glacial period likely exerted a recurrent draw on human societies, evidenced by extensive pan-side artifact assemblages. Thus, rather than representing a perennially uninhabited hinterland, the central interior's underrepresentation in late Pleistocene archeological narratives likely reflects taphonomic biases stemming from a dearth of rockshelters and regional geomorphic controls. These findings suggest that South Africa's central interior experienced greater climatic, ecological, and cultural dynamism than previously appreciated and potential to host human populations whose archaeological signatures deserve systematic investigation.

Ripples at edges of blooming lilies and torn plastic sheets.

Ripples arise at edges of petals of blooming Lilium casablanca flowers and at edges of torn plastic sheets. In both systems, ripples are a consequence of excess length along the edge of a sheet. Through the use of time-lapse videos of blooming lilies and published images of torn plastic sheets, we find that ripples in both systems are well described by the scaling relationship a∝w(L-w), where a is amplitude, w is wavelength, and L is arc length. A phenomenological relationship previously reported for self-similar ripple patterns, namely ⟨a⟩∝⟨w⟩, can be recovered by assuming that buckling stress is constant. Excess length along petal edges can also influence their overall Gaussian curvature, such that petals invert from a cup shape to a saddle shape upon blooming. Previous simulations of these shape changes have assumed that petal thickness decreases at least quadratically. Here, we evaluate tomograms of several varieties of lily buds and find that this assumption is valid along the short axis of the buds, but not the long axis. A challenge of employing traditional tomography methods to measure petal thickness is that the sample is destroyed; a single bud cannot be followed through the entire blooming process. To address this challenge, we provide proof of principle that the nondestructive, label-free method of x-ray tomography produces high-contrast three-dimensional scans on time scales short enough to follow lily blooming.

Electronic cigarettes: A position statement from the Thoracic Society of Australia and New Zealand.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators.

Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I.

The calcium sensitivity of cardiac and skeletal muscle is reduced during cytosolic acidosis, and this inhibition is more pronounced in cardiac muscle. Replacing cardiac troponin I with skeletal troponin I reduces the pH sensitivity of cardiac muscle. This diminished pH sensitivity depends on a single amino acid difference in troponin I: an alanine in cardiac and a histidine in skeletal. Studies suggested that when this histidine is protonated, it forms an electrostatic interaction with glutamate 19 on the surface of cardiac troponin C. Structures of the skeletal and cardiac troponin complexes show very different conformations for the region of troponin I surrounding this residue. In this study, we determined the structure of skeletal troponin I bound to cardiac troponin C. Skeletal troponin I is found to bind to cardiac troponin C with histidine 130 in close proximity to glutamate 19. This conformation is homologous to the crystal structure of the skeletal troponin complex; but different than in the cardiac complex. We show that an A162H variant of cardiac troponin I adopts a conformation similar to the skeletal structure. The implications of these structural differences in the context of cardiac muscle regulation are discussed.

Abnormal vocal cord movement treated with botulinum toxin in patients with asthma resistant to optimised management.

BACKGROUND AND OBJECTIVE: Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. METHODS: In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. RESULTS: ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. CONCLUSIONS: Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined. Nontypeable Haemophilus influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients with COPD. OBJECTIVE: We sought to measure the response of lung tissue T cells to stimulation with NTHi. METHODS: We obtained lung tissue from 69 subjects having lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without COPD were classified as control subjects. The lung tissue was dispersed into single-cell suspensions and stimulated with live NTHi. Cells were labeled with antibodies for 5 important inflammatory mediators in patients with COPD and analyzed by using flow cytometry. RESULTS: NTHi produced strong activation of both TH cells and cytotoxic T cells in the COPD cohort. The COPD cohort had significantly higher levels of cells producing TNF-α, IL-13, and IL-17 in both T-cell subsets. When control subjects were divided into those with and without a significant smoking history and compared with patients with COPD, there was a progressive increase in the numbers of T cells producing cytokines from nonsmoking control subjects to smoking control subjects to patients with COPD. CONCLUSION: NTHi activates lung T cells in patients with COPD. This proinflammatory profibrotic response might be a key cause of inflammation in patients with COPD and has implications for treatment.

Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives: This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design: Retrospective consecutive patient cohort analysis. Methods: We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results: During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion: EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Outcome and approach of small-bowel stricture dilation using balloon-assisted endoscopy in patients with Crohn's disease This study investigated the safety and success of using balloon-assisted endoscopy as a method to dilate small bowel strictures in patients with Crohn's disease. As a secondary outcome, we compared the overall safety and success between two different types of endoscopic systems: the single- and double-balloon systems.

Elucidation of isoform-dependent pH sensitivity of troponin i by NMR spectroscopy.

Myocardial ischemia is characterized by reduced blood flow to cardiomyocytes, which can lead to acidosis. Acidosis decreases the calcium sensitivity and contractile efficiency of cardiac muscle. By contrast, skeletal and neonatal muscles are much less sensitive to changes in pH. The pH sensitivity of cardiac muscle can be reduced by replacing cardiac troponin I with its skeletal or neonatal counterparts. The isoform-specific response of troponin I is dictated by a single histidine, which is replaced by an alanine in cardiac troponin I. The decreased pH sensitivity may stem from the protonation of this histidine at low pH, which would promote the formation of electrostatic interactions with negatively charged residues on troponin C. In this study, we measured acid dissociation constants of glutamate residues on troponin C and of histidine on skeletal troponin I (His-130). The results indicate that Glu-19 comes in close contact with an ionizable group that has a pK(a) of ∼6.7 when it is in complex with skeletal troponin I but not when it is bound to cardiac troponin I. The pK(a) of Glu-19 is decreased when troponin C is bound to skeletal troponin I and the pK(a) of His-130 is shifted upward. These results strongly suggest that these residues form an electrostatic interaction. Furthermore, we found that skeletal troponin I bound to troponin C tighter at pH 6.1 than at pH 7.5. The data presented here provide insights into the molecular mechanism for the pH sensitivity of different muscle types.

Tsetse-transmitted trypanosomes--their biology, disease impact and control.

Tsetse-transmitted trypanosome infections of man and animals occur across large areas of sub-Saharan Africa and are a major cause of ill-health and death. Although many details of the biology of tsetse-transmitted trypanosomes and the diseases they cause have been clearly established their control has proved extremely difficult. In part this is because trypanosomes show amazing antigenic variation of their surface coat and this has prevented the development of an effective vaccine. Also the few drugs which are available for treatment are unsatisfactory and often have severe side-effects. Significant progress has been made through tsetse control but such programmes are expensive and frequently re-infestation occurs. There is an urgent need for more effective disease diagnostic methods, new safer drugs and more sustained international support for integrated control programmes.

Abnormal vocal cord function in difficult-to-treat asthma.

RATIONALE: Upper airway dysfunction may complicate asthma but has been largely ignored as an etiological factor. Diagnosis using endoscopic evaluation of vocal cord function is difficult to quantify, with limited clinical application. OBJECTIVES: A novel imaging technique, dynamic 320-slice computerized tomography (CT), was used to examine laryngeal behavior in healthy individuals and individuals with asthma. METHODS: Vocal cord movement was imaged using 320-slice CT larynx. Healthy volunteers were studied to develop and validate an analysis algorithm for quantification of normal vocal cord function. Further studies were then conducted in 46 patients with difficult-to-treat asthma. MEASUREMENTS AND MAIN RESULTS: Vocal cord movement was quantified over the breathing cycle by CT using the ratio of vocal cord diameter to tracheal diameter. Normal limits were calculated, validated, and applied to evaluate difficult-to-treat asthma. Vocal cord movement was abnormal with excessive narrowing in 23 of 46 (50%) patients with asthma and severe in 9 (19%) patients (abnormal > 50% of inspiration or expiration time). Imaging also revealed that laryngeal dysfunction characterized the movement abnormality rather than isolated vocal cord dysfunction. CONCLUSIONS: Noninvasive quantification of laryngeal movement was achieved using CT larynx. Significant numbers of patients with difficult-to-treat asthma had excessive narrowing of the vocal cords. This new approach has identified frequent upper airway dysfunction in asthma with potential implications for disease control and treatment.

Lung diffusing capacity in adult bronchiectasis: a longitudinal study.

BACKGROUND: Recent studies described a progressive decline in lung volumes in adult bronchiectasis. Interstitial lung disease is also a feature of bronchiectasis, but whether this is associated with a decline in lung diffusing capacity (measured as the diffusing capacity of the lung for carbon monoxide [D(LCO)]) is not well known. OBJECTIVE: To assess longitudinal decline in diffusing capacity of the lung for carbon monoxide (D(LCO)) in adult bronchiectasis. METHODS: Sixty-one subjects had a detailed baseline clinical and laboratory assessment, then were followed regularly with clinical and lung-function assessment for a median 7 years. RESULTS: Baseline spirometry demonstrated mild obstructive lung disease, with a mean FEV(1) of 72% of predicted, mean forced vital capacity 87% of predicted, and normal D(LCO) (mean D(LCO) 88% of predicted, and mean D(LCO) adjusted for alveolar volume [D(LCO)/V(A)] 100% of predicted). There was an accelerated decline in D(LCO) and D(LCO)/V(A) over the 7-year period. The median D(LCO) decline was 2.9% of predicted per year (95% CI 2.3-4.1% of predicted per year). The median D(LCO)/V(A) decline was 2.4% of predicted per year (95% CI 2.1-4.0% of predicted per year). There was a significant relationship between D(LCO) decline and age and decline in FEV(1). CONCLUSIONS: In our cohort of patients with bronchiectasis there was a progressive D(LCO) decline.

Aroma Acupoint Therapy for Symptom Management with Adolescent Patients: Early Experiences from School-Based Health Centers.

Objectives: The American Academy of Pediatrics has long recognized a need for more resources for integrative medicine for health care providers and for patients. The aim of this study was to introduce Aroma Acupoint Therapy (AAT)-a relatively new integrative medicine modality using essential oils to activate acupoints-and to describe the early experiences of providers using AAT for adolescents at school-based health centers (SBHCs). Materials and Methods: This was a case series of 15 adolescents treated with 1 of 2 AAT specific protocols plus standard medical therapy between April 2018 and February 2019 at SBHCs. Of these 15 patients, ages 12-19, 14 were female. Clinical characteristics and treatment courses were abstracted by retrospective review of the patients' electronic medical records. The main outcomes and measures for this research were clinical characteristics, treatment courses and pre- and post-treatment pain scores for adolescents treated with AAT. Results: All 15 patients had nonspecific symptoms, including headaches, menstrual cramps, nausea, shortness of breath, chest pain, back pain, or dizziness. Pain scores were recorded in 8 of 15 encounters, and suggested improvements in most patients. Subjective documentation by the providers also suggested that most of these patients had reduced symptoms. Conclusions: With the call for nonopiate and integrative approaches to pain management, there is an urgent need to study the effectiveness of such modalities, such as AAT. It is safe, inexpensive, easy to learn, and is well-received by both health care providers and patients.

The lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism.

Coordination of outer membrane constriction with septation is critical to faithful division in Gram-negative bacteria and vital to the barrier function of the membrane. This coordination requires the recruitment of the peptidoglycan-binding outer-membrane lipoprotein Pal at division sites by the Tol system. Here, we show that Pal accumulation at Escherichia coli division sites is a consequence of three key functions of the Tol system. First, Tol mobilises Pal molecules in dividing cells, which otherwise diffuse very slowly due to their binding of the cell wall. Second, Tol actively captures mobilised Pal molecules and deposits them at the division septum. Third, the active capture mechanism is analogous to that used by the inner membrane protein TonB to dislodge the plug domains of outer membrane TonB-dependent nutrient transporters. We conclude that outer membrane constriction is coordinated with cell division by active mobilisation-and-capture of Pal at division septa by the Tol system.

Dual-energy X-ray absorptiometry is the method of choice to assess body composition in COPD.

BACKGROUND AND OBJECTIVE: Mortality and morbidity in COPD have been related to reduced FEV1 as well as indices of body composition. Different techniques used to evaluate body composition may vary in accuracy, particularly in conditions with altered fluid balance such as COPD. We hypothesized that direct measurement of fat-free mass index (FFMI) by dual-energy X-ray absorptiometry (DEXA) would provide superior assessment of body composition in COPD. METHODS: We measured body composition in 31 patients with COPD randomly selected from a teaching hospital clinic. To estimate total body water (TBW) and FFMI, skin-fold anthropometry, bioelectrical impedance analysis (BIA) with Schols and Lukaski equations as well as DEXA, total body potassium by whole-body gamma-counting (TBK) and in vivo neutron activation analysis were used. Combined body composition methods providing precise estimations of TBW were used for comparisons. Bland-Altman analyses, ANOVA and chi2-testing were used to examine data. RESULTS: Mean BMI was 27.6 +/- 5.34 kg/m2 (mean +/- SD). Estimations of TBW were similar using Schols BIA or by using combined body composition methods. FFMI did not vary significantly between grades of COPD severity but was significantly different when assessed using DEXA and other methods. Calculated FFM hydration was significantly different from the fixed hydration factor used to calculate FFMI from BIA TBW (P < 0.05). CONCLUSION: The Schols BIA method incorporates a fixed hydration factor that may lead to an erroneous estimation of FFMI with ensuing clinical implications. DEXA can be used to obtain accurate and comprehensive assessments of body composition and should be the preferred investigation in COPD.

Diagnosis of vocal cord dysfunction in asthma with high resolution dynamic volume computerized tomography of the larynx.

BACKGROUND AND OBJECTIVE: Vocal cord dysfunction (VCD) often masquerades as asthma and reports have suggested that up to 30% of patients with asthma may have coexistent VCD. Diagnosis of VCD is difficult, in part because it involves laryngoscopy which has practical constraints, and there is need for rapid non-invasive diagnosis. High speed 320-slice volume CT demonstrates laryngeal function during inspiration and expiration and may be useful in suspected VCD. METHODS: Endoscopy and high resolution 320-slice dynamic volume CT were used to examine and compare laryngeal anatomy and movement in a case of subglottic stenosis and in a patient with confirmed VCD. Nine asthmatics with ongoing symptoms and suspected VCD also underwent 320-slice dynamic volume CT. Tracheal and laryngeal anatomy and movement were evaluated and luminal areas were measured. Reductions in vocal cord luminal area >40%, lasting for >70% duration of inspiration/expiration, were judged to be consistent with VCD. RESULTS: Studies of subglottic tracheal stenosis validated anatomical similarities between endoscopy and CT images. Endoscopy and 320-slice volume CT also provided comparable dynamic images in a patient with confirmed VCD. A further nine patients with a history of severe asthma and suspected VCD were studied using CT. Four patients had evidence of VCD and the median reduction of luminal area during expiration was 78.2% (range 48.2-92.5%) compared with 10.4% (range 4.7-30%) in the five patients without VCD. Patients with VCD had no distinguishing clinical characteristics. CONCLUSIONS: Dynamic volume CT provided explicit images of the larynx, distinguished function of the vocal cords during the respiratory cycle and could identify putative VCD. The technique will potentially provide a simple, non-invasive investigation to identify laryngeal dysfunction, permitting improved management of asthma.

Phenotypes of adult bronchiectasis: onset of productive cough in childhood and adulthood.

Bronchiectasis is a heterogeneous disorder with a large number of etiologic factors. The main symptom is a chronic productive cough. The aim of this study was to describe the phenotypes of patients with bronchiectasis who had developed a chronic productive cough in childhood (before 16 years of age) compared with those who had developed a productive cough as adults. One hundred and eighty-two subjects with bronchiectasis diagnosed by computed tomography scanning were studied. Subjects all had a detailed clinical review and assessment of potential etiologic factors performed by the investigators. There were 107 (59%) subjects who developed a chronic productive cough in childhood and 75 (41%) subjects who developed a chronic productive cough in adulthood. There were significant differences in a number of parameters between the two groups including duration of cough, frequency of exacerbations, presence of rhinosinusitis, crackles on examination and lung function. The adult group could be further divided into those who had developed a cough whilst smoking and those who had no obvious relationship with smoking. In conclusion there were a number of significant differences between the child onset and adult onset group that may reflect different phenotypes of bronchiectasis.

Nascent ß Structure in the Elongated Hydrophobic Region of a Gerstmann-Sträussler-Scheinker PrP Allele.

Prion diseases are neurodegenerative disorders caused by the misfolding of the cellular prion protein (PrPC). Gerstmann-Sträussler-Scheinker syndrome is an inherited prion disease with one early-onset allele (HRdup) containing an eight-amino-acid insertion; this LGGLGGYV insert is positioned after valine 129 (human PrPC sequence) in a hydrophobic tract in the natively disordered region. Here we have characterized the structure and explored the molecular motions and dynamics of HRdup PrP and a control allele. High-resolution NMR data suggest that the core of HRdup has a canonical PrPC structure, yet a nascent ß-structure is observed in the flexible elongated hydrophobic region of HRdup. In addition, using mouse PrPC sequence, we observed that a methionine/valine polymorphism at codon 128 (equivalent of methionine/valine 129 in human sequence) and oligomerization caused by high protein concentration affects conformational exchange dynamics at residue G130. We hypothesize that with the ß-structure at the N-terminus, the hydrophobic region of HRdup can adopt a fully extended configuration and fold back to form an extended ß-sheet with the existing ß-sheet. We propose that these structures are early chemical events in disease pathogenesis.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia.

BACKGROUND: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.