AMPEROMETRIC DETECTION OF AMINO-ACIDS IN A FLOW-INJECTION SYSTEM WITH A NICKEL(II)-MODIFIED ELECTRODE WITH AN EASTMAN-AQ POLYMER FILM

Amperometic flow measurements were made at +0.55 V (vs. Ag/AgCl) in 0.1 mol l-1 KOH electrolyte with an Ni(II) chemically modified electrode (CME) with an Eastman-AQ polymer film. The use and characteristics of a Ni(II)-containing crystalline and polymer-modified electrode obtained by a double coating step as a detector for amino acids in a flow-injection system using reversed-phase liquid chromatography are described. The detection of these analytes is based on the higher oxidation state of nickel (NiOOH) controlled by the applied potential. The electroanalytical parameters and the detection current for a series of amines and amino acids were investigated. The use of such a CME in the flow-injection technique was found to be suitable in a solution at low pH. The linear range for glycine is 5 X 10(-6)-0.1 mol 1-1 with a detection limit of 1.0 X 10(-6) mol l-1. A 1 X 10(-4) mol 1-1 mixture of serine and tyrosine was also detected after separation on an Nucleosil C18 column.

ELECTROCATALYSIS AND DETERMINATION OF HYDRAZINE COMPOUNDS IN LIQUID-CHROMATOGRAPHY AT A MIXED-VALENT COBALT OXIDE CYANOCOBALTATE FILM ELECTRODE

A glassy carbon electrode coated with an electrodeposited film of mixed-valent cobalt oxide/cyanocobaltate (Co-O/CN-Co) enabled hydrazine compounds to be catalytically oxidized at the greatly reduced overpotential and in a wide operational pH range (pH 2.0-7.0). Electrocatalytic activity at the Co-O/CN-Co modified electrode was evaluated with respect to solution pH, film thickness, supporting electrolyte ions, potential scan rate, operating potential, concentration dependence and other variables. The Co-O/CN-Co film electrode was completely compatible with a conventional reversed-phase liquid chromatographic (RP-LC) system. Practical RP-LC amperometric detection (RP-LCEC) of hydrazines was performed. A dynamic linear response range over three orders of magnitude and a detection limit at the pmol level were readily obtained. The Co-O/CN-CO film electrode exhibited excellent electrocatalytic stability in the flowing streams.

ELECTROCHEMICAL STUDY OF ISOPOLY-OXOMETALLATES AND HETEROPOLY-OXOMETALLATES FILM MODIFIED MICROELECTRODES .3. FURTHER STUDY OF ELECTRODE PROCESS OF ISOPOLYMOLYBDIC ANION DOPED IN POLYANILINE FILM

The isopolymolybdic anion-polyaniline film modified carbon fiber (CF) microelectrode with high stability and electroactivity in aqueous acid solution has been successfully prepared by cycling the potential between -0.15 V and +0.85 V vs. sce at 100 mV s-1 or applying constant potential (+0.85 V) for electropolymerization in a 0.5 M H2SO4 solution containing 5.0 x 10(-2) M aniline and 5.0 x 10(-3) M H4Mo8O26. The electrochemical behaviour of the isopolymolybdic anion entrapped in the polyaniline film is strongly influenced by the sweep-potential range besides the acidity of electrolyte solution. In some acidic electrolyte solution (eg 0.5 M H2SO4), the change of the sweep-potential range causes the structure alternation of the isopolymolybdic anion and resulting in a new electrode process. The cyclic voltammogram of Mo8O264- in 0.5 M H2SO4 solution exhibits three two-electron reversible waves between +0.70 and -0.20 V. However, when the potential sweeps to the lower-limit of -0.3 V, where the fourth four-electron cathodic wave appears, the redoxidation process of the reduction product of Mo8O264- becomes relatively complicated. The 10-electron reduction product seems to change into other isopolyanion (this unknown structure isopolyanions are simply called [Mo-O]), which can be reoxidized to Mo8O264- by five successive two-electron oxidation steps from -0.30 to +0.70 V. However, when the lower-limit of the cycling potential is maintained at -0.30 V and the upper-limit reduces to +0.40 V from +0.70 V, the [Mo-O] in the film exhibits four two-electron reversible waves. We have presented a novel explanation about its electrode reaction mechanism on the basis of our experimental results.

AN INFRARED SPECTROSCOPIC STUDY OF THE STRUCTURAL PHASE-TRANSITION IN THE PEROVSKITE-TYPE LAYER COMPOUND [N-C16H33NH3]2COCL4

The solid-solid phase transitions in the perovskite-type layer compound [n- C16H33NH3]2CoCl4 have been studied by infrared spectroscopy. A new phase transition at 340 K was found by comparison with differential scanning calorimetry results. A temperature dependence study of the infrared spectra provides evidence of the occurrence of structural phase transitions related to the dynamics of the alkylammonium ions and hydrogen bonds. The main transition at 374 K corresponds to the conformational order-disorder change in the chain, which probably couples with reorientational motions of the NH3 polar heads. GTG or GTG' defects appear in the high temperature disordered phase.

ELECTRODEPOSITION OF PLATINUM PARTICLES ON GLASSY-CARBON MODIFIED WITH COBALT PORPHYRIN AND NAFION FILM AND THEIR ELECTROCATALYTIC REDUCTION OF DIOXYGEN

In this paper, five types of chemically modified electrode (CMEs) prepared with the deposition of platinum particles on various surfaces of glassy carbon (GC) modified with cobalt porphyrin and Nafion(R) solution are characterized using the electron scanning microscope (SEM). Their activities in the four-electron reduction of dioxygen to water on the basis of their electrochemical data from cyclic voltammetric and rotating ring-disk electrode (RRDE) experiments are examined and compared. Platinum particles dispersed on the GC surface adsorbed with the cobalt porphyrin exhibit the highest activity for the electrocatalytic reduction of dioxygen. However it is interesting that the cobalt ion is lost from the center of the porphyrin ring during the preparation of the cobalt porphyrin + Nafion mixture solution, while the porphyrin ring still remains in the Nafion film, as shown by EDX analysis. The incorporation of the porphyrin may change the structure of the Nafion film into a looser form, since the platinum particles dispersed in the film are more readily exposed, resulting in more favourable mass transfer and higher activity for the electrocatalytic reduction of dioxygen.

Langmuir-Blodgett film of phycobilisomes from blue-green alga Spirulina platensis

The phycobilisomes were isolated from blue-green alga Spirulina platensis, and could form monolayer film at air/water interface. The monolayer film of phycobilisomes was transferred to newly cleaved mica, and coated with gold. Scanning tunneling microscope was used to investigate the structure of the Langmuir-Blodgett film of phycobilisomes. It was shown that phycobilisomes in the monolayer arrayed in rows with core attaching on the substrate surface and rods radiating towards the air phase, this phenomenon was similar to the arrangement of phycobilisomes on cytoplasmic surface of thylakoid membrane in vivo. The possible applications of the Langmuir-Blodgett film of phycobilisomes were also discussed.

The dynamics of a topological change in a system of soap films

Hutzler, S., Saadatfar, M., van der Net, A., Weaire, D. and Cox, S.J. (2007) The dynamics of a topological change in a system of soap films. Coll. Surf. A, 323:123-131. Sponsorship: This research was supported by the European Space Agency (contracts 14914/02/NL/SH and 14308/00/NL/SH), Science Foundation Ireland. (RFP 05/REP/PHY00/6), and the EU program COST P21 (The Physics of droplets). SJC acknowledges support from EPSRC (EP/D071127/1). MS is supported by the Irish Higher Education Authority (PRTLI-IITAC).

An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.

Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

BACKGROUND: To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. METHODS: Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. RESULTS: Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). CONCLUSION: Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.

Final Report of the Phase III Archaeological Investigations at the Dr. Upton Scott House (18AP18), Annapolis, Anne Arundel County, Maryland, 1998-1999

In the summers of 1998 and 1999, the Archaeology in Annapolis project carried out archaeological investigation at the eighteenth century Dr. Upton Scott House site (18AP18)located at 4 Shipwright Street in the historic district of Annapolis, Anne Arundel County, Maryland. The Upton Scott House is significant as one of only a few Georgian houses with remnants of its original plantation-inspired landscape still visible (Graham 1998:147). Investigation was completed in agreement with the owners of the historic property, Mr. and Mrs. Paul Christian, who were interested in determining the condition and arrangement of Dr. Upton Scott’s well-documented pleasure gardens. Betty Cosans’ 1972 Archaeological Feasibility Report, the first real archaeological study of the Upton Scott House site, guided the research design and recovery efforts. Cosans determined that testing and survey in the back and side yards of the Scott property would yield important information on the use and history of the property, including that of Scott’s famous gardens. Excavation units and trenches were placed within three separate areas of backyard activity on the site which included Area One: extant brick stables in the southwest of the property; Area Two: the brick foundations of a small outbuilding located in the northwest area of the site; and Area Three: the area of Scott’s formal gardens. The research design included an interest in recovering evidence of African-American spiritual practice and domestic life at the site. Also of significant importance was an analysis of Scott’s garden beds, concerning the order and layout. Also sought was an understanding of the change in perception and use of the backyard by the various owners of the property.

Continuity and Change on an Urban Houselot: Archaeological Excavation at the 22 West Street Backlot (18AP51) of the Annapolis National Historic District, Anne Arundel County, Maryland

Intensive archaeological investigation was undertaken on an urban backlot in Annapolis, Maryland. Fieldwork was conducted on behalf of Historic Annapolis Foundation for the property's owners, King and Cornwall, Inc. Supplemental documentary research, an evaluation of existing conditions on the property, and below-ground excavation of a 35 X 70 ft. urban backlot were conducted. While the project was not a Section 106 compliance effort, the field methods and rationale for the site's investigation are comparable to those of standard Phase II site evaluations. Historical documentation attested to the fact that the 22 West Street Backlot, located along the western most edge of the Historic District of Annapolis, Maryland, had seen development and occupation since the first quarter of the eighteenth century. A substantial brick structure was known to have occupied the property in a series of altered forms for much of that period. This structure served a variety of purposes over time: a private residence in the eighteenth century, a boarding house in the nineteenth century (known as the National Hotel), a duplex in the early twentieth century, half of which remained in use until the structure was entirely razed in the 1970s after destruction by fire. Recovery and analysis of site formation processes (i.e., both cultural and natural transformations of the buried remains) indicated that sections of the site were disturbed to a depth of six feet. In contrast to what initially seemed a poor prognosis for site integrity, other areas of the backlot revealed numerous intact historical features and deposits. Structural remains from the dwelling and its associated outbuildings, additions, and attendant trash deposits were recovered. What was initiated as a program of limited testing evolved into a larger-scale undertaking that made use of largely hand-excavated units in conjunction with machine-assisted stripping of areas demonstrated to contain from four to six-foot deep sterile layers of fill. The current investigations provided a window into a portion of the city and period in its history not documented archaeologically. Moreover, this project provided valuable insight into the archaeology of the homelot within a lightly industrialized, urban context. Evidence was recovered of shifts in the layout and arrangement of the houselot as well as changing relations between individuals and the workplace--all within an urban context--an issue defined elsewhere in the archaeological literature as a significant one. No further investigations are recommended for the site, however, further analysis and interpretation of materials recovered are ongoing. In the event that the site were to undergo development, monitoring of any construction activity is recommended.

Prehistoric Pinus woodland dynamics in an upland landscape in northern Scotland: the roles of climate change and human impact

Pollen, microscopic charcoal, palaeohydrological and dendrochronological analyses are applied to a radiocarbon and tephrochronologically dated mid Holocene (ca. 8500–3000 cal B.P.) peat sequence with abundant fossil Pinus (pine) wood. The Pinus populations on peat fluctuated considerably over the period in question. Colonisation by Pinus from ca. 7900–7600 cal B.P. appears to have had no specific environmental trigger; it was probably determined by the rate of migration from particular populations. The second phase, at ca. 5000–4400 cal B.P., was facilitated by anthropogenic interference that reduced competition from other trees. The pollen record shows two Pinus declines. The first at ca. 6200–5500 cal B.P. was caused by a series of rapid and frequent climatic shifts. The second, the so-called pine decline, was very gradual (ca. 4200–3300 cal B.P.) at Loch Farlary and may not have been related to climate change as is often supposed. Low intensity but sustained grazing pressures were more important. Throughout the mid Holocene, the frequency and intensity of burning in these open Pinus–Calluna woods were probably highly sensitive to hydrological (climatic) change. Axe marks on several trees are related to the mid to late Bronze Age, i.e., long after the trees had died.

English Channel towed sledge seabed images. Phase 2: Analysis of selected tow images

During the 1970s and 1980s, the late Dr Norman Holme undertook extensive towed sledge surveys in the English Channel and some in the Irish Sea. Only a minority of the resulting images were analysed and reported before his death in 1989 but logbooks, video and film material has been archived in the National Marine Biological Library (NMBL) in Plymouth. A study was therefore commissioned by the Joint Nature Conservation Committee and as a part of the Mapping European Seabed Habitats (MESH) project to identify the value of the material archived and the procedure and cost to undertake further work (Phase 1 of the study reported here: Oakley & Hiscock, 2005). Some image analysis was undertaken as a part of Phase 1. Phase 2 (this report) was to further analyse selected images. Having determined in Phase 1 that only the 35 mm photographic transparencies provided sufficient clarity to identify species and biotopes, the tows selected for analysis were ones where 35mm images had been taken. The tows selected for analysis of images were mainly in the vicinity of Plymouth and especially along the area between Rame Head and the region of the Eddystone. The 35 mm films were viewed under a binocular microscope and the taxa that could be recognised recorded in note form. Twenty-five images were selected for inclusion in the report. Almost all of the images were of level sediment seabed. Where rocks were included, it was usually unplanned and the sled was hauled before being caught or damaged. The main biotopes or biotope complexes identified were: SS.SMU.CSaMu. Circalittoral sandy mud. Extensively present between the shore and the Eddystone Reef complex and at depths of about 48 to 52 m. At one site offshore of Plymouth Sound, the turret shell Turritella communis was abundant. In some areas, this biotope had dense anemones, Mesacmaea mitchelli and (more rarely) Cerianthus lloydii. Queen scallops, Aequipecten opercularis and king scallops, Pecten maximus, were sometimes present in small numbers. Hard substratum species such as hydroids, dead mens fingers Alcyonium digitatum and the cup coral Caryophyllia smithii occurred in a few places, probably attached to shells or stones beneath the surface. South of the spoil ground off Hilsea Point at 57m depth, the sediment was muddier but is still assigned to this biotope complex. It is notable that three small sea pens, most likely Virgularia mirabilis, were seen here. SS.SMx.CMx. Circalittoral mixed sediment. Further offshore but at about the same depth as SS.SMU.CSaMu occurred, coarse gravel with some silt was present. The sediment was characterised must conspicuously by small queen scallops, Aequipecten opercularis. Peculiarly, there were ‘bundles’ of the branching bryozoan Cellaria sp. – a species normally found attached to rock. It could not be seen whether these bundles of Cellaria had been brought-together by terebellid worms but it is notable that Cellaria is recorded in historical surveys. As with many other sediments, there were occasional brittle stars, Ophiocomina nigra and Ophiura ophiura. Where sediments were muddy, the burrowing anemone Mesacmaea mitchelli was common. Where pebbles or cobbles occurred, there were attached species such as Alcyonium digitatum, Caryophyllia smithii and the fleshy bryozoan Alcyonidium diaphanum. Undescribed biotope. Although most likely a part of SS.SMx.CMx, the biotope visually dominated by a terebellid worm believed to be Thelepus cincinnatua, is worth special attention as it may be an undescribed biotope. The biotope occurred about 22 nautical miles south of the latitude of the Eddystone and in depths in excess of 70 m. SS.SCS.CCS.Blan. Branchiostoma lanceolatum in circalittoral coarse sand with shell gravel at about 48m depth and less. This habitat was the ‘classic’ ‘Eddystone Shell Gravel’ which is sampled for Branchiostoma lanceolatum. However, no Branchiostoma lanceolatum could be seen. The gravel was almost entirely bare of epibiota. There were occasional rock outcrops or cobbles which had epibiota including encrusting calcareous algae, the sea fan Eunicella verrucosa, cup corals, Caryophyllia smithii, hydroids and a sea urchin Echinus esculentus. The variety of species visible on the surface is small and therefore identification to biotope not usually possible. Historical records from sampling surveys that used grabs and dredges at the end of the 19th century and early 20th century suggest similar species present then. Illustrations of some of the infaunal communities from work in the 1920’s is included in this report to provide a context to the epifaunal photographs.

English Channel towed sledge seabed images. Phase 1: scoping study and example analysis

During the 1970’s and 1980’s, the late Dr Norman Holme undertook extensive towed sledge surveys in the English Channel and some in the Irish Sea. Only a minority of the resulting images were analysed and reported before his death in 1989 but logbooks, video and film material has been archived in the National Marine Biological Library (NMBL) in Plymouth. A scoping study was therefore commissioned by the Joint Nature Conservation Committee and as a part of the Mapping European Seabed Habitats (MESH) project to identify the value of the material archived and the procedure and cost to undertake further work. The results of the scoping study are: 1. NMBL archives hold 106 videotapes (reel-to-reel Sony HD format) and 59 video cassettes (including 15 from the Irish Sea) in VHS format together with 90 rolls of 35 mm colour transparency film (various lengths up to about 240 frames per film). These are stored in the Archive Room, either in a storage cabinet or in original film canisters. 2. Reel-to-reel material is extensive and had already been selectively copied to VHS cassettes. The cost of transferring it to an accepted ‘long-life’ medium (Betamax) would be approximately £15,000. It was not possible to view the tapes as a suitable machine was not located. The value of the tapes is uncertain but they are likely to become beyond salvation within one to two years. 3. Video cassette material is in good condition and is expected to remain so for several more years at least. Images viewed were generally of poor quality and the speed of tow often makes pictures blurred. No immediate action is required. 4. Colour transparency films are in good condition and the images are very clear. They provide the best source of information for mapping seabed biotopes. They should be scanned to digital format but inexpensive fast copying is problematic as there are no between-frame breaks between images and machines need to centre the image based on between-frame breaks. The minimum cost to scan all of the images commercially is approximately £6,000 and could be as much as £40,000 on some quotations. There is a further cost in coding and databasing each image and, all-in-all it would seem most economic to purchase a ‘continuous film’ scanner and undertake the work in-house. 5. Positional information in ships logs has been matched to films and to video tapes. Decca Chain co-ordinates recorded in the logbooks have been converted to latitude and longitude (degrees, minutes and seconds) and a further routine developed to convert to degrees and decimal degrees required for GIS mapping. However, it is unclear whether corrections to Decca positions were applied at the time the position was noted. Tow tracks have been mapped onto an electronic copy of a Hydrographic Office chart. 6. The positions of start and end of each tow were entered to a spread sheet so that they can be displayed on GIS or on a Hydrographic Office Chart backdrop. The cost of the Hydrographic Office chart backdrop at a scale of 1:75,000 for the whole area was £458 incl. VAT. 7. Viewing all of the video cassettes to note habitats and biological communities, even by an experienced marine biologist, would take at least in the order of 200 hours and is not recommended. English Channel towed sledge seabed images. Phase 1: scoping study and example analysis. 6 8. Once colour transparencies are scanned and indexed, viewing to identify seabed habitats and biological communities would probably take about 100 hours for an experienced marine biologist and is recommended. 9. It is expected that identifying biotopes along approximately 1 km lengths of each tow would be feasible although uncertainties about Decca co-ordinate corrections and exact positions of images most likely gives a ±250 m position error. More work to locate each image accurately and solve the Decca correction question would improve accuracy of image location. 10. Using codings (produced by Holme to identify different seabed types), and some viewing of video and transparency material, 10 biotopes have been identified, although more would be added as a result of full analysis. 11. Using the data available from the Holme archive, it is possible to populate various fields within the Marine Recorder database. The overall ‘survey’ will be ‘English Channel towed video sled survey’. The ‘events’ become the 104 tows. Each tow could be described as four samples, i.e. the start and end of the tow and two areas in the middle to give examples along the length of the tow. These samples would have their own latitude/longitude co-ordinates. The four samples would link to a GIS map. 12. Stills and video clips together with text information could be incorporated into a multimedia presentation, to demonstrate the range of level seabed types found along a part of the northern English Channel. More recent images taken during SCUBA diving of reef habitats in the same area as the towed sledge surveys could be added to the Holme images.

ICES and PICES Strategies for Coordinating Research on the Impacts of Climate Change on Marine Ecosystems

The social, economic, and ecological consequences of projected climate change on fish and fisheries are issues of global concern. In 2012, the International Council for the Exploration of the Sea (ICES) and the North Pacific Marine Science Organization (PICES) established a Strategic Initiative on Climate Change Effects on Marine Ecosystems (SICCME) to synthesize and to promote innovative, credible, and objective science-based advice on the impacts of climate change on marine ecosystems in the Northern Hemisphere. SICCME takes advantage of the unique and complementary strengths of the two organizations to develop a research initiative that focuses on their shared interests. A phased implementation will ensure that SICCME will be responsive to a rapidly evolving research area while delivering ongoing syntheses of existing knowledge, thereby advancing new science and methodologies and communicating new insights at each phase.