Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

TEAM-UP for quality: a cluster randomized controlled trial protocol focused on preventing pressure ulcers through repositioning frequency and precipitating factors

Background: Pressure ulcers/injuries (PrUs), a critical concern for nursing homes (NH), are responsible for chronic wounds, amputations, septic infections, and premature deaths. PrUs occur most commonly in older adults and NH residence is a risk factor for their development, with at least one of every nine U.S. NH residents experiencing a PrU and many NHs having high incidence and prevalence rates, in some instances well over 20%. PrU direct treatment costs are greater than prevention costs, making prevention-focused protocols critical. Current PrU prevention protocols recommend repositioning residents at moderate, high, and severe risk every 2 h. The advent of visco- elastic (VE) high-density foam support-surfaces over the past decade may now make it possible to extend the repositioning interval to every 3 or 4 h without increasing PrU development. The TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study aims to determine: 1) whether repositioning interval can be extended for NH residents without compromising PrU incidence and 2) how changes in medical severity interact with changes in risk level and repositioning schedule to predict PrU development. Methods: In this proposed cluster randomized study, 9 NHs will be randomly assigned to one of three repositioning intervals (2, 3, or 4 h) for a 4-week period. Each enrolled site will use a single NH-wide repositioning interval as the standard of care for residents at low, moderate, and high risk of PrU development (N = 951) meeting the following criteria: minimum 3-day stay, without PrUs, no adhesive allergy, and using VE support surfaces (mattresses). An FDA-cleared patient monitoring system that records position/movement of these residents via individual wireless sensors will be used to visually cue staff when residents need repositioning and document compliance with repositioning protocols. Discussion: This study will advance knowledge about repositioning frequency and clinically assessed PrU risk level in relation to PrU incidence and medical severity. Outcomes of this research will contribute to future guidelines for more precise preventive nursing practices and refinement of PrU prevention guidelines. Trial registration: Clinical Trial Registration: NCT02996331

Minimally invasive scoliosis surgery: an innovative technique in patients with adolescent idiopathic scoliosis

Minimally invasive spine surgery is becoming more common in the treatment of adult lumbar degenerative disorders. Minimally invasive techniques have been utilized for multilevel pathology, including adult lumbar degenerative scoliosis. The next logical step is to apply minimally invasive surgical techniques to the treatment of adolescent idiopathic scoliosis (AIS). However, there are significant technical challenges of performing minimally invasive surgery on this patient population. For more than two years, we have been utilizing minimally invasive spine surgery techniques in patients with adolescent idiopathic scoliosis. We have developed the present technique to allow for utilization of all standard reduction maneuvers through three small midline skin incisions. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, and allows adequate facet osteotomy to enable fusion. There are multiple potential advantages of this technique, including: less blood loss, shorter hospital stay, earlier mobilization, and relatively less pain and need for pain medication. The operative time needed to complete this surgery is longer. We feel that a minimally invasive approach, although technically challenging, is a feasible option in patients with adolescent idiopathic scoliosis. Although there are multiple perceived benefits, long term data is needed before it can be recommended for routine use

Longitudinal multi-centre brain imaging studies: guidelines and practical tips for accurate and reproducible imaging endpoints and data sharing

Abstract Background Research involving brain imaging is important for understanding common brain diseases. Study endpoints can include features and measures derived from imaging modalities, providing a benchmark against which other phenotypical data can be assessed. In trials, imaging data provide objective evidence of beneficial and adverse outcomes. Multi-centre studies increase generalisability and statistical power. However, there is a lack of practical guidelines for the set-up and conduct of large neuroimaging studies. Methods We address this deficit by describing aspects of study design and other essential practical considerations that will help researchers avoid common pitfalls and data loss. Results The recommendations are grouped into seven categories: (1) planning, (2) defining the imaging endpoints, developing an imaging manual and managing the workflow, (3) performing a dummy run and testing the analysis methods, (4) acquiring the scans, (5) anonymising and transferring the data, (6) monitoring quality, and (7) using structured data and sharing data. Conclusions Implementing these steps will lead to valuable and usable data and help to avoid imaging data wastage

A Comparison of Administrative and Physiologic Predictive Models in Determining Risk Adjusted Mortality Rates in Critically Ill Patients

Hospitals are increasingly compared based on clinical outcomes adjusted for severity of illness. Multiple methods exist to adjust for differences between patients. The challenge for consumers of this information, both the public and healthcare providers, is interpreting differences in risk adjustment models particularly when models differ in their use of administrative and physiologic data. We set to examine how administrative and physiologic models compare to each when applied to critically ill patients.We prospectively abstracted variables for a physiologic and administrative model of mortality from two intensive care units in the United States. Predicted mortality was compared through the Pearsons Product coefficient and Bland-Altman analysis. A subgroup of patients admitted directly from the emergency department was analyzed to remove potential confounding changes in condition prior to ICU admission.We included 556 patients from two academic medical centers in this analysis. The administrative model and physiologic models predicted mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6% (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r(2) for these models was 0.297. The Bland-Atlman plot suggests that at low predicted mortality there was good agreement; however, as mortality increased the models diverged. Similar results were found when analyzing a subgroup of patients admitted directly from the emergency department. When comparing the two hospitals, there was a statistical difference when using the administrative model but not the physiologic model. Unexplained mortality, defined as those patients who died who had a predicted mortality less than 10%, was a rare event by either model.In conclusion, while it has been shown that administrative models provide estimates of mortality that are similar to physiologic models in non-critically ill patients with pneumonia, our results suggest this finding can not be applied globally to patients admitted to intensive care units. As patients and providers increasingly use publicly reported information in making health care decisions and referrals, it is critical that the provided information be understood. Our results suggest that severity of illness may influence the mortality index in administrative models. We suggest that when interpreting "report cards" or metrics, health care providers determine how the risk adjustment was made and compares to other risk adjustment models

Cyclophosphamide- metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study

Abstract Introduction Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. Methods We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. Results In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. Conclusions These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer

Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Background: Overweight is reported as a side effect of SDR. The aims were to study the development of weight, height and body mass index (BMI) during five years after SDR. Methods: This prospective, longitudinal and practice-based study included all 56 children with CP spastic diplegia undergoing SDR from the start in March 1993 to April 2003 in our hospital. The preoperative Gross Motor Function Classification System (GMFCS) levels were I-II in 17, III in 15, IV-V in 24 children. Median age at SDR was 4.3 years (range 2.4-7.4 years). Weight and height/recumbent length were measured. Swedish growth charts for typically developing children generated weight, height and BMI z-scores for age and gender. Results: The preoperative median z-scores were for height-1.92 and for body mass index (BMI)-0.22. Five years later, the median BMI z-score was increased by + 0.57 (p + 2 SD) increased (p < 0.05). Baseline BMI and age at the start of follow-up influenced the BMI change during the five years (p < 0.001 and p < 0.05 respectively). The individual growth was highly variable, but a tendency towards increasing stunting with age was seen in severe gross motor dysfunction (GMFCS levels IV-V) and the opposite, a slight catch-up of height in children with walking ability (GMFCS levels I-III). Conclusions: These are the first available subtype-and GMFCS-specific longitudinal growth data for children with CP spastic diplegia. Their growth potential according to these data should be regarded as a minimum, as some children were undernourished. It is unknown whether the spasticity reduction through SDR increased the weight gain velocity, or if the relative weight increase was part of the general "obesity epidemic". For some children the weight increase was highly desirable. In others, it resulted in overweight and obesity with risk of negative health effects. Weight and height should be monitored to enable early prevention of weight aberrations also causing problems with mobility, activity and participation