Two rather surprising anomalies relating to statistical power occur in testing mediation. First, in a model with no direct effect for which the total effect and indirect effect are identical, the ...power for the test of the total effect can be dramatically smaller than the power for the test of the indirect effect. Second, when there is a direct effect of a causal variable on the outcome controlling for the mediator, the power of the test of the indirect effect is often considerably greater than the power of the test of the direct effect, even when the two are of the same magnitude. We try to explain the reasons for these anomalies and how they affect practice.
This momentous work offers a groundbreaking history of the early civil rights movement in the South with new material that situates the book in the context of subsequent movement literature.
AbstractMicrobially induced calcite precipitation (MICP) is a promising biocementation process that can improve the geotechnical properties of granular soils through the precipitation of calcite. In ...this study, a large-scale biocementation experiment was completed to evaluate differences in improvement obtained using a bioaugmentation approach with S. pasteurii and a biostimulation approach, which stimulated native ureolytic microorganisms to complete the process. Two identical 1.7-m-diameter soil tank specimens containing a 0.3-m-thick layer of sand were treated using three wells at a well-to-well spacing of 1.2 m. Treatments were applied daily over 12 days and were designed to evaluate differences between tanks by creating a nonuniform spatial distribution of improvement. During treatment, shear wave velocity and biogeochemical changes were monitored spatially and temporally. Post-treatment, cone penetration tests were completed to assess improvement, and samples were obtained for calcite content measurements. Similar final improvement was observed between tanks, with highly cemented regions achieving shear wave velocities over 960 m/s and increases in tip resistances of over 419%. Results suggest that biostimulation may enable comparable biocementation improvement at the meter scale.
The International Immune Tolerance Study was a multicenter, prospective, randomized comparison of high-dose (HD; 200 IU/kg/d) and low-dose (LD; 50 IU/kg 3 times/week) factor VIII regimens in 115 ...“good-risk,” severe high-titer inhibitor hemophilia A subjects. Sixty-six of 115 subjects reached the defined study end points: success, n = 46 (69.7%); partial response, n = 3 (4.5%); and failure, n = 17 (25.8%). Successes did not differ between treatment arms (24 of 58 LD vs 22/57 HD, P = .909). The times taken to achieve a negative titer (P = .027), a normal recovery (P = .002), and tolerance (P = .116, nonsignificant) were shorter with the HD immune tolerance induction (ITI). Peak historical (P = .026) and on-ITI (P = .002) titers were correlated inversely with success, but only peak titer on ITI predicted outcome in a multivariate analysis (P = .002). LD subjects bled more often (odds ratio, 2.2; P = .0019). The early bleed rate/month was 0.62 (LD) and 0.28 (HD; P = .000 24), decreasing by 90% once negative titers were achieved. Bleeding was absent in 8 of 58 LD versus 21 of 57 HD subjects (P = .0085). One hundred twenty-four central catheter infections were reported in 41 subjects (19 LD); infection frequency did not differ between the treatment arms. Neither bleeding nor infection influenced outcome. Although it was stopped early for futility and safety considerations, this trial contributed valuable data toward evidence-based ITI practice.
Research focused on the analysis and classification of breast tumors, primarily using DNA microarrays and patterns of gene expression, has resulted in distinct tumor subtypes. Although no knowledge ...of patient survival or outcomes was used to derive these gene descriptions, these different classes based upon patterns of gene expression have important prognostic implications. Predictive markers in estrogen receptor–negative and triple‐negative disease will be particularly important because in the absence of therapy, these tumor subtypes tend to have a poor prognosis. In addition, the claudin‐low subgroup has been found to be common within the triple‐negative cancers and may have further prognostic and therapeutic implications. Patients with triple‐negative breast cancer do benefit from chemotherapy, but better treatment options are needed that are less toxic, reduce the risk of disease progression, and are more targeted to this patient population. Potential treatments include poly (ADP‐ribose) polymerase inhibitors, and therapies that target cancer stem cells could also have an important impact in these patients. This article will focus on the molecular stratification of triple‐negative breast cancers and the therapeutic implications of these classifications.
This article focuses on the molecular stratification of triple‐negative breast cancers and the therapeutic implications of these classifications.
Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory ...and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.
Background
Extensive reviews on the role of scaling and root planing (SRP) in the treatment of periodontitis have been previously published. This commentary will address the importance of subgingival ...calculus in the progression and treatment of periodontitis and addresses factors that make the execution of a “definitive” SRP a critical part of therapy.
Methods
A search for articles, using keywords relevant to the subject , (e.g., periodontitis, dental scaling, root planing, dental calculus, biofilm, inflammation) was conducted using PubMed, Ovid Medline, Cochrane Reviews and the ADA Center for Evidence Based Dentistry data bases. Additionally, references cited in relevant articles were also considered.
Results
Surfaces of subgingival calculus are covered with a biofilm of metabolically active bacteria. Periodontal inflammation is clearly related to the presence of calculus and biofilm. The primary goal of SRP is removal of subgingival calculus and biofilm deposits to create a biologically compatible root surface and reduce the inflammatory burden. Current evidence suggests that inflammation associated with periodontal infections affects both the immediate oral environment and the patient's systemic health.
Conclusion
SRP is still critical to the treatment of periodontitis. SRP involving deep probing depths (≥ 5 mm) and root surfaces with anatomical and surface irregularities, regardless of the type of instrumentation, requires time, exceptional skill and perseverance, and patient compliance with periodontal maintenance. Sites with persistent nonresponding probing depths and signs of inflammation following a definitive SRP, should be considered for surgical intervention.
Age-related hearing loss arises from irreversible damage in the inner ear, where sound is transduced into electrical signals. Prior human studies suggested that sensory-cell loss is rarely the cause; ...correspondingly, animal work has implicated the stria vascularis, the cellular "battery" driving the amplification of sound by hair cell "motors." Here, quantitative microscopic analysis of hair cells, auditory nerve fibers, and strial tissues in 120 human inner ears obtained at autopsy, most of whom had recent audiograms in their medical records, shows that the degree of hearing loss is well predicted from the amount of hair cell loss and that inclusion of strial damage does not improve the prediction. Although many aging ears showed significant strial degeneration throughout the cochlea, our statistical models suggest that, by the time strial tissues are lost, hair cell death is so extensive that the loss of battery is no longer important to pure-tone thresholds and that audiogram slope is not diagnostic for strial degeneration. These data comprise the first quantitative survey of hair cell death in normal-aging human cochleas, and reveal unexpectedly severe hair cell loss in low-frequency cochlear regions, and dramatically greater loss in high-frequency regions than seen in any aging animal model. Comparison of normal-aging ears to an age-matched group with acoustic-overexposure history suggests that a lifetime of acoustic overexposure is to blame.
This report upends dogma about the causes of age-related hearing loss. Our analysis of over 120 autopsy specimens shows that inner-ear sensory cell loss can largely explain the audiometric patterns in aging, with minimal contribution from the stria vascularis, the "battery" that powers the inner ear, previously viewed as the major locus of age-related hearing dysfunction. Predicting inner ear damage from the audiogram is critical, now that clinical trials of therapeutics designed to regrow hair cells are underway. Our data also show that hair cell degeneration in aging humans is dramatically worse than that in aging animals, suggesting that the high-frequency hearing losses that define human presbycusis reflect avoidable contributions of chronic ear abuse to which aging animals are not exposed.
Hepatitis C virus, a major human pathogen, produces infectious virus particles with several unique features, such as an ability to interact with serum lipoproteins, a dizzyingly complicated process ...of virus entry, and a pathway of virus assembly and release that is closely linked to lipoprotein secretion. Here, we review these unique features, with an emphasis on recent discoveries concerning virus particle structure, virus entry and virus particle assembly and release.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to evaluate the safety of raw vegetable products present on the German market regarding toxin-producing Bacillus cereus sensu lato (s.l.) group bacteria.
A total of 147 B. cereus ...s.l. group strains isolated from cucumbers, carrots, herbs, salad leaves and ready-to-eat mixed salad leaves were analyzed. Their toxinogenic potential was assessed by multiplex PCR targeting the hemolysin BL (hbl) component D (hblD), non-hemolytic enterotoxin (nhe) component A (nheA), cytotoxin K-2 (cytK-2) and the cereulide (ces) toxin genes. In addition, a serological test was used to detect Hbl and Nhe toxins. On the basis of PCR and serological results, none of the strains were positive for the cereulide protein/genes, while 91.2, 83.0 and 37.4% were positive for the Hbl, Nhe and CytK toxins or their genes, respectively. Numerous strains produced multiple toxins. Generally, strains showed resistance against the β-lactam antibiotics such as penicillin G and cefotaxim (100%), as well as amoxicillin/clavulanic acid combination and ampicillin (99.3%). Most strains were susceptible to ciprofloxacin (99.3%), chloramphenicol (98.6%), amikacin (98.0%), imipenem (93.9%), erythromycin (91.8%), gentamicin (88.4%), tetracycline (76.2%) and trimethoprim/sulfamethoxazole combination (52.4%). The genomes of eight selected strains were sequenced. The toxin gene profiles detected by PCR and serological test mostly agreed with those from whole-genome sequence data.
Our study showed that B. cereus s.l. strains encoding toxin genes occur in products sold on the German market and that these may pose a health risk to the consumer if present at elevated levels. Furthermore, a small percentage of these strains harbor antibiotic resistance genes. The presence of these bacteria in fresh produce should, therefore, be monitored to guarantee their safety.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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