Neonatal enteral feeding tubes as loci for colonisation by members of the Enterobacteriaceae

Background The objective of this study was to determine whether neonatal nasogastric enteral feeding tubes are colonised by the opportunistic pathogen Cronobacter spp. (Enterobacter sakazakii) and other Enterobacteriaceae, and whether their presence was influenced by the feeding regime. Methods One hundred and twenty-nine tubes were collected from two neonatal intensive care units (NICU). A questionnaire on feeding regime was completed with each sample. Enterobacteriaceae present in the tubes were identified using conventional and molecular methods, and their antibiograms determined. Results The neonates were fed breast milk (16%), fortified breast milk (28%), ready to feed formula (20%), reconstituted powdered infant formula (PIF, 6%), or a mixture of these (21%). Eight percent of tubes were received from neonates who were 'nil by mouth'. Organisms were isolated from 76% of enteral feeding tubes as a biofilm (up to 107 cfu/tube from neonates fed fortified breast milk and reconstituted PIF) and in the residual lumen liquid (up to 107 Enterobacteriaceae cfu/ml, average volume 250 µl). The most common isolates were Enterobacter cancerogenus (41%), Serratia marcescens (36%), E. hormaechei (33%), Escherichia coli (29%), Klebsiella pneumoniae (25%), Raoultella terrigena (10%), and S. liquefaciens (12%). Other organisms isolated included C. sakazakii (2%),Yersinia enterocolitica (1%),Citrobacter freundii (1%), E. vulneris (1%), Pseudomonas fluorescens (1%), and P. luteola (1%). The enteral feeding tubes were in place between < 6 h (22%) to > 48 h (13%). All the S. marcescens isolates from the enteral feeding tubes were resistant to amoxicillin and co-amoxiclav. Of additional importance was that a quarter of E. hormaechei isolates were resistant to the 3rd generation cephalosporins ceftazidime and cefotaxime. During the period of the study, K. pneumoniae and S. marcescens caused infections in the two NICUs. Conclusion This study shows that neonatal enteral feeding tubes, irrespective of feeding regime, act as loci for the bacterial attachment and multiplication of numerous opportunistic pathogens within the Enterobacteriaceae family. Subsequently, these organisms will enter the stomach as a bolus with each feed. Therefore, enteral feeding tubes are an important risk factor to consider with respect to neonatal infections.

Variable time-scale information processing

With the extensive use of pulse modulation methods in telecommunications, much work has been done in the search for a better utilisation of the transmission channel.The present research is an extension of these investigations. A new modulation method, 'Variable Time-Scale Information Processing', (VTSIP), is proposed.The basic principles of this system have been established, and the main advantages and disadvantages investigated. With the proposed system, comparison circuits detect the instants at which the input signal voltage crosses predetermined amplitude levels.The time intervals between these occurrences are measured digitally and the results are temporarily stored, before being transmitted.After reception, an inverse process enables the original signal to be reconstituted.The advantage of this system is that the irregularities in the rate of information contained in the input signal are smoothed out before transmission, allowing the use of a smaller transmission bandwidth. A disadvantage of the system is the time delay necessarily introduced by the storage process.Another disadvantage is a type of distortion caused by the finite store capacity.A simulation of the system has been made using a standard speech signal, to make some assessment of this distortion. It is concluded that the new system should be an improvement on existing pulse transmission systems, allowing the use of a smaller transmission bandwidth, but introducing a time delay.

Stability studies on pencillin derivatives

Current analytical assay methods for ampicillin sodium and cloxacillin sodium are discussed and compared, High Performance Liquid Chromatography (H.P.L.C.) being chosen as the most accurate, specific and precise. New H.P.L.C. methods for the analysis of benzathine cloxacillin; benzathine penicillin V; procaine penicillin injection B.P.; benethamine penicillin injection; fortified B.P.C.; benzathine penicillin injection; benzathine penicillin injection, fortified B.P.C.; benzathine penicillin suspnsion; ampicillin syrups and penicillin syrups are described. Mechanical or chemical damage to column packings is often associated with H.P.L.C. analysis. One type, that of channel formation, is investigated. The high linear velocity of solvent and solvent pulsing during the pumping cycle were found to be the cause of this damage. The applicability of nonisotherrnal kinetic experiments to penicillin V preparations, including formulated paediatric syrups, is evaluated. A new type of nonisotherrnal analysis, based on slope estimation and using a 64K Random Access Memory (R.A.M.) microcomputer is described. The name of the program written for this analysis is NONISO. The distribution of active penicillin in granules for reconstitution into ampicillin and penicillin V syrups, and its effect on the stability of the reconstituted products, are investigated. Changing the diluent used to reconstitue the syrups was found to affect the stability of the product. Dissolution and stability of benzathine cloxacillin at pH2, pH6 and pH9 is described, with proposed dissolution mechanisms and kinetic analysis to support these mechanisms. Benzathine and cloxacillin were found to react in solution at pH9, producing an insoluble amide.

GPCR production in a novel yeast strain that makes cholesterol-like sterols

The activities of many mammalian membrane proteins including G-protein coupled receptors are cholesterol-dependent. Unlike higher eukaryotes, yeast do not make cholesterol. Rather they make a related molecule called ergosterol. As cholesterol and ergosterol are biologically non-equivalent, the potential of yeast as hosts for overproducing mammalian membrane proteins has never been fully realised. To address this problem, we are trying to engineer a novel strain of Saccharomyces cerevisiae in which the cholesterol biosynthetic pathway of mammalian cells has been fully reconstituted. Thus far, we have created a modified strain that makes cholesterol-like sterols which has an increased capacity to make G-protein coupled receptors compared to control yeast.

Innovating from the War Economy: Formal, Informal, and Illicit Economic Activities of the Military in Colombia

Over the last decade, the Colombian military has successfully rolled back insurgent groups, cleared and secured conflict zones, and enabled the extraction of oil and other key commodity exports. As a result, official policies of both the Uribe and Santos governments have promoted the armed forces to participate to an unprecedented extent in economic activities intended to consolidate the gains of the 2000s. These include formal involvement in the economy, streamlined in a consortium of military enterprises and social foundations that are intended to put the Colombian defense sector “on the map” nationally and internationally, and informal involvement expanded mainly through new civic action development projects intended to consolidate the security gains of the 2000s. However, failure to roll back paramilitary groups other than through the voluntary amnesty program of 2005 has facilitated the persistence of illicit collusion by military forces with reconstituted “neoparamilitary” drug trafficking groups. It is therefore crucially important to enhance oversight mechanisms and create substantial penalties for collusion with illegal armed groups. This is particularly important if Colombia intends to continue its new practice of exporting its security model to other countries in the region. The Santos government has initiated several promising reforms to enhance state capacity, institutional transparence, and accountability of public officials to the rule of law, which are crucial to locking in security gains and revitalizing democratic politics. Efforts to diminish opportunities for illicit association between the armed forces and criminal groups should complement that agenda, including the following: Champion breaking existing ties between the military and paramilitary successor groups through creative policies involving a mixture of punishments and rewards directed at the military; Investigation and extradition proceedings of drug traffickers, probe all possible ties, including as a matter of course the possibility of Colombian military collaboration. Doing so rigorously may have an important effect deterring military collusion with criminal groups. Establish and enforce zero-tolerance policies at all military ranks regarding collusion with criminal groups; Reward military units that are effective and also avoid corruption and criminal ties by providing them with enhanced resources and recognition; Rely on the military for civic action and development assistance as minimally as possible in order to build long-term civilian public sector capacity and to reduce opportunities for routine exposure of military forces to criminal groups circulating in local populations.

Microspheres for liver radiomicrospheres therapy and planning

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with 68Ga and/or 99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that 68Ga-PGCD, 68Ga-CHSg and 68Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; 99mTc-PGCD and 99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: 99mTc-CHSg and 68Ga-NOTA-CHSg. For the 99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the 99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with 90 Y for production of 90Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (99mTc-MAA for 68Ga-NOTA-CHSg and 99m Tc-CHSg; 90Y-SirTEX for 90Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.

Novel Purification of Archaeal Rnase P Protein, Pfu Rpp38, for Nmr Studies

Dr. Kenneth Murray, Ph.D. Assistant Professor of Biology Ribonuclease P (RNase P) is an essential and ubiquitous ribonucleoprotein enzyme primarily responsible for cleaving 5' leader sequences during tRNA maturation. RNase P comprises one essential RNA, and one protein subunit in eubacteria, five proteins in archaea, and ten in humans. Due to its homology to human RNase P, its higher stability, and simpler structure; extensive studies have been conducted utilizing the enzyme from the archaeal hyperthermophile, Pyrococcus furious (Pfu). Previous studies identified only four protein subunits associated with the archaeal RNase P. This fourprotein reconstituted particle, however, had an optimal temperature of 55°C, compared to the optimal 70°C of the wild type RNase P. Additional probing of the organism's genome database revealed a fifth RNase P protein subunit, RPP38. To facilitate further investigations of Pfu RNase complexes, we sought to develop a protocol for the purification ofRPP38. Our results, presented herein, represent the first known expression.purification protocol developed for RPP38. Briefly, we synthesized an N-terminal6x-His RPP38 fusion construct, reengineered to contain a Tobacco Etch Virus (TEV) protease cleavage site. Purification was achieved via immobilized metal affinity chromatography and reversed phase high performance liquid chromatography. Following purification the 6X-His affinity tag was removed via TEV cleavage, thus regenerating the native RPP38 protein. Purity and identity of RPP38 were confirmed by sodium dodecylsulfate - polyacrylamide gel electrophoresis and mass spectrometry, respectively. Our work is expected to contribute to our understanding ofRNase P function and tRNA maturation by providing an efficient, facile technique to express and purify Pfu RNase protein RPP38 as a means to facilitate structural and functional analyses.

Geochemistry of Southern Ocean sediments

Reconstructing past detrital flux and provenance in the Southern Ocean provides information about changes in source regions associated with climate variations and transport pathways. We present a Last Glacial Maximum (LGM) to Holocene comparison of 230Th normalised fluxes combined with sediment provenance data (Pb, Nd and Sr isotopes) from a latitudinal core transect in the eastern Atlantic sector of the Southern Ocean (ODP Leg 177 cores). We compare the radiogenic isotopic composition (IC) of detritus in these cores to that of cores proximal to potential source areas. We observe a well-defined latitudinal Holocene gradient in both detrital flux and provenance of sediment. High detrital fluxes in the north are associated with terrigenous material derived from southern Africa, while low detrital fluxes in the south are associated with supply from southern South America, West Antarctica and the South Sandwich Islands. The data suggest that this well-defined Holocene gradient in detrital flux and sediment provenance is controlled by the flow of the Antarctic Circumpolar Current (ACC) and the position of its frontal zones. The LGM is characterised by 2 to 6 times higher than modern detrital fluxes at most ODP Leg 177 sites. The LGM detrital fluxes do not show a latitudinal trend and suggest a greater supply of glaciogenic detritus sourced from southern South America. Glacial Patagonian outwash sediments (< 5 µm fraction) were analysed and compared to the bulk compositions of the marine sediments. The Pb IC of the Patagonian sediments is very similar to the glacial IC of sediments in the Scotia Sea and at ~ 49° S latitude in the eastern Atlantic sector. We propose that the glacial IC of sediments is controlled by increased delivery of Patagonian detritus initially supplied by glaciers and then transported at depth via the ACC.

Glacial North Atlantic: Sea surface conditions reconstructed by GLAMAP 2000

The response of the tropical ocean to global climate change and the extent of sea ice in the glacial nordic seas belong to the great controversies in paleoclimatology. Our new reconstruction of peak glacial sea surface temperatures (SSTs) in the Atlantic is based on census counts of planktic foraminifera, using the Maximum Similarity Technique Version 28 (SIMMAX-28) modern analog technique with 947 modern analog samples and 119 well-dated sediment cores. Our study compares two slightly different scenarios of the Last Glacial Maximum (LGM), the Environmental Processes of the Ice Age: Land, Oceans, Glaciers (EPILOG), and Glacial Atlantic Ocean Mapping (GLAMAP 2000) time slices. The comparison shows that the maximum LGM cooling in the Southern Hemisphere slightly preceeded that in the north. In both time slices sea ice was restricted to the north western margin of the nordic seas during glacial northern summer, while the central and eastern parts were ice-free. During northern glacial winter, sea ice advanced to the south of Iceland and Faeroe. In the central northern North Atlantic an anticyclonic gyre formed between 45° and 60°N, with a cool water mass centered west of Ireland, where glacial cooling reached a maximum of >12°C. In the subtropical ocean gyres the new reconstruction supports the glacial-to-interglacial stability of SST as shown by CLIMAP Project Members (CLIMAP) [1981]. The zonal belt of minimum SST seasonality between 2° and 6°N suggests that the LGM caloric equator occupied the same latitude as today. In contrast to the CLIMAP reconstruction, the glacial cooling of the tropical east Atlantic upwelling belt reached up to 6°-8°C during Northern Hemisphere summer. Differences between these SIMMAX-based and published U37[k]- and Mg/Ca-based equatorial SST records are ascribed to strong SST seasonalities and SST signals that were produced by different planktic species groups during different seasons.

Avaliação térmica e desempenho do processo de secagem de misturas de graviola e leite em secador de leito de jorro

The soursop (A. muricata) is a fruit rich in minerals especially the potassium content. The commercialization of soursop in natura and processed has increased greatly in recent years. Drying fruit pulp in order to obtain the powdered pulp has been studied, seeking alternatives to ensure the quality of dehydrated products at a low cost of production. The high concentration of sugars reducing present in fruits causes problems of agglomeration and retention during fruit pulp drying in spouted bed dryers. On the other hand in relation to drying of milk and fruit pulp with added milk in spouted bed, promising results are reported in the literature. Based on these results was studied in this work drying of the pulp soursop with added milk in spouted bed with inert particles. The tests were based on a 24 factorial design were evaluated for the effects of milk concentration (30 to 50% m/m), drying air temperature (70 to 90 °C), intermittency time (10 to 14 min), and ratio of air velocity in relation to the minimum spout (1.2 to 1.5) on the rate of production, of powder moisture, yield, rate of drying and thermal efficiency of the process. There were physical and chemical analysis of mixtures, of powders and of mixtures reconstituted by rehydration powders. Were adjusted statistical models of first order to data the rate of production, yield and thermal efficiency, that were statistically significant and predictive. An efficiency greater than 40% under the conditions of 50% milk mixture, at 70 ° C the drying air temperature and 1.5 for the ratio between the air velocity and the minimum spout has been reached. The intermittency time showed no significant effect on the analyzed variables. The final product had moisture in the range of 4.18% to 9.99% and water activity between 0.274 to 0.375. The mixtures reconstituted by rehydration powders maintained the same characteristics of natural blends.

Representações discursivas sobre lampião e seu bando em notícias de jornais mossoroenses (1927): “O mais audaz e miserável de todos os bandidos” e o seu “grupo de asseclas”

In this doctoral thesis analyzed the discursive representations of the bandit Lampião, the Lantern and his bandits gang in news mossoroenses newspapers published in the twenties of the last century (1927), when the gang invasion of the city of Mossoro in the state of Rio Grande do Norte, on June 13 of that year. To this end, we take as basis the theoretical assumptions of linguistics Textual, especially the narrower context of what is known today as Textual Analysis of the Discourses (ADT), theoretical and descriptive approach to linguistic studies of the text proposed by the French linguist Jean-Michel Adam. In this approach, we are interested in, specifically, the semantic level of the text, highlighting the notion of discursive representation, studied based on benchmarking operations, predication, modification, spatial location and temporal connection and analogy (ADAM, 2011; CASTILHO, 2010; KOCH, 2002, 2006; MARCUSCHI, 1998, 2008; NEVES, 2007; RODRIGUES, PASSEGGI & SILVA NETO, 2010). The corpus of this research consists of three reports in the twenties of the last century in newspapers The Mossoroense, Correio do Povo and the Northeast, and reconstituted through the collection held in the Municipal Museum Lauro Scotland files, Memorial Resistance Mossoro, both located in Natal, and in the news collection of Lampião newspapers in Natal, north of Rio Grande Raimundo Nonato historian. The discursive representations are built from the use of semantic analysis operations. Lampião to, the following representations are built: bandit, head of bandits, briber, defeated, Captain and Lord. To the outlaws of Lampião bunch of the following discursive representations were built: group, gang, gangsters, mates, bloodthirsty pack, brigands, bandits, criminals, burglar horde, and wild beasts. These representations reveal mainly the views of the newspapers of that time, which represented mainly the interests of traders, politicians, the government itself and generally Mossoró population.

Surface velocity fields, digital elevation models, ice front positions and grounding line derived from remote sensing data at Dinsmoor-Bombardier-Edgeworth glacier system, Antarctic Peninsula (1992-2014)

The northern Antarctic Peninsula is one of the fastest changing regions on Earth. The disintegration of the Larsen-A Ice Shelf in 1995 caused tributary glaciers to adjust by speeding up, surface lowering, and overall increased ice-mass discharge. In this study, we investigate the temporal variation of these changes at the Dinsmoor-Bombardier-Edgeworth glacier system by analyzing dense time series from various spaceborne and airborne Earth observation missions. Precollapse ice shelf conditions and subsequent adjustments through 2014 were covered. Our results show a response of the glacier system some months after the breakup, reaching maximum surface velocities at the glacier front of up to 8.8 m/d in 1999 and a subsequent decrease to ~1.5 m/d in 2014. Using a dense time series of interferometrically derived TanDEM-X digital elevation models and photogrammetric data, an exponential function was fitted for the decrease in surface elevation. Elevation changes in areas below 1000 m a.s.l. amounted to at least 130±15 m130±15 m between 1995 and 2014, with change rates of ~3.15 m/a between 2003 and 2008. Current change rates (2010-2014) are in the range of 1.7 m/a. Mass imbalances were computed with different scenarios of boundary conditions. The most plausible results amount to -40.7±3.9 Gt-40.7±3.9 Gt. The contribution to sea level rise was estimated to be 18.8±1.8 Gt18.8±1.8 Gt, corresponding to a 0.052±0.005 mm0.052±0.005 mm sea level equivalent, for the period 1995-2014. Our analysis and scenario considerations revealed that major uncertainties still exist due to insufficiently accurate ice-thickness information. The second largest uncertainty in the computations was the glacier surface mass balance, which is still poorly known. Our time series analysis facilitates an improved comparison with GRACE data and as input to modeling of glacio-isostatic uplift in this region. The study contributed to a better understanding of how glacier systems adjust to ice shelf disintegration.

Characterication of metals in hemolymph and tissues of the Antarctic bivalve Laternula elliptica

A high input of lithogenic sediment from glaciers was assumed to be responsible for high Fe and Mn contents in the Antarctic soft shell clam Laternula elliptica at King George Island. Indeed, withdrawal experiments indicated a strong influence of environmental Fe concentrations on Fe contents in bivalve hemolymph, but no significant differences in hemolymph and tissue concentrations were found among two sites of high and lower input of lithogenic debris. Comparing Fe and Mn concentrations of porewater, bottom water, and hemolymph from sampling sites, Mn appears to be assimilated as dissolved species, whereas Fe apparently precipitates as ferrihydrite within the oxic sediment or bottom water layer prior to assimilation by the bivalve. Hence, we attribute the high variability of Fe and Mn accumulation in tissues of L. elliptica around Antarctica to differences in the geochemical environment of the sediment and the resulting Fe and Mn flux across the benthic boundary.

Age determination of sediments off western Svalbard

Late Quaternary sediment yields from the Isfjorden drainage area (7327 km**2), a high arctic region on Svalbard characterized by an alpine landscape, have been reconstructed by using seismic stratigraphy supported by sediment core analysis. The sediments that accumulated in the fjord during and since deglaciation can be divided into three stratigraphic units. The volumes of these units were determined and converted into sediment yield rates averaged over the drainage basin. During deglaciation, 13 to 10 ka, the sediment yield was ~860 tons(t)/km**2/yr. In the early Holocene it decreased to 190 t/km**2/yr, and then increased to 390t/km**2/yr during the late Holocene Little Ice Age. When normalized to the approximate glacierized area, these rates correspond to a sediment yield of ~800 t/km**2/yr . Sediment yield from non-glacierized parts of the drainage is estimated to be 35 t/km**2/yr. At times when ice advanced to the shelf edge, sediment was scoured from the fjord and deposited on the outer shelf and in a well-defined deep sea fan. Between 200 ka and 13 ka, 328 km**3 of sediment accumulated here, corresponding to a mean sediment yield rate of 335 t/km**2/yr. This is broadly consistent with calculations based on the above rates of sediment yield in glacierized and non-glacierized areas, and on estimates, based on glacial geology, of the temporal variation in degree of glacierization over the past 200 kyr. These figures indicate that much of the glacigenic sediment on the shelf and slope was eroded from the uplands of Svalbard by small glaciers during interstadials and interglacials. The sediments were temporarily stored in the fjord prior to redeposition on the shelf and slope during ice sheet advance. Taken into consideration, such redisposition of pre-eroded material will reduce estimates of primary ice sheet erosion rate.

Last glacial maximum sediment record of the southern Weddell Sea shelf

Abstract: The history of grounded ice-sheet extent on the southern Weddell Sea shelf during the Last Glacial Maximum (LGM) and the timing of post-LGM ice-sheet retreat are poorly constrained. Several glaciological models reconstructed widespread grounding and major thickening of the Antarctic Ice Sheet in the Weddell Sea sector at the LGM. In contrast, recently published onshore data and modelling results concluded only very limited LGM-thickening of glaciers and ice streams feeding into the modern Filchner and Ronne ice shelves. These studies concluded that during the LGM ice shelves rather than grounded ice covered the Filchner and Ronne troughs, two deep palaeo-ice stream troughs eroded into the southern Weddell Sea shelf. Here we review previously published and unpublished marine geophysical and geological data from the southern Weddell Sea shelf. The stratigraphy and geometry of reflectors in acoustic sub-bottom profiles are similar to those from other West Antarctic palaeo-ice stream troughs, where grounded ice had advanced to the shelf break at the LGM. Numerous cores from the southern Weddell Sea shelf recovered sequences with properties typical for subglacially deposited tills or subglacially compacted sediments. These data sets give evidence that grounded ice had advanced across the shelf during the past, thereby grounding in even the deepest parts of the Filchner and Ronne troughs. Radiocarbon dates from glaciomarine sediments overlying the subglacial deposits are limited, but indicate that the ice grounding occurred at the LGM and that ice retreat started before ~15.1 corrected 14C kyrs before present (BP) on the outer shelf and before ~7.7 corrected 14C kyrs BP on the inner shelf, which is broadly synchronous with ice retreat in other Antarctic sectors. The apparent mismatch between the ice-sheet reconstructions from marine and terrestrial data can be attributed to ice streams with very low surface profiles (similar to those of "ice plains") that had advanced through Filchner Trough and Ronne Trough at the LGM. Considering the global sea-level lowstand of ~130 metres below present, a low surface slope of the expanded LGM-ice sheet in the southern Weddell Sea can reconcile grounding-line advance to the shelf break with limited thickening of glaciers and ice streams in the hinterland. This scenario implies that ice-sheet growth in the Weddell Sea sector during the LGM and ice-sheet drawdown throughout the last deglaciation could only have made minor contributions to the major global sea-level fluctuations during these times.