Long-term cellular and regional specificity of the photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina

This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-alpha (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachment.

LIFE CYCLE ASSESSMENTS (LCAs) OF PYROLYSIS-BASED GASOLINE AND DIESEL FROM DIFFERENT REGIONAL FEEDSTOCKS: CORN STOVER, SWITCHGRASS, SUGAR CANE BAGASSE, WASTE WOOD, GUINEA GRASS, ALGAE, AND ALBIZIA

Renewable hydrocarbon biofuels are being investigated as possible alternatives to conventional liquid transportation fossil fuels like gasoline, kerosene (aviation fuel), and diesel. A diverse range of biomass feedstocks such as corn stover, sugarcane bagasse, switchgrass, waste wood, and algae, are being evaluated as candidates for pyrolysis and catalytic upgrading to produce drop-in hydrocarbon fuels. This research has developed preliminary life cycle assessments (LCA) for each feedstock-specific pathway and compared the greenhouse gas (GHG) emissions of the hydrocarbon biofuels to current fossil fuels. As a comprehensive study, this analysis attempts to account for all of the GHG emissions associated with each feedstock pathway through the entire life cycle. Emissions from all stages including feedstock production, land use change, pyrolysis, stabilizing the pyrolysis oil for transport and storage, and upgrading the stabilized pyrolysis oil to a hydrocarbon fuel are included. In addition to GHG emissions, the energy requirements and water use have been evaluated over the entire life cycle. The goal of this research is to help understand the relative advantages and disadvantages of the feedstocks and the resultant hydrocarbon biofuels based on three environmental indicators; GHG emissions, energy demand, and water utilization. Results indicate that liquid hydrocarbon biofuels produced through this pyrolysis-based pathway can achieve greenhouse gas emission savings of greater than 50% compared to petroleum fuels, thus potentially qualifying these biofuels under the US EPA RFS2 program. GHG emissions from biofuels ranged from 10.7-74.3 g/MJ from biofuels derived from sugarcane bagasse and wild algae at the extremes of this range, respectively. The cumulative energy demand (CED) shows that energy in every biofuel process is primarily from renewable biomass and the remaining energy demand is mostly from fossil fuels. The CED for biofuel range from 1.25-3.25 MJ/MJ from biofuels derived from sugarcane bagasse to wild algae respectively, while the other feedstock-derived biofuels are around 2 MJ/MJ. Water utilization is primarily from cooling water use during the pyrolysis stage if irrigation is not used during the feedstock production stage. Water use ranges from 1.7 - 17.2 gallons of water per kg of biofuel from sugarcane bagasse to open pond algae, respectively.

Regional variation in orthopedic surgery in Switzerland

The study systematically describes the frequency and geographic variability of major surgical interventions for musculoskeletal disorders in Switzerland. Age- and sex-standardized rates for joint replacements, arthroscopies, spine surgery and hip fracture repair were calculated for hospital service regions. Various statistical analyses were used to measure the extent of variation. The authors argue that the surgery of hip fractures can be used as index surgery in the context of analyzing variations in orthopedic surgery. Temporal trends imply that patient demand and supply factors related to clinical ambiguity and non-medical incentives of providers are far more important components leading to increased use than the sole effect of an aging population.

Climate and chemistry effects of a regional scale nuclear conflict

Previous studies have highlighted the severity of detrimental effects for life on earth after an assumed regionally limited nuclear war. These effects are caused by climatic, chemical and radiative changes persisting for up to one decade. However, so far only a very limited number of climate model simulations have been performed, giving rise to the question how realistic previous computations have been. This study uses the coupled chemistry climate model (CCM) SOCOL, which belongs to a different family of CCMs than previously used, to investigate the consequences of such a hypothetical nuclear conflict. In accordance with previous studies, the present work assumes a scenario of a nuclear conflict between India and Pakistan, each applying 50 warheads with an individual blasting power of 15 kt ("Hiroshima size") against the major population centers, resulting in the emission of tiny soot particles, which are generated in the firestorms expected in the aftermath of the detonations. Substantial uncertainties related to the calculation of likely soot emissions, particularly concerning assumptions of target fuel loading and targeting of weapons, have been addressed by simulating several scenarios, with soot emissions ranging from 1 to 12 Tg. Their high absorptivity with respect to solar radiation leads to a rapid self-lofting of the soot particles into the strato- and mesosphere within a few days after emission, where they remain for several years. Consequently, the model suggests earth's surface temperatures to drop by several degrees Celsius due to the shielding of solar irradiance by the soot, indicating a major global cooling. In addition, there is a substantial reduction of precipitation lasting 5 to 10 yr after the conflict, depending on the magnitude of the initial soot release. Extreme cold spells associated with an increase in sea ice formation are found during Northern Hemisphere winter, which expose the continental land masses of North America and Eurasia to a cooling of several degrees. In the stratosphere, the strong heating leads to an acceleration of catalytic ozone loss and, consequently, to enhancements of UV radiation at the ground. In contrast to surface temperature and precipitation changes, which show a linear dependence to the soot burden, there is a saturation effect with respect to stratospheric ozone chemistry. Soot emissions of 5 Tg lead to an ozone column reduction of almost 50% in northern high latitudes, while emitting 12 Tg only increases ozone loss by a further 10%. In summary, this study, though using a different chemistry climate model, corroborates the previous investigations with respect to the atmospheric impacts. In addition to these persistent effects, the present study draws attention to episodically cold phases, which would likely add to the severity of human harm worldwide. The best insurance against such a catastrophic development would be the delegitimization of nuclear weapons.

Regional myocardial wall thinning at multidetector computed tomography correlates to arrhythmogenic substrate in postinfarction ventricular tachycardia: assessment of structural and electrical substrate

BACKGROUND A majority of patients undergoing ablation of ventricular tachycardia have implanted devices precluding substrate imaging with delayed-enhancement MRI. Contrast-enhanced multidetector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in postinfarction ventricular tachycardia. METHODS AND RESULTS We studied 13 consecutive postinfarction patients undergoing MDCT before ablation. MDCT data were integrated with high-density 3-dimensional electroanatomic maps acquired during sinus rhythm (endocardium, 509±291 points/map; epicardium, 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT <5 mm and endocardial low voltage (correlation-R=0.82; P=0.001), but no such correlation was found in the epicardium. The WT <5 mm area was smaller than the endocardial low-voltage area (54 cm(2) [Q1-Q3, 46-92] versus 71 cm(2) [Q1-Q3, 59-124]; P=0.001). Among a total of 13 060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT <5 mm (469/538 [87%]) or at its border (100% within 23 mm). Very late LAVA (>100 ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3 mm). CONCLUSIONS Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of postinfarction ventricular tachycardia. The integration of MDCT WT with 3-dimensional electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer

Background A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. Methods In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. Results The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001). Conclusions General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

Assessing the effectiveness of a long-standing rocky intertidal protected area and its contribution to the regional conservation of species, habitats and assemblages

1. The acceptance of reserves as a useful management strategy relies on evidence of their effectiveness in preserving stocks of harvested species and conserving biodiversity. A history of ad hoc decisions in terrestrial and marine protected area planning has meant that many of these areas are contributing inefficiently to conservation goals. The conservation value of existing protected areas should be assessed when planning the placement of additional areas in a reserve network. 2. This study tested (1) the effectiveness of protection for intertidal molluscs of a marine reserve (Bouddi Marine Extension, NSW, Australia) established in 1971, and (2) the contribution of the protected area to the conservation of regional species, assemblages, and habitats. 3. The shell length and population density of one harvested (Cellana tramoserica), and three non-harvested species (Bembicium nanum, Morula marginalba, Nerita atramentosa) of intertidal molluscs were examined in the protected area and two reference locations over two seasons. 4. The heavily collected limpet C. tramoserica was significantly larger in the protected area and was the only species to exhibit a significant difference. No species significantly differed in population density between the protected area and reference locations. 5. Temporally replicated surveys of macro-molluscs at 21 locations over 75km of coastline identified that the existing protected area included 50% of species, two of five assemblage types and 19 of 20 intertidal rocky shore habitats surveyed in the study region. Reservation of a further three rocky reefs would protect a large proportion of species (71%), a representative of each assemblage and all habitat types. 6. Despite originally being selected in the absence of information on regional biodiversity, the protected area is today an effective starting point for expansion to a regional network of intertidal protected areas.

Ecosystem service trade-offs and stakeholder claims - a meso-scale study from a Madagascar biodiversity hotspot

The north-eastern escarpment of Madagascar has been labelled a global biodiversity hotspot due to its extremely high rates of endemic species which are heavily threatened by accelerated deforestation rates and landscape change. The traditional practice of shifting cultivation or "tavy" used by the majority of land users in this area to produce subsistence rice is commonly blamed for these threats. A wide range of stakeholders ranging from conservation to development agencies, and from the private to the public sector has therefore been involved in trying to find solutions to protect the remaining forest fragments and to increase agricultural production. Consequently, provisioning, regulating and socio-cultural services of this forest-mosaic landscape are fundamentally altered leading to trade-offs between them and consequently new winners and losers amongst the stakeholders at different scales. However, despite a growing amount of evidence from case studies analysing local changes, the regional dynamics of the landscape and their contribution to such trade-offs remain poorely understood. This study therefore aims at using generalised landscape units as a base for the assessment of multi-level stakeholder claims on ecosystem services to inform negotiation, planning and decision making at a meso-scale. The presented study applies a mixed-method approach combining remote sensing, GIS and socio-economic methods to reveal current landscape dynamics, their change over time and the corresponding ecosystem service trade-offs induced by diverse stakeholder claims on the regional level. In a first step a new regional land cover classification for three points in time (1995, 2005 and 2011) was conducted including agricultural classes characteristic for shifting cultivation systems. Secondly, a novel GIS approach, termed “landscape mosaics approach” originally developed to assess dynamics of shifting cultivation landscapes in Laos was applied. Through this approach generalised landscape mosaics were generated allowing for a better understanding of changes in land use intensities instead of land cover. As a next step we will try to use these landscape units as proxies to map provisioning and regulating ecosystem services throughout the region. Through the overlay with other regional background data such as accessibility and population density and information from a region-wide stakeholder analysis, multiscale trade-offs between different services will be highlighted. The trade-offs observed on the regional scale will then be validated through a socio-economic ground-truthing within selected sites at the local scale. We propose that such meso-scale knowledge is required by all stakeholders involved in decision making towards sustainable development of north-eastern Madagascar.

Ultrasound-guided block of sciatic and femoral nerves: an anatomical study

The sheep is a popular animal model for human biomechanical research involving invasive surgery on the hind limb. These painful procedures can only be ethically justified with the application of adequate analgesia protocols. Regional anaesthesia as an adjunct to general anaesthesia may markedly improve well-being of these experimental animals during the postoperative period due to a higher analgesic efficacy when compared with systemic drugs, and may therefore reduce stress and consequently the severity of such studies. As a first step 14 sheep cadavers were used to establish a new technique for the peripheral blockade of the sciatic and the femoral nerves under sonographic guidance and to evaluate the success rate by determination of the colorization of both nerves after an injection of 0.5 mL of a 0.1% methylene blue solution. First, both nerves were visualized sonographically. Then, methylene blue solution was injected and subsequently the length of colorization was measured by gross anatomical dissection of the target nerves. Twenty-four sciatic nerves were identified sonographically in 12 out of 13 cadavers. In one animal, the nerve could not be ascertained unequivocally and, consequently, nerve colorization failed. Twenty femoral nerves were located by ultrasound in 10 out of 13 cadavers. In three cadavers, signs of autolysis impeded the scan. This study provides a detailed anatomical description of the localization of the sciatic and the femoral nerves and presents an effective and safe yet simple and rapid technique for performing peripheral nerve blocks with a high success rate.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).

Adapting agricultural land management to climate change: a regional multi-objective optimization approach

In several regions of the world, climate change is expected to have severe impacts on agricultural systems. Changes in land management are one way to adapt to future climatic conditions, including land-use changes and local adjustments of agricultural practices. In previous studies, options for adaptation have mostly been explored by testing alternative scenarios. Systematic explorations of land management possibilities using optimization approaches were so far mainly restricted to studies of land and resource management under constant climatic conditions. In this study, we bridge this gap and exploit the benefits of multi-objective regional optimization for identifying optimum land management adaptations to climate change. We design a multi-objective optimization routine that integrates a generic crop model and considers two climate scenarios for 2050 in a meso-scale catchment on the Swiss Central Plateau with already limited water resources. The results indicate that adaptation will be necessary in the study area to cope with a decrease in productivity by 0–10 %, an increase in soil loss by 25–35 %, and an increase in N-leaching by 30–45 %. Adaptation options identified here exhibit conflicts between productivity and environmental goals, but compromises are possible. Necessary management changes include (i) adjustments of crop shares, i.e. increasing the proportion of early harvested winter cereals at the expense of irrigated spring crops, (ii) widespread use of reduced tillage, (iii) allocation of irrigated areas to soils with low water-retention capacity at lower elevations, and (iv) conversion of some pre-alpine grasslands to croplands.

Adaptation options under climate change for multifunctional agriculture: a simulation study for western Switzerland

Besides its primary role in producing food and fiber, agriculture also has relevant effects on several other functions, such as management of renewable natural resources. Climate change (CC) may lead to new trade-offs between agricultural functions or aggravate existing ones, but suitable agricultural management may maintain or even improve the ability of agroecosystems to supply these functions. Hence, it is necessary to identify relevant drivers (e.g., cropping practices, local conditions) and their interactions, and how they affect agricultural functions in a changing climate. The goal of this study was to use a modeling framework to analyze the sensitivity of indicators of three important agricultural functions, namely crop yield (food and fiber production function), soil erosion (soil conservation function), and nutrient leaching (clean water provision function), to a wide range of agricultural practices for current and future climate conditions. In a two-step approach, cropping practices that explain high proportions of variance of the different indicators were first identified by an analysis of variance-based sensitivity analysis. Then, most suitable combinations of practices to achieve best performance with respect to each indicator were extracted, and trade-offs were analyzed. The procedure was applied to a region in western Switzerland, considering two different soil types to test the importance of local environmental constraints. Results show that the sensitivity of crop yield and soil erosion due to management is high, while nutrient leaching mostly depends on soil type. We found that the influence of most agricultural practices does not change significantly with CC; only irrigation becomes more relevant as a consequence of decreasing summer rainfall. Trade-offs were identified when focusing on best performances of each indicator separately, and these were amplified under CC. For adaptation to CC in the selected study region, conservation soil management and the use of cropped grasslands appear to be the most suitable options to avoid trade-offs.

A dosimetric study of radionuclide therapy for bone marrow ablation

In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 ($\sp{166}$Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of $\sp{166}$Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of $\sp{166}$Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of $\sp{166}$Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head.^ A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six $\sp{166}$Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with radiation dose estimates for the bone marrow calculated from the standard and regional technique. The results showed the regional technique values correlated more closely to several clinical response parameters. (Abstract shortened by UMI.) ^

Air-Sea Interactions During the Passage of a Winter Storm Over the Gulf Stream: A Three-Dimensional Coupled Atmosphere-Ocean Model Study

A three-dimensional, regional coupled atmosphere-ocean model with full physics is developed to study air-sea interactions during winter storms off the U. S. east coast. Because of the scarcity of open ocean observations, models such as this offer valuable opportunities to investigate how oceanic forcing drives atmospheric circulation and vice versa. The study presented here considers conditions of strong atmospheric forcing (high wind speeds) and strong oceanic forcing (significant sea surface temperature (SST) gradients). A simulated atmospheric cyclone evolves in a manner consistent with Eta reanalysis, and the simulated air-sea heat and momentum exchanges strongly affect the circulations in both the atmosphere and the ocean. For the simulated cyclone of 19-20 January 1998, maximum ocean-to-atmosphere heat fluxes first appear over the Gulf Stream in the South Atlantic Bight, and this results in rapid deepening of the cyclone off the Carolina coast. As the cyclone moves eastward, the heat flux maximum shifts into the region near Cape Hatteras and later northeast of Hatteras, where it enhances the wind locally. The oceanic response to the atmospheric forcing is closely related to the wind direction. Southerly and southwesterly winds tend to strengthen surface currents in the Gulf Stream, whereas northeasterly winds weaken the surface currents in the Gulf Stream and generate southwestward flows on the shelf. The oceanic feedback to the atmosphere moderates the cyclone strength. Compared with a simulation in which the oceanic model always passes the initial SST to the atmospheric model, the coupled simulation in which the oceanic model passes the evolving SST to the atmospheric model produces higher ocean-to-atmosphere heat flux near Gulf Stream meander troughs. This is due to wind-driven lateral shifts of the stream, which in turn enhance the local northeasterly winds. Away from the Gulf Stream the coupled simulation produces surface winds that are 5 similar to 10% weaker. Differences in the surface ocean currents between these two experiments are significant on the shelf and in the open ocean.

Assessment of Skill and Portability in Regional Marine Biogeochemical Models: Role of Multiple Planktonic Groups

Application of biogeochemical models to the study of marine ecosystems is pervasive, yet objective quantification of these models' performance is rare. Here, 12 lower trophic level models of varying complexity are objectively assessed in two distinct regions (equatorial Pacific and Arabian Sea). Each model was run within an identical one-dimensional physical framework. A consistent variational adjoint implementation assimilating chlorophyll-a, nitrate, export, and primary productivity was applied and the same metrics were used to assess model skill. Experiments were performed in which data were assimilated from each site individually and from both sites simultaneously. A cross-validation experiment was also conducted whereby data were assimilated from one site and the resulting optimal parameters were used to generate a simulation for the second site. When a single pelagic regime is considered, the simplest models fit the data as well as those with multiple phytoplankton functional groups. However, those with multiple phytoplankton functional groups produced lower misfits when the models are required to simulate both regimes using identical parameter values. The cross-validation experiments revealed that as long as only a few key biogeochemical parameters were optimized, the models with greater phytoplankton complexity were generally more portable. Furthermore, models with multiple zooplankton compartments did not necessarily outperform models with single zooplankton compartments, even when zooplankton biomass data are assimilated. Finally, even when different models produced similar least squares model-data misfits, they often did so via very different element flow pathways, highlighting the need for more comprehensive data sets that uniquely constrain these pathways.