Frequency of non-aureus staphylococci and mammaliicocci species isolated from quarter clinical mastitis: a six-year retrospective study.

Non-aureus staphylococci and mammaliicocci (NASM) are the most frequently isolated bacterial group from bovine milk samples. Most studies focus on subclinical mastitis caused by NASM, however NASM can cause clinical mastitis (CM) as well. We evaluated retrospective data from 6 years (2017-2022) to determine the species and frequency of NASM isolated from quarter bovine CM. The data comprised of microbiological results from quarter CM samples routinely submitted to Quality Milk Production Services (QMPS), Cornell University, NY, US, for microbial identification by MALDI-TOF MS. A total of 9,909 microbiological results from 410 dairy herds were evaluated. Our results showed that 29 distinct NASM species were identified, with the 8 most prevalent NASM species being Staphylococcus chromogenes, S. haemolyticus, S. simulans, S. epidermidis, S. sciuri (now Mammaliicoccus sciuri), S. agnetis/S. hyicus, S. borealis, and S. xylosus. The NASM distribution remained similar among seasons, but the frequency of NASM CM cases was higher during the summer. Our results showed different patterns of variations in the isolation frequency over time, depending on the bacterial species: increasing or decreasing trends, cyclic fluctuations, and except for S. borealis, a significant seasonality effect for our study's most prevalent NASM was observed. This study showed that S. chromogenes remains the most frequent (43%) NASM species identified from bovine CM, followed by S. haemolyticus (18%), and S. simulans (12%).

Utilizing machine learning to improve clinical trial design for acute respiratory distress syndrome.

Heterogeneous patient populations, complex pharmacology and low recruitment rates in the Intensive Care Unit (ICU) have led to the failure of many clinical trials. Recently, machine learning (ML) emerged as a new technology to process and identify big data relationships, enabling a new era in clinical trial design. In this study, we designed a ML model for predictively stratifying acute respiratory distress syndrome (ARDS) patients, ultimately reducing the required number of patients by increasing statistical power through cohort homogeneity. From the Philips eICU Research Institute (eRI) database, no less than 51,555 ARDS patients were extracted. We defined three subpopulations by outcome: (1) rapid death, (2) spontaneous recovery, and (3) long-stay patients. A retrospective univariate analysis identified highly predictive variables for each outcome. All 220 variables were used to determine the most accurate and generalizable model to predict long-stay patients. Multiclass gradient boosting was identified as the best-performing ML model. Whereas alterations in pH, bicarbonate or lactate proved to be strong predictors for rapid death in the univariate analysis, only the multivariate ML model was able to reliably differentiate the disease course of the long-stay outcome population (AUC of 0.77). We demonstrate the feasibility of prospective patient stratification using ML algorithms in the by far largest ARDS cohort reported to date. Our algorithm can identify patients with sufficiently long ARDS episodes to allow time for patients to respond to therapy, increasing statistical power. Further, early enrollment alerts may increase recruitment rate.

Mycoplasma species isolated from bovine milk collected from US dairy herds between 2016 and 2019.

Determining the species of mycoplasma isolated from culture-positive milk samples is important for understanding the clinical significance of their detection. Between August 2016 and December 2019, 214,518 milk samples from 2,757 dairy herds were submitted to Quality Milk Production Services (QMPS) at Cornell University for mycoplasma culture. From these samples, 3,728 collected from 204 herds were culture positive. Based on the request of herd managers, owners, or veterinarians, 889 isolates from 98 herds were subjected to molecular identification by PCR and amplicon sequencing. The largest proportion of the identified isolates were from New York State (78.1%), while the others came from the eastern United States (17.8%), Texas (2.0%), and New Mexico (2.1%). As expected, Mycoplasma spp. were the most common (855 isolates, 96.2%) and Acholeplasma spp. accounted for the remainder (34 isolates, 3.8%). Mycoplasma bovis was the most prevalent Mycoplasma species (75.1%), followed by M. bovigenitalium (6.5%), M. canadense (5.9%), M. alkalescens (5%), M. arginini (1.7%), M. californicum (0.1%), and M. primatum (0.1%). A portion of the isolates were confirmed as Mycoplasma spp. other than M. bovis but were not identified at the species level (16 isolates, 1.8%) because further information was not requested by the manager, owner, or veterinarian. Mycoplasma bovis was the only species identified in 59 of the 98 herds. However, more than 1 Mycoplasma sp. was identified in 29 herds, suggesting that herd infection with 2 or more mycoplasmas is not uncommon. Moreover, a Mycoplasma sp. other than M. bovis was the only species identified in 8 herds. From the subset of 889 mycoplasma culture-positive isolates from 98 herds, we determined that over a third of the herds had either more than 1 Mycoplasma sp. or a Mycoplasma sp. other than M. bovis detected in their milk samples. In conclusion, we observed that M. bovis is the most common pathogenic Mycoplasma species found in mastitic milk, but other Mycoplasma species are not uncommon. Our results suggest that it is critical to test milk samples for mycoplasmas using diagnostic tests able to identify both the genus and the species.

Overcoming challenges to support us resumption of high specific activity cobalt-60.

Domestic production of high specific activity 60Co was halted after a target rupture in 2012 at the Advanced Test Reactor (ATR). The Isotope Program (IP) within the US Department of Energy (DOE) Office of Science tasked a multilaboratory team of researchers and managers from Oak Ridge and Idaho National Laboratories with the redesign the radioisotope capsule. The objective of this effort was to create a more robust and reliable design, compared to the pre-2012 target. The team successfully completed this task to produce the DOE-IP cobalt (Co) production capsule design. Furthermore, 66 capsules were successfully fabricated by Oak Ridge National Laboratory (ORNL) and delivered to Idaho National Laboratory (INL) for irradiation in the ATR between January 2014 and October 2016. This paper describes the efforts of the team to prepare and disposition the two initial DOE-IP Co production capsules that were processed in March 2020. These efforts include performing accurate production predictions, experimentally validating predictions with assay measurements, shipping with the Orano-furnished Battelle Energy Alliance Research Reactor shipping package, and disassembling capsules at the isotope vendor site.

Emergent Premedication for Contrast Allergy Prior to Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Management of contrast media allergies may lead to treatment delays in patients with acute ischemic stroke undergoing endovascular therapy. The optimal premedication strategy remains unclear. The aim of this report was to analyze our experience with emergent administration of premedication regimens before endovascular therapy. MATERIALS AND METHODS: We retrospectively reviewed prospective data for all patients undergoing endovascular therapy from 2012 to 2019 at an academic comprehensive stroke center. Records of patients with documented contrast allergy were reviewed and analyzed. Data collected included stroke risk factors and characteristics, historical contrast reaction details, premedication regimens administered, and signs or symptoms of allergic reaction developing post-endovascular therapy. Hospital arrival time to endovascular therapy was compared with that in those who did not have a history of contrast allergy. RESULTS: We analyzed 1521 patients undergoing endovascular therapy; 60 (4%) had documented contrast allergies and constituted the study cohort. The median age was 73 years (interquartile range, 66-81 years), and 65% were women. The median time from premedication to contrast was 24 minutes (interquartile range, 0-36 minutes). Forty-three patients (72%) proceeded directly to endovascular therapy; in 17 patients, the first contrast exposure was CTA. Time from hospital arrival to endovascular therapy was not slower for patients with documented allergies (96 versus 134 minutes, P = .32). No patients experienced a contrast media reaction. CONCLUSIONS: In a single-institution cohort study of 60 consecutive patients with documented contrast allergies undergoing endovascular therapy with emergent premedication en route to (or in) the neuroangiography suite, no patients experienced allergic symptoms. This pragmatic approach may be safe for patients who have documented contrast media allergies.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS: Overall, 128 aneurysms in 128 patients (median age, 62 years) were treated with 138 stents. Risk factors included smoking (59.4%), multiple aneurysms (27.3%), and family history of aneurysms (16.4%). Most patients were treated electively (93.7%), and 8 (6.3%) underwent treatment within 2 weeks of subarachnoid hemorrhage. Previous aneurysm treatment failure was present in 21% of cases. Wide-neck aneurysms (80.5%), small aneurysm size (<7 mm, 76.6%), and bifurcation aneurysm location (basilar apex, 28.9%; anterior communicating artery, 27.3%; and middle cerebral artery bifurcation, 12.5%) were common. A single stent was used in 92.2% of cases, and a single catheter for both stent placement and coiling was used in 59.4% of cases. Technical complications during stent deployment occurred in 4.7% of cases; symptomatic thromboembolic stroke, in 2.3%; and symptomatic hemorrhage, in 0.8%. Favorable Raymond grades (Raymond-Roy occlusion classification) I and II were achieved in 82.9% at discharge and 89.5% at last follow-up. mRS ≤2 was determined in 96.9% of patients at last follow-up. The immediate Raymond-Roy occlusion classification grade correlated with aneurysm location (P < .0001) and rupture status during treatment (P = .03). CONCLUSIONS: This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

Magnetic Force Sensing Using a Self-Assembled Nanowire.

We present a scanning magnetic force sensor based on an individual magnet-tipped GaAs nanowire (NW) grown by molecular beam epitaxy. Its magnetic tip consists of a final segment of single-crystal MnAs formed by sequential crystallization of the liquid Ga catalyst droplet. We characterize the mechanical and magnetic properties of such NWs by measuring their flexural mechanical response in an applied magnetic field. Comparison with numerical simulations allows the identification of their equilibrium magnetization configurations, which in some cases include magnetic vortices. To determine a NW's performance as a magnetic scanning probe, we measure its response to the field profile of a lithographically patterned current-carrying wire. The NWs' tiny tips and their high force sensitivity make them promising for imaging weak magnetic field patterns on the nanometer-scale, as required for mapping mesoscopic transport and spin textures or in nanometer-scale magnetic resonance.

Comparison of two prognostic models in trauma outcome.

BACKGROUND: The Trauma Audit and Research Network (TARN) in the UK publicly reports hospital performance in the management of trauma. The TARN risk adjustment model uses a fractional polynomial transformation of the Injury Severity Score (ISS) as the measure of anatomical injury severity. The Trauma Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared the anatomical injury components of the TARN model with the TMPM. METHODS: Data from the National Trauma Data Bank for 2011-2015 were analysed. Probability of death was estimated for the TARN fractional polynomial transformation of ISS and compared with the TMPM. The coefficients for each model were estimated using 80 per cent of the data set, selected randomly. The remaining 20 per cent of the data were used for model validation. TMPM and TARN were compared using calibration curves, measures of discrimination (area under receiver operating characteristic curves; AUROC), proximity to the true model (Akaike information criterion; AIC) and goodness of model fit (Hosmer-Lemeshow test). RESULTS: Some 438 058 patient records were analysed. TMPM demonstrated preferable AUROC (0·882 for TMPM versus 0·845 for TARN), AIC (18 204 versus 21 163) and better fit to the data (32·4 versus 153·0) compared with TARN. CONCLUSION: TMPM had greater discrimination, proximity to the true model and goodness-of-fit than the anatomical injury component of TARN. TMPM should be considered for the injury severity measure for the comparative assessment of trauma centres.

Imaging Stray Magnetic Field of Individual Ferromagnetic Nanotubes.

We use a scanning nanometer-scale superconducting quantum interference device to map the stray magnetic field produced by individual ferromagnetic nanotubes (FNTs) as a function of applied magnetic field. The images are taken as each FNT is led through magnetic reversal and are compared with micromagnetic simulations, which correspond to specific magnetization configurations. In magnetic fields applied perpendicular to the FNT long axis, their magnetization appears to reverse through vortex states, that is, configurations with vortex end domains or in the case of a sufficiently short FNT with a single global vortex. Geometrical imperfections in the samples and the resulting distortion of idealized magnetization configurations influence the measured stray-field patterns.

Collaborative stepped care for somatoform disorders: A pre-post-intervention study in primary care.

OBJECTIVE: The successful management of somatoform disorders in primary care is often limited due to low diagnostic accuracy, delayed referral to psychotherapy, and unstructured overuse of health care. This study aimed to investigate the feasibility of establishing a collaborative stepped health care network for somatoform disorders, and its impact on the diagnostic process and treatment recommendations in primary care. METHOD: The Network for Somatoform and Functional Disorders (Sofu-Net) was established to connect 41 primary care physicians (PCP), 35 psychotherapists, and 8 mental health clinics. To evaluate Sofu-Net, primary care patients at high risk of having a somatoform disorder were identified using the Patient Health Questionnaire, and were assessed in detail at the patient and PCP level. Discussion of psychosocial distress in the consultations, diagnostic detection rates and treatment recommendations were compared before and 12 months after establishing the network. RESULTS: Out of the pre- (n=1645) and 12-months-post Sofu-Net patient samples (n=1756), 267 (16.2%) and 269 (15.3%) high-risk patients were identified. From these, 156 and 123 patients were interviewed and information was assessed from their PCP. Twelve months after Sofu-Net establishment, high-risk patients more frequently discussed psychosocial distress with their PCP (63.3% vs. 79.2%, p<.001). PCPs prescribed more antidepressants (3.8% vs. 25.2%, p<.001) and less benzodiazepines (21.8% vs. 6.5%, p<.001). Sofu-Net did not affect PCP's diagnostic detection rates or recommendation to initiate psychotherapy. CONCLUSION: The study results indicate feasibility of an interdisciplinary network for somatoform disorders. Collaborative care networks for somatoform disorders have the potential to improve doctor-patient-communication and prescription behavior.

Assessment of microsatellites in estimating inter- and intraspecific variation among Neotropical Crocodylus species.

We tested microsatellites that were developed for the saltwater crocodile (Crocodylus porosus) for cross-species amplification and to provide an estimate of inter- and intraspecific variation among four species of Neotropical crocodiles (C. rhombifer, C. intermedius, C. acutus, and C. moreletii). Our results indicated that with the exception of 2 loci in C. intermedius, all 10 microsatellite loci were successfully amplified in the 4 species, producing a set of variably sized alleles that ranged in number between 2 and 14 alleles per locus. Similarly, private alleles (i.e., unique alleles) also were reported in all 4 species for at least 3 loci. The mean observed and expected heterozygosities (averaged across species for all 10 loci combined) ranged from 0.39 to 0.77 and from 0.44 to 0.78, respectively. In addition to this, we evaluated these microsatellites in 2 populations of C. acutus and C. moreletii to assess their utility in estimating intraspecific levels of polymorphisms. These microsatellites also showed considerable allelic variation in population level analysis. The set of 10 microsatellite loci in our study had the potential to be used as a tool in population and conservation genetic studies of Neotropical crocodiles.

Noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows.

The objective of this study was to evaluate the noninferiority of 2 intramammary treatments for nonsevere clinical mastitis. The 2 treatments were a first-generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third-generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d). A total of 296 cases on 7 farms met the enrollment criteria for the study. Streptococcus dysgalactiae was the most common bacterial species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or ceftiofur hydrochloride via intramammary infusion according to label standards. Bacteriological cure was defined based on 2 posttreatment milk samples taken at 10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur was shown for bacteriological cure of gram-positive cases and for clinical cure of all cases. Ceftiofur showed a significantly higher bacteriological cure in gram-negative cases. Treatments showed no significant difference in bacteriological cure of all cases and in time to exit from the study, where the absence of a difference does not imply noninferiority. Based on the findings from this study, farm-specific treatment protocols that differ for gram-positive and gram-negative cased may be developed.

Improved generation of patient-specific induced pluripotent stem cells using a chemically-defined and matrigel-based approach.

Reprogramming of somatic cells into patient-specific pluripotent analogues of human embryonic stem cells (ESCs) emerges as a prospective therapeutic angle in molecular medicine and a tool for basic stem cell biology. However, the combination of relative inefficiency and high variability of non-defined culture conditions precluded the use of this technique in a clinical setting and impeded comparability between laboratories. To overcome these obstacles, we sequentially devised a reprogramming protocol using one lentiviral-based polycistronic reprogramming construct, optimized for high co-expression of OCT4, SOX2, KLF4 and MYC in conjunction with small molecule inhibitors of non-permissive signaling cascades, such as transforming growth factor ß (SB431542), MEK/ERK (PD0325901) and Rho-kinase signaling (Thiazovivin), in a defined extracellular environment. Based on human fetal liver fibroblasts we could efficiently derive induced pluripotent stem cells (iPSCs) within 14 days. We attained efficiencies of up to 10.97±1.71% resulting in 79.5- fold increase compared to non-defined reprogramming using four singular vectors. We show that the overall increase of efficiency and temporal kinetics is a combinatorial effect of improved lentiviral vector design, signaling inhibition and definition of extracellular matrix (Matrigel®) and culture medium (mTESR®1). Using this protocol, we could derive iPSCs from patient fibroblasts, which were impermissive to classical reprogramming efforts, and from a patient suffering from familial platelet disorder. Thus, our defined protocol for highly efficient reprogramming to generate patient-specific iPSCs, reflects a big step towards therapeutic and broad scientific application of iPSCs, even in previously unfeasible settings.

[Scientific monitoring of the visitation procedure in inpatient rehabilitation centres of the German statutory pension insurance fund--the "Visit II" Project]. / Wissenschaftliche Begleitung der Weiterentwicklung des Visitationsverfahrens für Reha-Kliniken der Deutschen Rentenversicherung Bund--Das Projekt "Visit II".

Visitation procedures are an established method of external quality assurance. They have been conducted for many years in the German statutory pension insurance's medical rehabilitation centres and have continuously been refined and standardized. The overall goal of the visitation procedure implemented by the German statutory pension fund is to ensure compliance with defined quality standards as well as information exchange and counselling of rehabilitation centres. In the context of advancing the visitation procedure in the German statutory pension funds' medical rehabilitation centres, the "Visit II" Project was initiated to evaluate the perspectives and expectations of the various professional groups involved in the visitations and to modify the materials used during visitations (documentation form and manual). Evaluation data from the rehabilitation centres visited in 2008 were gathered using both written surveys (utilization analysis) and telephone-based interviews with administration managers and chief physicians. The utilization analysis procedure was evaluated with regard to its methodological quality. In addition, the pension insurance physicians in charge of patient allocation during socio-medical assessment were surveyed with regard to potential needs for revision of the visitation procedure. Data collection was complemented by expert panels with auditors. Interviews with users as part of the formative evaluation of the visitation procedure showed positive results regarding acceptance and applicability of the visitations as well as of the utilization analysis procedures. Various suggestions were made with regard to modification and revision of the visitation materials, that could be implemented in many cases. Documentation forms were supplemented by current scientifically-based topics in rehabilitation (e. g., vocationally oriented measures), whereas items with minor relevance were skipped. The manual (for somatic indications) was thoroughly revised. The transparent presentation of visitation processes and visitation criteria has proven to be a useful basis for strengthening the cooperation between the statutory pension insurance funds and the rehabilitation centres. Moreover, it is a helpful tool for the systematic and continuous advancement of this complex method by including all parties involved.

[The manual "Problematic use and dependence of prescipted drugs" in daily routine care - a study among participants in a training to qualify in "primary addiction treatment"]. / Der Leitfaden "Medikamente - schädlicher Gebrauch und Abhängigkeit" im ärztlichen Arbeitsalltag. Eine Studie unter Kursteilnehmern zum Erwerb der Zusatzweiterbildung "Suchtmedizinische Grundversorgung".

BACKGROUND: To strengthen the position of physicians regarding problematic use and dependence of prescripted drugs a manual was issued by the German Medical Association in 2007.  A study among participants in a training to qualify in "primary addiction treatment" was conducted. The utilisation of the manual, its relevance for routine care and self-estimated changes in drug prescription were examined. METHODS: All 542 participants in training courses between 1.9.2008 and 31.12.2009 were asked about participation in a survey 12 weeks later. A number of 267 took part in this investigation. RESULTS: A proportion of 60,7 % among GPs that received the manual dealt with them beyond the training course. From 178 physicians, who confirmed the provision of drug prescription, a number of 56 stated changes in their drug prescription. A higher probabilty for changes in drug prescription was given in case of a high percentage of new informations that could be culled from the manual. CONCLUSION: The interest for the manual beyond the training course and the amount of self-estimated changes in drug prescription should encourage to use this within training measures in a systematic way.

Ethnic variations in acute ischemic stroke: findings from the National Acute Stroke Israeli Survey (NASIS).

BACKGROUND: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations. METHODS: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data. RESULTS: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19-2.50) and have diabetes (OR = 1.41; 95% CI: 1.01-1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11-2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56-5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39-3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14-2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35-4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups. CONCLUSIONS: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs.

Generation and characterization of a humanized PPARδ mouse model.

BACKGROUND AND PURPOSE: Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH: Human PPARδ function in lipid metabolism was assessed at baseline, after fasting or when challenged with the GW0742 compound in mice fed a chow diet or high-fat diet (HFD). KEY RESULTS: Analysis of PPARδ mRNA levels revealed a hypomorph expression of human PPARδ in liver, macrophages, small intestine and heart, but not in soleus and quadriceps muscles, white adipose tissue and skin. PPARδ KI mice displayed a small decrease of high-density lipoprotein-cholesterol whereas other lipid parameters were unaltered. Plasma metabolic parameters were similar in wild-type and PPARδ KI mice when fed chow or HFD, and following physiological (fasting) and pharmacological (GW0742 compound) activation of PPARδ. Gene expression profiling in liver, soleus muscle and macrophages showed similar gene patterns regulated by mouse and human PPARδ. The anti-inflammatory potential of human PPARδ was also similar to mouse PPARδ in liver and isolated macrophages. CONCLUSIONS AND IMPLICATIONS: These data indicate that human PPARδ can compensate for mouse PPARδ in the regulation of lipid metabolism and inflammation. Overall, this novel PPARδ KI mouse model shows full responsiveness to pharmacological challenge and represents a useful tool for the preclinical assessment of PPARδ activators with species-specific activity.

Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema.

The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (D(L,CO)) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n = 321), 6 months (n = 211) and 12 months (n = 144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p = 0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in D(L,CO) or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV(1) predicted mortality (HR 3.7, p = 0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in D(L,CO). For CPFE patients, change in FEV(1) was the best predictor of mortality.

The molecular basis of white pericarps in African domesticated rice: novel mutations at the Rc gene.

Repeated phenotypic evolution can occur at both the inter- and intraspecific level and is especially prominent in domesticated plants, where artificial selection has favoured the same traits in many different species and varieties. The question of whether repeated evolution reflects changes at the same or different genes in each lineage can now be addressed using the domestication and improvement genes that have been identified in a variety of crops. Here, we document the genetic basis of nonpigmented ('white') pericarps in domesticated African rice (Oryza glaberrima) and compare it with the known genetic basis of the same trait in domesticated Asian rice (Oryza sativa). In some cases, white pericarps in African rice are apparently caused by unique mutations at the Rc gene, which also controls pericarp colour variation in Asian rice. In one case, white pericarps appear to reflect changes at a different gene or potentially a cis-regulatory region.