Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015–2016

Background

Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65?years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65?years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults.

Amphitheater-headed canyons formed by megaflooding at Malad Gorge,Idaho

Many bedrock canyons on Earth and Mars were eroded by upstream propagating headwalls, and a prominent goal in geomorphology and planetary science is to determine formation processes from canyon morphology. A diagnostic link between process and form remains highly controversial, however, and field investigations that isolate controls on canyon morphology are needed. Here we investigate the origin of Malad Gorge, Idaho, a canyon system cut into basalt with three remarkably distinct heads: two with amphitheater headwalls and the third housing the active Wood River and ending in a 7% grade knickzone. Scoured rims of the headwalls, relict plunge pools, sediment-transport constraints, and cosmogenic (³He) exposure ages indicate formation of the amphitheater-headed canyons by large-scale flooding ∼46 ka, coeval with formation of Box Canyon 18 km to the south as well as the eruption of McKinney Butte Basalt, suggesting widespread canyon formation following lava-flow diversion of the paleo-Wood River. Exposure ages within the knickzone-headed canyon indicate progressive upstream younging of strath terraces and a knickzone propagation rate of 2.5 cm/y over at least the past 33 ka. Results point to a potential diagnostic link between vertical amphitheater headwalls in basalt and rapid erosion during megaflooding due to the onset of block toppling, rather than previous interpretations of seepage erosion, with implications for quantifying the early hydrosphere of Mars.Landscapes adjust to perturbations in tectonics and base level through upstream propagation of steepened river reaches, or knickzones, thereby communicating environmental signals throughout a drainage basin (e.g., ref. 1). Nowhere are knickzones more important and apparent than in landscapes where canyon heads actively cut into plateaus, such as tributaries of the Grand Canyon, United States, and the basaltic plains of Mars (e.g., refs. 2–4). Here the stark topographic contrast between low-relief uplands and deeply incised canyons sharply delineates canyon rims and planform morphology. Canyon heads can have varied shapes from amphitheaters with vertical headwalls to more pointed planform shapes with lower gradients, and a prominent goal in geomorphology and planetary science is to link canyon morphology to formation processes (e.g., refs. 4–8), with implications for understanding the history of water on Mars.Amphitheater-headed canyons on Mars are most likely cut into layered basalt (9, 10), and canyon-formation interpretations have ranged widely from slow seepage erosion to catastrophic megafloods (4–6, 11, 12). Few studies have been conducted on the formation of amphitheater-headed canyons in basalt on Earth, however, and instead, terrestrial canyons in other substrates are often used as Martian analogs. For example, groundwater sapping is a key process in forming amphitheater-headed canyons in unconsolidated sand (e.g., refs. 8, 13, 14), but its importance is controversial in rock (5, 12, 15). Amphitheater-headed canyons are also common to plateaus with strong-over-weak sedimentary rocks (3, 16); however, here the tendency for undercutting is so strong that canyon-head morphology may bear little information about erosional processes, whether driven by groundwater or overland flow (e.g., refs. 3, 5, 17). Canyons in some basaltic landscapes lack strong-over-weak stratigraphy, contain large boulders that require transport, and show potential for headwall retreat by block toppling (18–21), all of which make extension of process–form relationships in sand and sedimentary rocks to basalt and Mars uncertain.To test the hypothesis of a link between canyon formation and canyon morphology in basalt, we need field measurements that can constrain formation processes for canyons with distinct morphologies, but carved into the same rock type. Here we report on the origin of Malad Gorge, a canyon complex eroded into columnar basalt with markedly different shaped canyon heads. Results point to a potential diagnostic link between canyon-head morphology and formative process by megaflood erosion in basalt.Malad Gorge is a tributary to the Snake River Canyon, Idaho, within the Snake River Plain, a broad depression filled by volcanic flows that erupted between ∼15 Ma and ∼2 ka (22, 23). The gorge sits at the northern extent of Hagerman Valley, a particularly wide (∼7 km) part of the Snake River Canyon (Fig. 1). Malad Gorge is eroded into the Gooding Butte Basalt [⁴⁰Ar/³⁹Ar eruption age: 373 ± 12 ka (25)] which is composed of stacked lava beds, each several meters thick with similar well-defined columns bounded by cooling joints and no apparent differences in strength between beds. The Wood (or Malad) River, a major drainage system from the Sawtooth Range to the north, drains through Malad Gorge before joining the Snake River. The Wood River is thought to have been diverted from an ancestral, now pillow lava-filled canyon into Malad Gorge by McKinney Butte basalt flows (24) [⁴⁰Ar/³⁹Ar eruption age: 52 ± 24 ka (25) (Fig. 1).Open in a separate windowFig. 1.Shaded relief map of the study region (50-m contour interval) showing basalt flows (23), their exposure age sample locations, and the path of the ancestral Wood River following Malde (24) (US Geological Survey).Malad Gorge contains three distinct canyon heads herein referred to as Woody’s Cove, Stubby Canyon, and Pointed Canyon (Fig. 2A). Woody’s Cove and Stubby have amphitheater heads with ∼50-m-high vertical headwalls (Fig. 2C), and talus accumulation at headwall bases indicates long-lived inactive fluvial transport (Fig. 3 A and B). Woody’s Cove, the shortest of the three canyons, lacks major spring flows and has minor, intermittent overland flow partially fed by irrigation runoff that spills over the canyon rim. Stubby has no modern-day overland flow entering the canyon, and springs emanate from a pool near its headwall (Fig. 3B). In contrast, Pointed Canyon is distinctly more acute in planform morphology, contains a 7% grade knickzone composed of multiple steps rather than a vertical headwall (Figs. 2C and ​and3C),3C), and extends the farthest upstream.Open in a separate windowFig. 2.Malad Gorge topography (10-m contour interval) and aerial orthophotography (US Geological Survey). (A) Overview map and (B) close-up for Stubby and Pointed canyons showing mapped bedrock scours (white arrows), exposure age sample locations (red circles) with age results, location of the uppermost active knickpoint (black circle), abandoned bedrock channels (blue dashed lines), and grain-size analysis sites (blue squares). The blue star shows the reconstructed location of the headwall of Pointed Canyon at 46 ka (see Discussion and Fig. 5). (C) Longitudinal profile along Stubby and Pointed canyons from their confluence (shown as white lines in B) with local slope, S, averaged over regions demarked by dashed lines (Fig. 4A shows close-up of profile in Stubby Canyon).Open in a separate windowFig. 3.Photographs of (A) headwall of Woody’s Cove (person for scale, circled), (B) ∼50-m-high headwall of Stubby Canyon, (C) downstream-most waterfall at Pointed Canyon knickzone (12-m-high waterfall with overcrossing highway for scale), (D) fluted and polished notch at the rim of Stubby Canyon (notch relief is 10 m), (E) upstream-most waterfall at Pointed Canyon knickzone (within the southern anabranch of Fig. S2), and (F) upstream-most abandoned channel in Fig. 2B and Fig. S2 (channel relief is ∼10 m). White coloring on the headwalls in A and B is likely residue from irrigation runoff.Early work attributed the amphitheater-headed canyons in this region—Malad Gorge, Box Canyon, located 18 km south of Malad Gorge (Fig. 1), and Blue Lakes Canyon located 42 km to the SE—to formation by seepage erosion because of no modern overland flow and the occurrence of some of the largest springs in the United States in this region (7). Because spring flows (e.g., ∼10 m³/s in Box Canyon; US Geological Survey gauge 13095500) are far deficient to move the boulders that line the canyon floors, Stearns (7) reasoned that the boulders must chemically erode in place. This explanation is improbable, however, given the young age of the Quaternary basalt (25), spring water saturated in dissolved solids (19), and no evidence of rapid chemical weathering (e.g., talus blocks are angular and have little to no weathering rinds). Instead of groundwater sapping, Box Canyon was likely carved by a large-scale flood event that occurred ∼45 ka based on ³He cosmogenic exposure age dating of the scoured rim of the canyon headwall (19, 26). In addition, Blue Lakes Canyon was formed during the Bonneville Flood [∼18–22 ka (27, 28)], one of the world’s largest outburst floods that occurred as a result of catastrophic draining of glacial lake Bonneville (21). In both cases, canyon formation was inferred to have occurred through upstream headwall propagation by waterfall erosion.Herein we aim to test whether the amphitheater-headed canyons at Malad Gorge also owe their origin to catastrophic flooding, whether Pointed Canyon has a different origin, and whether canyon morphology is diagnostic of formation process. To this end we present field observations, sediment-size measurements, hydraulic modeling, and cosmogenic exposure ages of water-scoured rock surfaces and basalt-flow surfaces (Methods and Tables S1 and S2).     

FKS Mutations and Elevated Echinocandin MIC Values among Candida glabrata Isolates from U.S. Population-Based Surveillance

Candida glabrata is the second leading cause of candidemia in the United States. Its high-level resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance study for elevated echinocandin MIC values (MICs of ≥0.25 μg/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) for one or more of the echinocandin drugs caspofungin, anidulafungin, and micafungin. All of the isolates with elevated MIC values had a mutation in the previously identified hot spot 1 of either the glucan synthase FKS1 (n = 2) or FKS2 (n = 14) gene. No mutations were detected in hot spot 2 of either FKS1 or FKS2. The predominant mutation was mutation of FKS2-encoded serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G for FKS1 and R665G for FKS2, have not been reported previously for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.The most recent class of antifungal agents to be introduced into clinical practice for the treatment of Candida infections is the echinocandins (4). All three echinocandin antifungal drugs, caspofungin, micafungin, and anidulafungin, have been shown to be effective in treating both invasive and esophageal candidiases caused by most Candida species, including those refractory to azole therapy (6, 10, 27, 38). When the initial breakpoints for the echinocandin drugs were proposed by the Clinical and Laboratory Standards Institute (CLSI), no breakpoint for resistance was set because in the original clinical outcome trials there were too few isolates with elevated MICs for any of the echinocandins to make a judgment (31). Since then, there has been an increasing number of case reports of clinical failure of echinocandins in patients from whom Candida isolates with elevated MICs for the echinocandins have been recovered (reviewed in reference 34).Decreased susceptibility to the echinocandins is associated with mutations in the Fks1p and Fks2p subunits of the 1,3-β-d-glucan synthase complex, which is necessary for the production of 1,3-β-d-glucan, an essential component of the Candida cell wall (11, 12, 16, 25). Specifically, the mutations occur in two regions, of nine and eight amino acids, designated hot spot 1 and hot spot 2, respectively, that appear in both Fks1p and Fks2p (25). These mutations in the FKS1 and FKS2 genes result in the inability of echinocandins to inhibit the production of 1,3-β-d-glucan (26).Candida glabrata has recently emerged as the second most common cause of candidemia in the United States (29, 37). C. glabrata has demonstrated decreased susceptibility to azole drugs, especially fluconazole (32). This reduced susceptibility to azoles has led to the recommendation by the Infectious Diseases Society of America (IDSA) for the preferred use of an echinocandin as primary therapy for treatment of C. glabrata infections (24, 29). While there has been largely excellent coverage of C. glabrata by the echinocandins, as measured in vitro (13, 28, 31), there are cases of clinical failure of echinocandins against C. glabrata isolates (7, 14, 19, 36). To date, there has not been an epidemiological study which estimates the prevalence of C. glabrata isolates with elevated echinocandin MICs, and there is no clear picture of the relative frequency of these isolates at the population level.The Centers for Disease Control and Prevention (CDC) and selected Emerging Infections Program (EIP) partners conducted active population-based candidemia surveillance in the metropolitan areas of Atlanta, GA, and Baltimore, MD, between 2008 and 2010. Population-based surveillance is unique in that it includes the total population of a particular geographic area and avoids the biases associated with single or select institutional studies. Candida sp. bloodstream isolates from all hospitals within each defined geographic area were collected and identified to the species level. We used C. glabrata isolates collected in the population-based surveillance study to monitor MIC values for caspofungin, micafungin, and anidulafungin and to identify changes in the Fksp proteins associated with elevated echinocandin MIC values.     

Trends in emergent inguinal hernia surgery in Olmsted County, MN: a population-based study

Background

Evidence suggests that watchful waiting of inguinal hernias (IH) is safe because the risk of acute strangulation requiring an emergent repair is low. However, population-based incidence rates are lacking, and it is unknown whether the incidence of emergent inguinal hernia repairs (IHR) has changed over time.

Study design

A retrospective review of all IHR performed on adult residents of Olmsted County, Minnesota from 1989 to 2008 was performed using the Rochester epidemiology project, a record-linkage system that covers more than 97?% of the population (2010 US Census?=?146,466). Incidence rates/100,000 person-years were calculated, and trends over time were evaluated using Poisson regression.

Results

A total of 4,026 IHR were performed on 3,599 patients; 136 repairs (3.8?%) were emergent. Of these, 19 patients (14?%) had bowel resection and three (2?%) died within 30?days of the repair. Rates/100,000 person-years yielded an overall incidence of 7.6 for emergent IHR and 200.0 for elective IHR. Emergent IHR rates increased with age. Overall emergent IHR rates declined from 18.2 to 12.4 in men and from 6.4 to 2.4 in women from 1989 to 2008 (p?>?0.05). Older age, obesity, a high ASA risk score, a femoral and/or a recurrent hernia were more likely to be associated with an emergent IHR (all p?≤?0.05).

Conclusion

The incidence of emergent IHR is low. This risk has decreased over the past 20?years. However, patients who are either ≥70?years old, obese, with a high ASA score, or with a femoral or recurrent hernias are more likely to require an emergent IHR and could benefit from elective operative intervention if deemed adequate surgical candidates.     

Male breast cancer

Male breast cancer is rare, and many patients and health care providers are not familiar with this entity. Although the underlying causes are not well understood, certain populations are at higher risk, including certain gene mutation carriers, men with Klinefelter syndrome, and certain ethnic groups. Male breast cancer typically presents at a later stage than female breast cancer. A palpable mass is the most common presentation, but nipple discharge or other nipple changes may be seen. Because the number of affected individuals is small, prospective trials have not been conducted; thus, treatment recommendations are typically taken from large trials involving female breast cancer populations. Although outcomes in male breast cancer were previously thought to be worse than female breast cancer outcomes, it appears that they are similar. Questions regarding the most effective surgical and adjuvant therapies remain. Mastectomy with axillary lymph node evaluation, adjuvant hormonal therapy, and chemotherapy are commonly used. Providers of health care to male patients must be aware of the possibility of breast cancer and appropriately evaluate any suspicious changes.     

Lessons learned from an unusual case of inflammatory breast cancer

Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated with poor long-term outcomes despite aggressive surgical and chemotherapeutic interventions. We recently treated a 56-year-old woman with right-sided IBC and biopsy-proven cutaneous metastases to her back and left breast. She underwent chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One year after diagnosis, she is currently disease-free based on positron-emission tomography (PET) imaging and repeat skin biopsies. To provide insight into the management of IBC, we present this interesting case with a reflection on important lessons to be learned.     

Twenty Years of Active Bacterial Core Surveillance

Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.     

Influence of calcium permeabilization and membrane-attached hemoglobin on erythrocyte deformability.

The present study was designed to evaluate the influence of intracellular calcium [Ca]i regulated membrane attached hemoglobin (Hbm) on the deformability of human RBC and ghosts. [Ca]i of RBC was elevated via the ionophore A23187 (10 microM); the deformability of RBC and resealed ghosts was determined via measuring RBC and ghost transit times through 5 microns diameter pores with the Cell Transit Analyzer (CTA). Salient results included: (1) significantly increased RBC levels of Hbm following ionophore treatment; (2) elevated Hbm with increasing lysing medium calcium concentration (0-5 mM); (3) decreased deformability of both intact RBC and ghosts with increasing Hbm and significant (P less than 0.02 or better) linear relationships between Hbm and RBC or ghost transit times; and (4) an increased sensitivity to ionophore treatment/membrane attached hemoglobin for the higher percentiles of the CTA transit time distribution (i.e., for more rigid subpopulations). Our results thus indicate that calcium-induced interaction of hemoglobin with the RBC membrane produces cellular rheological changes; in addition, they demonstrate the usefulness of the CTA system in measuring both average RBC rheologic behavior and the distribution of cellular rheologic properties within an erythrocyte population.