OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.

Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. Methods: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. Results: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. Conclusions: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. (JINS, 2019, 25, 204–214)

Microscopic and textural observations were made on ice samples cored from Blue Glacier slightly below the equilibrium line to depths of 60 m. Observations were started within a few minutes after collection. Water was found in veins along three-grain intersections, in lenses on grain boundaries and in irregular shapes. Gas was found in bubbles in the interior of crystals, in bubbles touching veins, and locally in veins. Vein sizes showed some spread; average cross-sectional area was about 7 × 10−4 mm2 with no discernible, trend with texture or depth except within 7 m of the surface. Before the samples were examined they could have experienced a complex relaxation which could have changed them significantly. As a result it is not possible to determine the in situ size of veins, but an upper limit can be determined. Also it is not possible to predict intergranular water flux per unit area, but 1 × 10−1 m a−1 represents an upper limit. In coarse-grained ice the water flux density is likely to be even smaller, because of a low density of veins, and blocking by bubbles. This indicates that only a very small fraction of the melt-water production on a typical summer day can penetrate into the glacier on an intergranular scale except possibly near the surface. The existence of conduit-like features in several cores suggests that much melt water can nevertheless penetrate the ice locally without large-scale lateral movements along the glacier surface. The observed profile of ice temperature indicates that the intergranular water flux may be much smaller than the upper limit determined from the core samples.

Six snow-pit records recovered from Siple Dome, West Antarctica, during 1994 are used to study seasonal variations in chemical (major ion and H202), isotopic (deuterium) and physical stratigraphic properties during the 1988-94 period. Comparison of δD measurements and satellite-derived brightness temperature for the Siple Dome area suggests that most seasonal SD maxima occur within ±4 weeks of each 1 January. Several other chemical species (H2O2, non-sea-salt (nss) SO4 2-, methanesulfonic acid and NO3-) show coeval peaks with SD, together providing an accurate method for identifying summer accumulation. Sea-salt-derived species generally peak during winter/spring, but episodic input is noted throughout some years. No reliable seasonal signal is identified in species with continental sources (nssCa2+ nss Mg2+), NH4+ or nssCl-. Visible strata such as large depth-hoar layers (>5 cm) are associated with summer accumulation and its metamorphosis, but smaller hoar layers and crusts are more difficult to interpret. A multi-parameter approach is found to provide the most accurate dating of these snow-pit records, and is used to determine annual layer thicknesses at each site Significant spatial accumulation variability exists on an annual basis, but mean accumulation in the sampled 10 km2 grid for the 1988-94 period is fairly uniform.

One of the questions still unanswered concerning the surge behavior of glaciers concerns their quasi-periodic occurrence. Some results on the phenomenological connection between local cumulative balance and surge initiation of Variegated Glacier, Alaska, U.S.A., are discussed here. Based on climate data from neighboring weather stations, an empirical relation between precipitation, temperature and local mass balance is established and used to reconstruct the annual balance at a location in the accumulation area back to 1905. Between the last four surges in 1946/47, 1964/65, 1982/83 and 1994/95, the ice-equivalent cumulative balance was 43.5 m on average, with a 1σ error of 1.2 m. Although the existence of a surge level cannot be directly interpreted in physical terms, it explains the variable length of the quiescent periods of Variegated Glacier by variations in the accumulation rate prior to the surge. We use the surge level to hindcast former unobserved surges, to compare the results with other surge datings obtained from photographs and to establish a complete surge history for Variegated Glacier for the 20th century.

The spatial distribution of accumulation across Siple Dome, West Antarctica, is determined from analysis of the shapes of internal layers detected by radio-echo sounding (RES) measurements. A range of assumed accumulation patterns is used in an ice-flow model to calculate a set of internal layer patterns. Inverse techniques are used to determine which assumed accumulation pattern produces a calculated internal layer pattern that best matches the shape of internal layers from RES measurements. All of the observed internal layer shapes at Siple Dome can be matched using a spatially asymmetric accumulation pattern which has been steady over time. Relative to the divide, the best-fitting accumulation pattern predicts 40% less accumulation 30 km from the divide on the south flank of Siple Dome and 15–40% more accumulation 30 km from the divide on the north flank. The data also allow the possibility for a small time variation of the pattern north of the divide. The mismatch between the calculated and the observed layer shapes is slightly reduced when the accumulation rate north of the divide is higher in the past (> 5kyr BP) than at present. Sensitivity tests show that the predicted change in the spatial accumulation pattern required to cause the slight Siple Dome divide migration (inferred from previous studies) would be detectable in the internal layer pattern if it persisted for > 2 kyr. Our analysis reveals no evidence that such a change has occurred, and the possible change in accumulation distribution allowed by the data is in the opposite sense. Therefore, it is unlikely that the Siple Dome divide migration has been caused by a temporal change in the spatial pattern of accumulation. This conclusion suggests the migration may be caused by elevation changes in Ice Streams C and D at the boundaries of Siple Dome.

Measurements of the surface and internal layer geometry from ice-penetrating radar and global positioning system surveys on three inter-ice-stream ridges in West Antarctica (Siple Dome, ridge DE and ridge BC) are examined with ice-flow models to infer (1) the history of the divide position at each site and (2) the spatial pattern of accumulation across the ridges. We find that the divide position is most steady at Siple Dome, somewhat steady at ridge DE and highly variable at ridge BC. Data from Siple Dome and ridge DE show evidence for steady northward motion of the ice divide for the past few thousand years. The layers beneath ridge BC suggest a 5 km northward shift of the divide position within the past several hundred years. Assuming the divide shifts are all due to changing elevation of the bounding ice streams, we infer the relative elevation history for segments of Ice Streams B–E. The northward displacement of the divide for all ridges implies a progressive relative thinning of the ice streams from E to B, with most dramatic recent thinning (100 m in <103 years) of Ice Stream B relative to Ice Stream C. Analysis of the internal layer pattern across the ridges indicates a south–north accumulation gradient with higher accumulation rates on the northern flanks of the ridges in all three cases. The inferred accumulation distribution is nearly uniform on the northern flanks, decreases sharply within a few ice thicknesses across the divides, and then decreases gradually farther to the south. The north/south decrease is strongest for ridge DE and weakest for ridge BC. This spatial pattern and the reduction in gradient strength with distance from the Amundsen Sea is consistent with the hypothesis that storms from the Amundsen Sea carry moisture first south then west over West Antarctica and deposit more snow on the windward side of ridges due to orographic lifting. This pattern has been stable for at least the past several thousand years.

Analysis of the cross-flow transmission of force from the central parts of a well-lubricated ice stream to its margins shows that there is a corresponding shift in the lateral location of motion-induced heat generation. The rate of basal heat generation in the center can be substantially smaller than the local rate of potential energy loss given by driving stress times the speed of downslope motion. The basal heating is a maximum for an intermediate level of lubrication for which speed is about 40% of the speed over a friction-less bed and base stress is about 25% of the driving stress. Stable and unstable balances between meltwater production and drainage on the bed are identified. A stable steady state with a speed less (more) than that giving maximum heat generation is termed drainage-(production-) limited, since an increase in speed would lead to increased (decreased) basal melting and must (need not) be balanced by increased drainage. It is shown that gradual evolution of the basal water drainage system and the factors affecting basal melting can cause discontinuous jumps between fast- and slow-moving states. A simplified analysis applied to six cross-sections of West Antarctic Ice Streams B, D, E and Rutford Ice Stream shows them to be diverse in the level of support from the sides and corresponding shift of mechanical heating sideward from their central parts. The cross-sections of Ice Stream B near “Upstream B” may be production-limited, because of especially high lubrication and related support from the sides. Cross-sections in the upper part of Ice Stream D, Ice Stream E and Rutford Ice Stream are in a drainage-limited condition. Substantial reduction of basal heat generation by side drag (in most cases) and expected high heat flow into the basal ice associated with low thickness (in some cases) tends to favor basal freezing. Nevertheless, all of the examined cross-sections except one are expected to experience basal melting with a modest geothermal heat-flux density of 60 m W m−1 or less in some cases. The lower part of Ice Stream B is an exception, where the analysis indicates that geothermal flux density must exceed 80–100 m W−1 m to maintain melting. If this high geothermal flux is not present, then the base of the lower part of Ice Stream B may be freezing, which would suggest continued deceleration of this part of Ice Stream B.

We have used ground-based radio-echo sounding (RES) profiles to reveal the spatial distribution of basal and internal ice properties across Siple Dome, West Antarctica, and under the dormant ice streams on its flanks. The RES-detected bed-reflection power, corrected for the effects of instrumentation and ice-thickness variation, is nearly constant across Siple Dome at a value suggesting spatially homogeneous basal properties of ice frozen to bedrock. Till, if present under the dome, must be thin (<0.1 m). The high basal reflectivity measured under now dormant “Siple Ice Stream” (SIS) and Ice Stream C suggests that they are underlain by either a thin (<0.05 m) water layer or a thick (>1 m) thawed or frozen till layer. The evidence that the dormant SIS is not frozen directly to underlying bedrock (but is separated by a water or till layer) is a further indication that it was once an active ice stream, and suggests that streaming motion may have ceased before the basal layer was frozen. The absence of a thick till layer beneath Siple Dome is consistent with its apparent stability as an inter-ice-stream ridge in the past and may suggest that it will remain as a stable limitation of ice-stream width in the future.

We present results from satellite imagery, ice-motion surveys and ice-penetrating radar studies of part of the north margin of Ice Stream C, one of the ice streams draining the West Antarctic ice sheet to the “Ross Embayment”. Our studies suggest that the shutdown of Ice Stream C about 150 years ago was not a single event, but a sequence involving stagnation of ice and migration of the ice-stream boundary. Ground-based studies confirm the inference from imagery that a series of former shear zones exist, decreasing in age towards the ice-stream center. A region of ice-stream trunk, including a former margin, lies sheared and folded between the (recent) inner and (older) outer margins of the area. ice-motion and topographic surveys give some constraint on the time of shutdown of the outer margin. The results provide a forum for discussing shutdown mechanisms. Possible causes for the stepwise migration of the north margin of Ice Stream C include a gradual decrease in ice flux, a reduction in the available water or hydrostatic pressure in the basal till, or a freezing of the till layers on the northern side.

Measurement of geometry, motion, and mass balance from Variegated Glacier, Alaska portray conditions in this surge-type glacier close to the mid-point of its 20 year surge cycle. Comparison of longitudinal profiles of ice depth, surface slope, and surface speed indicate that the motion occurs largely by internal deformation assuming the ice deforms according to the experimental law of Glen. Surface speed is not noticeably affected by local surface slope on the scale of the ice thickness or smaller, but correlates well with slope determined on a longitudinal averaging scale about one order of magnitude larger than the ice depth. The rate of motion on Variegated Glacier agrees well with rates on non-surge type temperate glaciers which have similar depth and slope. Although the (low regime at the time of the measurements is apparently typical of temperate glaciers, a large discrepancy between the balance flux needed for steady state and the actual flux is indicative of a rapidly changing surface elevation profile and internal stress distribution.

Variegated Glacier is a surge-type glacier in the St Elias mountain range in Alaska. The interval between surges is about 20 years; the last one occurred in 1964 to 1965. This glacier has been studied extensively since 1973 (Bindschadler and others, 1977). Thus far, measurements of ice velocities have been restricted to the surface. They have been analyzed using geophysically measured ice depths, in order to estimate ice velocities in the ice mass and at the base (Bindschadler and others, 1978). From 1973 to 1977 the distribution of annual ice velocities along most of the length of the glacier can be explained primarily by internal deformation without major contribution from sliding at the base. However, the variation of surface velocity with time gives definite indication that sliding occurs in summer and that the average summer rate is increasing progressively from summer to summer and that in a zone 5 to 7 km below the head of the glacier the summer-to-summer increase in inferred sliding rate is especially rapid. This is a notably distinguishing feature, which is probably indicative of a build-up toward the next surge. In order to obtain direct information about sliding-rates and water pressures at the base in this zone, a bore hole was drilled to the bottom of the glacier about 6 km below the glacier head. Observations in the hole started in June 1978 and were continued until 31 July 1978. The hole connected to an englacial water system at a depth of 204 m whereupon the water level dropped gradually to about 100 m below the surface. The last 6 m above-the base at 356 m could be drilled only by means of a cable tool because of the presence of debris-rich ice. Upon reaching the bottom, the water level increased rapidly to the firn water table at about 8 m below surface. Large variations in water level of about 200 m occurred during the following period of observation of 35 d. Major events such as audible icequakes, heavy rainfalls, and a period of unusually high ablation were associated with abrupt increases of water level up to the firn water table. High water pressure at the bottom drove a flow of muddy and sandy water upward in the hole. Consequently high freezing rates in the lower 150 m of the hole produced a very rough bore-hole wall covered with ledges, coral-reef-like features, grooves, and pockets filled with sand. Near the bottom, embedded rocks stuck out of the bore-hole wall. These features were recognized by bore-hole television. The bore-hole bottom consisted of sand which continuously proliferated and washed into the hole. Attempts to remove this sand by means of a sand pump failed, the bailed-out sand being replaced immediately. From bore-hole inclinometry an internal deformation of the ice mass of 0.22 m d−1 was obtained. Together with average surface velocity of 0.47 m d−1 we get a sliding velocity of 0.25 m d−1, averaged over the time of observation. This result confirms the sliding velocities inferred from surface velocity measurements. It also lies on the exponential trend line of increasing summer-to-summer velocities showing a doubling of sliding velocities about every two years (Bindschadler and others, unpublished). This strongly indicates that the next surge is likely to occur in the early eighties. Input of water from the surface probably will play a role in triggering the surge.