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The Last Glacial Maximum extent of the North American Ice Sheets is well constrained empirically but has proven to be challenging to simulate with coupled Climate‐Ice Sheet models. Coupled Climate‐Ice Sheet models are often too computationally expensive to sufficiently explore uncertainty in input parameters, and it is unlikely that values calibrated to reproduce modern ice sheets will reproduce the known extent of the ice at the Last Glacial Maximum. To address this, we run an ensemble with a coupled Climate‐Ice Sheet model (FAMOUS‐ice), simulating the final stages of growth of the last North American Ice Sheets' maximum extent. Using this large ensemble approach, we explore the influence of numerous uncertain ice sheet albedo, ice sheet dynamics, atmospheric, and oceanic parameters on the ice sheet extent. We find that ice sheet albedo parameters determine the majority of uncertainty when simulating the Last Glacial Maximum North American Ice Sheets. Importantly, different albedo parameters are needed to produce a good match to the Last Glacial Maximum North American Ice Sheets than have previously been used to model the contemporary Greenland Ice Sheet due to differences in cloud cover over ablation zones. Thus, calibrating coupled climate‐ice sheet models on one ice sheet may produce strong biases when the model is applied to a new domain. Plain Language Summary: At the peak of the last ice age, an ice sheet covered much of North America. The extent of this ice sheet is well‐understood after decades of intensive data collection, but producing a computer simulation of the ice sheet which matches our observations has been a challenge. This is partly because of uncertainty about the "correct" model set‐up to create the best simulation, and partly because the computer models used in the simulations require large computing resources. In this paper, we present a series of simulations of the North American Ice Sheet at the peak of the last ice age using a fast‐running computer model in which the atmosphere and ice sheets interact. We run hundreds of simulations to tackle the uncertainty about the optimum values for unknown input parameters. We find that the model's representation of how reflective the ice sheet surface is has the most impact on the size and shape of the simulated ice sheet. Importantly, the parameter values that produce the best simulations of modern‐day Greenland produce poor simulations of the North American Ice Sheets during the last ice age, calling into question whether the parameters chosen for modern Greenland are appropriate from simulating ice sheets under different conditions. Key Points: Simulating the Last Glacial Maximum North American Ice Sheets successfully requires de‐tuning the coupled Climate‐Ice Sheet model FAMOUS‐iceAfter running a large ensemble, we identify multiple acceptable simulations of the LGM North American Ice SheetThe LGM North American cloud cover revealed overtuned albedo parameters to compensate for modern Greenland cloud biases [ABSTRACT FROM AUTHOR]

The cause of a rapid change in Atlantic Ocean circulation and northern cooling at the onset of Heinrich Stadial 1 ~18.5 ka is unclear. Previous studies have simulated the event using ice sheet and/or iceberg meltwater forcing, but these idealized freshwater fluxes have been unrealistically large. Here we use a different approach, driving a high‐resolution drainage network model with a recent time‐resolved global paleo‐ice sheet reconstruction to generate a realistic meltwater forcing. We input this flux to the Hadley Centre Coupled Model version 3 (HadCM3) climate model without adjusting the timing or amplitude and find that an acceleration in northern ice sheet melting (up to ~7.5 m/kyr global mean sea level rise equivalent) triggers a 20% reduction in the Atlantic Meridional Overturning Circulation. The simulated pattern of ocean circulation and climate change matches an array of paleoclimate and ocean circulation reconstructions for the onset of Heinrich Stadial 1, in terms of both rates and magnitude of change. This is achieved with a meltwater flux that matches constraints on sea level changes and ice sheet evolution around 19–18 ka. Since the rates of melting are similar to those projected for Greenland by 2200, constraining the melt rates and magnitude of climate change during Heinrich Stadial 1 would provide an important test of climate model sensitivity to future ice sheet melt. Plain Language Summary: Atlantic Ocean circulation plays a key role in redistributing heat around Earth's surface, and thus has an important influence on our climate. Because of this, sudden shifts in Atlantic Ocean circulation can drive rapid climate changes. One such example is at the onset of "Heinrich Stadial 1", 18.5 thousand years ago, when geological records show that Atlantic circulation weakened and the Northern Hemisphere cooled while the Southern Hemisphere warmed. At the time, huge ice sheets (several kilometers thick) covered much of North America and northern Europe. Climate model results suggest that the freshwater produced by these melting ice sheets is responsible for weakening the Atlantic Ocean circulation and triggering the abrupt climate changes captured in the geological records. This result helps to elucidate the complex interaction between ice sheets, ocean circulation, and climate, and how these interactions can lead to sudden shifts in climates of the past and, potentially, the future. Indeed, the rate of melting we adopt in the present model is comparable to the melting projected for the Greenland Ice Sheet by 2200. Key Points: The simulated pattern of ocean circulation and climate change matches records of the transition to Heinrich Stadial 1 ~18.5 kaThe rate of meltwater needed to drive this change (<7.5 mm/year global mean sea level rise equivalent) is much less than previously usedThe forcing is consistent with accelerated Eurasian ice sheet melting 19–18 ka, providing the likely cause of Heinrich Stadial 1 [ABSTRACT FROM AUTHOR]

Abstract: Records indicate that 14,500 years ago, sea level rose by 12–22 m in under 340 years. However, the source of the sea level rise remains contentious, partly due to the competing climatic impact of different hemispheric contributions. Antarctic meltwater could indirectly strengthen the Atlantic Meridional Overturning Circulation (AMOC), causing northern warming, whereas Northern Hemisphere ice sheet meltwater has the opposite effect. This story has recently become more intriguing, due to increasing evidence for sea level contributions from both hemispheres. Using a coupled climate model with freshwater forcing, we demonstrate that the climatic influence of southern‐sourced meltwater is overridden by northern sources even when the Antarctic flux is double the North American contribution. This is because the Southern Ocean is quickly resalinized by Antarctic Circumpolar water. These results imply that the pattern of surface climate changes caused by ice sheet melting cannot be used to fingerprint the hemispheric source of the meltwater. [ABSTRACT FROM AUTHOR]

The chronic use of L-Dopa for alleviating the motor symptoms of Parkinson's disease often produces adverse effects such as dyskinesia. Unregulated release of dopamine by serotonin axons following L-Dopa administration is a major presynaptic determinant of these abnormal involuntary movements. The present study was designed to characterize the reorganization of serotonin striatal afferents following dopaminergic denervation in a primate model of Parkinson's disease. Our sample comprised eight cynomolgus monkeys: four that were rendered parkinsonian following MPTP administration and four controls. The state of striatal serotonin and dopamine innervation was evaluated by means of immunohistochemistry with antibodies against serotonin transporter (SERT) and tyrosine hydroxylase. A detailed stereological investigation revealed a significant increase in the number of serotonin axon varicosities in the striatum of MPTP-intoxicated monkeys. This increase is particularly pronounced in the sensorimotor territory of the striatum, where the dopamine denervation is the most severe. Electron microscopic examinations indicate that, in contrast to the nucleus accumbens where the dopamine innervation is preserved, the SERT+ axon varicosities observed in the sensorimotor territory of the putamen establish twice as many synaptic contacts in MPTP-intoxicated monkeys than in controls. These findings demonstrate the highly plastic nature of the serotonin striatal afferent projections, a feature that becomes particularly obvious in the absence of striatal dopamine. Although the number of dorsal raphe serotonin neurons remains constant in parkinsonian monkeys, as shown in the present study, their ascending axonal projections undergo marked proliferative and synaptic adaptive changes that might play a significant role in the potential unregulated and ectopic release of dopamine by serotonin axons after L-Dopa treatment of Parkinson's disease. [ABSTRACT FROM AUTHOR]

The last deglaciation, which marked the transition between the last glacial and present interglacial periods, was punctuated by a series of rapid (centennial and decadal) climate changes. Numerical climate models are useful for investigating mechanisms that underpin the events, especially now that some of the complex models can be run for multiple millennia. We have set up a Paleoclimate Modelling Intercomparison Project (PMIP) working group to coordinate efforts to run transient simulations of the last deglaciation, and to facilitate the dissemination of expertise between modellers and those engaged with reconstructing the climate of the last 21 thousand years. Here, we present the design of a coordinated Core simulation over the period 21-9 thousand years before present (ka) with time varying orbital forcing, greenhouse gases, ice sheets, and other geographical changes. A choice of two ice sheet reconstructions is given, but no ice sheet or iceberg meltwater should be prescribed in the Core simulation. Additional focussed simulations will also be coordinated on an ad-hoc basis by the working group, for example to investigate the effect of ice sheet and iceberg meltwater, and the uncertainty in other forcings. Some of these focussed simulations will focus on shorter durations around specific events to allow the more computationally expensive models to take part. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is causally associated with cervical squamous cell carcinoma (SCC) and its precursor lesions. By analogy, HPV is believed to play a role in penile cancer through progression of HPV-associated penile squamous intraepithelial lesions (SIL). HPV DNA has been reported to be present in 100% of high-grade penile SIL, but the percentage of invasive or infiltrating penile SCC that was positive for HPV DNA has varied from study to study (positivity values ranging from 32% to 82%).Purpose: To ascertain whether HPV is associated with penile cancer, we used a polymerase chain reaction (PCR)-based assay to test specimens of penile SCC for the presence of HPV DNA.Methods: A total of 117 formalin-fixed, paraffin-embedded specimens of penile cancer from an equal number of patients who had been diagnosed either at the Memorial Sloan-Kettering Cancer Research Center in New York City between 1964 and 1992 or the Universidad Nacional de Asunción in Paraguay between 1980 and 1992 were analyzed. Specimens were examined without prior knowledge of the histology of the lesions. Methods were used that minimized sample contamination, thus avoiding false-positive results. PCR and Southern blot analyses were used to determine HPV type. The presence of HPV DNA was studied for association with the tumor properties histopathology, growth pattern, tumor grade, regional lymph node status, and anatomic location. Two-sided statistical tests were used to determine P values.Results: HPV DNA was detected in 26 (22.2%) of 117 specimens. In 23 (88.5%) of the 26 HPV-positive specimens, HPV type 16 (only) was identified. HPV DNA was frequently associated with SCC in areas showing basaloid and/or warty changes (nine [47.4%] of 19 specimens were HPV positive; P = .0125). More highly significant was the association of virus with basaloid SCC (nine [75%] of 12 specimens were HPV positive; P = .0005). However, HPV was not found to be associated with typical SCC of the penis (five [11.1%] of 45 specimens were HPV positive). Virus DNA was more often associated with high-grade tumors (P = .0278) exhibiting aggressive growth (P = .0382) localized to the glans penis (P = .0324). Stepwise logistic regression analysis revealed that only tumor histopathology was a significant predictor of an HPV association.Conclusions: The presence of HPV DNA was found to be significantly associated only with those penile SCC exhibiting basaloid changes. Furthermore, HPV DNA sequences tended to be associated with higher grade and more aggressive tumor localized to the glans penis. The low frequency of HPV in penile SCC implies that only a small proportion of these cancers arise from HPV-associated penile SIL. [ABSTRACT FROM AUTHOR]

The article discusses the combination of lymphodepletion with the infusion of donor T cells to carry a suicide gene for treatment of aggressive hematologic malignancies. A significant increase in the proportion of HLA-DR-expressing T cells is noted. An acute-like graft-versus-host disease is found in three patients after cell infusion. The use of lymphodepletion before cell infusion is considered helpful to improve the antitumor effect.

We present a simple method to generate a perturbed parameter ensemble (PPE) of a fully-coupled atmosphere-ocean general circulation model (AOGCM), HadCM3, without requiring flux-adjustment. The aim was to produce an ensemble that samples parametric uncertainty in some key variables and gives a plausible representation of the climate. Six atmospheric parameters, a sea-ice parameter and an ocean parameter were jointly perturbed within a reasonable range to generate an initial group of 200 members. To screen out implausible ensemble members, 20 yr pre-industrial control simulations were run and members whose temperature responses to the parameter perturbations were projected to be outside the range of 13.6±2 °C, i.e. near to the observed pre-industrial global mean, were discarded. Twenty-one members, including the standard unperturbed model, were accepted, covering almost the entire span of the eight parameters, challenging the argument that without flux-adjustment parameter ranges would be unduly restricted. This ensemble was used in 2 experiments; an 800 yr pre-industrial and a 150 yr quadrupled CO2 simulation. The behaviour of the PPE for the pre-industrial control compared well to ERA-40 reanalysis data and the CMIP3 ensemble for a number of surface and atmospheric column variables with the exception of a few members in the Tropics. However, we find that members of the PPE with low values of the entrainment rate coefficient show very large increases in upper tropospheric and stratospheric water vapour concentrations in response to elevated CO2 and one member showed an implausible nonlinear climate response, and as such will be excluded from future experiments with this ensemble. The outcome of this study is a PPE of a fully-coupled AOGCM which samples parametric uncertainty and a simple methodology which would be applicable to other GCMs. [ABSTRACT FROM AUTHOR]

We present a simple method to generate a perturbed parameter ensemble (PPE) of a fully-coupled atmosphere-ocean general circulation model (AOGCM), HadCM3, without requiring flux-adjustment. The aim was to produce an ensemble that samples parametric uncertainty in some key variables and displays a similar range of behavior as seen in multi-model ensembles (MMEs). Six atmospheric parameters, a sea-ice parameter and an ocean parameter were jointly perturbed within a reasonable range to generate an initial group of 200 members. To screen out implausible ensemble members, 20 yr pre-industrial control simulations were run and members whose tempera10 ture response to the parameter perturbations was projected to be outside the range of 13.6±2 °C, i.e. near to the observed pre-industrial global mean, were discarded. 21 members, including the standard unperturbed model, were accepted, covering almost the entire span of the eight parameters, challenging the argument that without fluxadjustment parameter ranges would be unduly restricted. This ensemble was used in 3 experiments; a 800 yr pre-industrial, a 150 yr quadrupled CO2, and a 150 yr 1% CO2 rise per annum simulation. The behavior of the PPE for the pre-industrial control compared well to the CMIP3 ensemble for a number of surface and atmospheric column variables with the exception of a few members in the Tropics. However, we find that members of the PPE with low values of the entrainment rate coefficient show very large increases in upper tropospheric and stratospheric water vapor concentrations in response to elevated CO2 and some show implausibly high climate sensitivities, and as such some of these members will be excluded from future experiments with this ensemble. The outcome of this study is a PPE of a fully-coupled AOGCM which samples parametric uncertainty with a range of behavior similar to the CMIP3 ensemble and a simple methodology which would be applicable to other GCMs. [ABSTRACT FROM AUTHOR]

VanDen Berg F, Gilligan CA, Gerdessen JC, Gregoire LAH &VanDen Bosch F (2010). Optimal weed management in crop rotations: incorporating economics is crucial. Weed Research 50, 413–424. Although the effects of crop rotation sequence and length on weed population dynamics have been studied, it is not clear whether or not the best strategy, from a weed population dynamics point of view, is also the economic optimal strategy. It is also not clear which biological and economic parameters are most important in determining this optimal strategy. We use a density-dependent periodic matrix model, integrated with an economic model, to study the effect of rotation length and weed control on the average annual net profit (ANP). The system of the weed Persicaria maculosa in carrots (crop A) and spring wheat (crop B) is used as an example case study. The bio-economic model shows that income is roughly constant with rotation length, apart from the shortest rotation sequence. These results are in agreement with a previous model study, which was restricted to biological dynamics. However, where the purely biological model suggests that weeding effort should be focussed on spring wheat years in the rotation, our bio-economic model shows that this is not a viable economic strategy. In fact, the mean ANP over a rotation is mainly determined by the ANP in carrot years (where the gross margin is high) and depends on the balance between the increase in seed population density in carrot years and its decrease in wheat years, in combination with weeding costs. The model can easily be extended to incorporate other damaging organisms, making the model broadly suitable for analysing a range of weed management strategies from an economic perspective. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The cycling of carbon on Earth exerts a fundamental influence upon the greenhouse gas content of the atmosphere, and hence global climate over millennia. Until recently, ice sheets were viewed as inert components of this cycle and largely disregarded in global models. Research in the past decade has transformed this view, demonstrating the existence of uniquely adapted microbial communities, high rates of biogeochemical/physical weathering in ice sheets and storage and cycling of organic carbon (>104 Pg C) and nutrients. Here we assess the active role of ice sheets in the global carbon cycle and potential ramifications of enhanced melt and ice discharge in a warming world. Ice sheets have long been overlooked as regulators of the global carbon cycle. In this Review, Wadham and colleagues show how the growth and retreat of ice sheets support the productivity of the oceans and variably store or release organic carbon–in effect, these frozen landscapes must be considered in future assessments of climate impacts on biogeochemical cycling. [ABSTRACT FROM AUTHOR]