Accretion of "young" Phanerozoic subcontinental lithospheric mantle triggered by back-arc extension-the case of the Ivrea-Verbano Zone.

The subcontinental lithospheric mantle (SCLM) beneath Phanerozoic regions is mostly constituted by fertile lherzolites, which sharply contrast with cratonic mantle made of highly-depleted peridotites. The question of whether this chemical difference results from lower degrees of melting associated with the formation of Phanerozoic SCLM or from the refertilization of ancient depleted SCLM remains a subject of debate. Additionally, the timing and geodynamic environment of accretion of the fertile SCLM in many Phanerozoic regions are poorly constrained. We here document new geochemical and Nd-Hf isotopic data for orogenic lherzolite massifs from the Ivrea-Verbano Zone (IVZ), Southern Alps. Even though a few Proterozoic Re depletion ages are locally preserved in these mantle bodies, our data reveal that the IVZ lherzolitic massifs were "recently" accreted to the SCLM in the Upper Devonian (ca. 370 Ma) during Pangea amalgamation, with a petrochemical evolution characterized by low-degree (~ 5-12%) depletion and nearly contemporaneous pervasive to focused melt migration. The lithospheric accretion putatively took place through asthenospheric upwelling triggered by Variscan intra-continental extension in a back-arc setting related to the subduction of the Rheic Ocean. We thus conclude that the fertile sections of Phanerozoic SCLM can be accreted during "recent" events of back-arc continental extension, even where Os isotopes preserve memories of melting events in much older times.

Biological soil crusts decrease infiltration but increase erosion resistance in a human-disturbed tropical dry forest.

Under continuous human disturbance, regeneration is the basis for biodiversity persistence and ecosystem service provision. In tropical dry forests, edaphic ecosystem engineering by biological soil crusts (biocrusts) could impact regeneration by influencing erosion control and soil water and nutrient fluxes, which impact landscape hydrology, geomorphology, and ecosystem functioning. This study investigated the effect of cyanobacteria-dominated biocrusts on water infiltration and aggregate stability in a human-modified landscape of the Caatinga dry forest (NE Brazil), a system characterized by high levels of forest degradation and increasing aridity. By trapping dust and swelling of cyanobacterial filaments, biocrusts can seal soil surfaces and slow down infiltration, which potentially induces erosion. To quantify hydraulic properties and erosion control, we used minidisc-infiltrometry, raindrop-simulation, and wet sieving at two sites with contrasting disturbance levels: an active cashew plantation and an abandoned field experiencing forest regeneration, both characterized by sandy soils. Under disturbance, biocrusts had a stronger negative impact on infiltration (reduction by 42% vs. 37% during regeneration), although biocrusts under regenerating conditions had the lowest absolute sorptivity (0.042 ± 0.02 cm s-1/2) and unsaturated hydraulic conductivity (0.0015 ± 0.0008 cm s-1), with a doubled water repellency. Biocrusts provided high soil aggregate stability although stability increased considerably with progression of biocrust succession (raindrop simulation disturbed: 0.19 ± 0.22 J vs. regenerating: 0.54 ± 0.22 J). The formation of stable aggregates by early successional biocrusts on sandy soils suggests protection of dry forest soils even on the worst land use/soil degradation scenario with a high soil erosion risk. Our results confirm that biocrusts covering bare interspaces between vascular plants in human-modified landscapes play an important role in surface water availability and erosion control. Biocrusts have the potential to reduce land degradation, but their associated ecosystem services like erosion protection, can be impaired by disturbance. Considering an average biocrust coverage of 8.1% of the Caatinga landscapes, further research should aim to quantify the contribution of biocrusts to forest recovery to fully understand the role they play in the functioning of this poorly explored ecosystem.

An overview on the treatment and outcome factors of ankle fractures in elderly men and women aged 80 and over: a systematic review.

INTRODUCTION: This article is a systematic review of the literature on elderly aged 80 and over with an ankle fracture. Low energy trauma fractures are a major public health burden in developed countries that have aged populations. Ankle fractures are the third most common fractures after hip and wrist fractures. The purpose of this review is to provide an overview of the treatments and the used outcome factors. METHODS: PubMed, Embase, Cochrane Library, and CINAHL were searched to retrieve relevant studies. Studies published in English or Dutch concerning the treatment of ankle fractures in patients aged 80 and over were included. RESULTS: Initially 2054 studies were found in the databases. After removing duplicate entries, 1182 remained. Finally, after screening six studies were included, of which three cohorts studies and three case series. Six different treatments were identified and described; ORIF, transarticular Steinmann pin, plaster cast with or without weight-bearing, Gallagher nail and the TCC nail. Furthermore, 32 outcome factors were identified. DISCUSSION: The various studies show that practitioners are careful with early weight-bearing. However, if we look closely to the results and other literature, this seems not necessary and it could potentially be of great value to implement early weight-bearing in the treatment. Furthermore, quality of life seems underreported in this research field. CONCLUSIONS: ORIF with plaster cast and permissive weight-bearing should be considered for this population since it seems to be a safe possibility for a majority of the relatively healthy patients aged 80 and over. In cases where surgery is contra-indicated and a plaster cast is the choice of treatment, early weight-bearing seems to have a positive influence on the outcome in the very old patient.

Lichens Bite the Dust - A Bioweathering Scenario in the Atacama Desert.

Bioweathering mediated by microorganisms plays a significant role in biogeochemical cycles on global scales over geological timescales. Single processes induced by specific taxa have been described but could rarely be demonstrated for complex communities that dominate whole landscapes. The recently discovered grit crust of the coastal Atacama Desert, which is a transitional community between a cryptogamic ground cover and a rock-bound lithic assemblage, offers the unique chance to elucidate various bioweathering processes that occur simultaneously. Here, we present a bioweathering scenario of this biocenosis including processes such as penetration of the lithomatrix, microbial responses to wet-dry cycles, alkalinolysis, enzyme activity, and mineral re-localization. Frequently occurring fog, for example, led to a volume increase of microorganisms and the lithomatrix. This, together with pH shifts and dust accumulation, consequently results in biophysical breakdown and the formation of a terrestrial protopedon, an initial stage of pedogenesis fueled by the grit crust.

A Reevaluation of the Death of Vincent van Gogh: Suicide or Murder? The Need for a Definitive Autopsy.

Vincent van Gogh died on July 29, 1890, from an apparent gunshot wound to the belly sustained approximately 30 hours earlier on July 27. Although little is known how Vincent sustained his mortal wound, art historians have long believed that the death was the result of a suicide, a widely accepted "truth" for the mysterious death of the then unknown and now iconic artist. The basis and validity of this suicide narrative is still very hotly debated among van Gogh scholars to this day. We dug deeper into all the circumstantial evidence and testimonies to arrive at a comprehensive overview of the probability that it was likely impossible for Vincent to self-inflict his mortal wound.We used all the available circumstantial evidence related to the day Vincent van Gogh was wounded to present the information and conclusions as if we were before a judge as expert witnesses to answer the question: suicide or murder? If Vincent did not shoot himself in the belly (a red flag in and of itself), whoever inflicted that penetrating wound into his abdomen murdered him. In our study, results from firing the same model revolver that allegedly killed Vincent from various ranges (direct contact, intermediate, and distant) demonstrated within a reasonable degree of medical probability (greater than 50%) that it was not probable for Vincent van Gogh to shoot himself without a described powder burn.With little forensic evidence to rely on 130 years after the suspicious event, many have suggested a respectful exhumation and graveside autopsy utilizing 21 century techniques to bring resolve to this 19 century cold case. This crime, whether suicide or murder, has generated renewed interest and numerous questions surrounding the suspicious death of the most iconic artist of the 19th century. These missing forensic facts will remain buried with all the secrets Vincent took with him to his grave, unless a definitive autopsy is performed. What an autopsy could add to our forensic fact basis and understanding of this intriguing cold case is enormous and further delineated as the next step to answer these difficult, otherwise unanswerable questions and allow us to finally sign off on his death certificate with certainty.It is clearly impossible to definitively prove suicide or murder, but it is also impossible to disprove murder given the data and arguments offered in this analysis. A physician's opinion is based on the material available to him, and in this case, "our opinion as to the cause and manner of death is based on the limited amount of forensic information available. It is, therefore, our opinion, based on that limited information that in all medical probability, the cause of death is not a self-inflicted wound by Vincent van Gogh, and, thus, in all medical probability, a homicide."

Elemental constraints on the amount of recycled crust in the generation of mid-oceanic ridge basalts (MORBs).

Mid-oceanic ridge basalts (MORBs) are depleted in incompatible elements, but ridge segments far from mantle plumes frequently erupt chemically enriched MORBs (E-MORBs). Two major explanations of E-MORBs are that these basalts are generated by the melting of entrained recycled crust (pyroxenite) beneath ridges or by the melting of refertilized peridotites. These two hypotheses can be discriminated with compatible element abundances from Sc to Ge, here termed the ScGe elements. Here, we demonstrate that E-MORBs have systematically lower Ge/Si and Sc contents and slightly higher Fe/Mn and Nb/Ta ratios than depleted MORBs (D-MORBs) due to the mixing of low-degree pyroxenite melts. The Ge/Si ratio is a new tracer that effectively discriminates between melts derived from peridotite sources and melts derived from mixed pyroxenite-peridotite sources. These new data are used to estimate the distribution of pyroxenite in the mantle sources of global MORB segments.

Mercury bioaccumulation in tilefish from the northeastern Gulf of Mexico 2 years after the Deepwater Horizon oil spill: Insights from Hg, C, N and S stable isotopes.

Mercury (Hg) concentration in fish of the Gulf of the Mexico (GoM) is a major concern due to the importance of the GoM for U.S. fisheries. The Deepwater Horizon (DWH) oil spill in April 2010 in the northern GoM resulted in large amounts of oil and dispersant released to the water column, which potentially modified Hg bioaccumulation patterns in affected areas. We measured Hg species (methylmercury (MMHg) and inorganic Hg (IHg)) concentrations, and light (C, N and S) and Hg stable isotopes in muscle and liver tissues from tilefish (Lopholatilus chamaleonticeps) sampled in 2012 and 2013 along the shelf break of the northeastern GoM. Fish located close to the mouth of the Mississippi River (MR) and northwest of the DWH well-head (47 km) showed significantly lower Hg levels in muscle and liver than fish located further northeast of the DWH (>109 km), where 98% of tilefish had Hg levels in the muscle above US consumption advisory thresholds (50% for tilefish close to the DWH). Differences in light and Hg stable isotopes signatures were observed between these two areas, showing higher δ15N, and lower δ202Hg, Δ199Hg and δ34S in fish close to the DWH/MR. This suggests that suspended particles from the MR reduces Hg bioavailability at the base of the GoM food chains. This phenomenon can be locally enhanced by the DWH that resulted in increased particles in the water column as evidenced by the marine snow layer in the sediments. On the other hand, freshly deposited Hg associated with organic matter in more oligotrophic marine waters enhanced Hg bioaccumulation in local food webs. Comparing Hg isotopic composition in liver and muscle of fish indicates specific metabolic response in fish having accumulated high levels of MMHg.

Cyanobacterial populations in biological soil crusts of the northwest Negev Desert, Israel-effects of local conditions and disturbance.

Biological soil crusts (BSCs) fulfil numerous ecological functions in arid and semiarid areas. Cyanobacteria are important BSC organisms, which are responsible for carbon fixation, N2 fixation and binding of soil via extracellular polysaccharides. The cyanobacterial populations were characterised in different sampling plots established in three experimental stations along a rainfall gradient within NW Negev Desert, Israel. Cyanobacterial crust thickness and osmolyte accumulation therein decreased in plots with lower moisture. The cyanobacterial population structure also changed in different plots. We observed an increase of subsection III cyanobacteria such as Microcoleus spp. and Leptolyngbya spp. and a decreasing proportion of strains belonging to subsections I and IV in drier areas on the rainfall gradient. This population shift was also observed in the sampling plots, which were situated at various relief positions within the sand dune experimental sites. We also characterised the cyanobacterial populations within mechanically disturbed plots. After 4 years, they reached between 80% and 50% of the control populations in the northernmost and southern stations, respectively. Our results suggest that the cyanobacterial population is sensitive not only to macroscale factors but may also be subject to local climate variations and that 4 years was insufficient for complete recovery of the cyanobacterial population.

Three-dimensional structure and cyanobacterial activity within a desert biological soil crust.

Desert biological soil crusts (BSCs) are formed by adhesion of soil particles to polysaccharides excreted by filamentous cyanobacteria, the pioneers and main producers in this habitat. Biological soil crust destruction is a central factor leading to land degradation and desertification. We study the effect of BSC structure on cyanobacterial activity. Micro-scale structural analysis using X-ray microtomography revealed a vesiculated layer 1.5-2.5 mm beneath the surface in close proximity to the cyanobacterial location. Light profiles showed attenuation with depth of 1%-5% of surface light within 1 mm but also revealed the presence of 'light pockets', coinciding with the vesiculated layer, where the irradiance was 10-fold higher than adjacent crust parts at the same depth. Maximal photosynthetic activity, examined by O2 concentration profiles, was observed 1 mm beneath the surface and another peak in association with the 'light pockets'. Thus, photosynthetic activity may not be visible to currently used remote sensing techniques, suggesting that BSCs' contribution to terrestrial productivity is underestimated. Exposure to irradiance higher than 10% full sunlight diminished chlorophyll fluorescence, whereas O2 evolution and CO2 uptake rose, indicating that fluorescence did not reflect cyanobacterial photosynthetic activity. Our data also indicate that although resistant to high illumination, the BSC-inhabiting cyanobacteria function as 'low-light adapted' organisms.

Normal Organ Weights in Women: Part I-The Heart.

Cardiac enlargement is a well-known independent risk factor for sudden cardiac death, though the definition of what constitutes cardiac enlargement is not universally established. A previous study was undertaken to establish a normal range for male hearts to address this issue; the present study was designed to address the issue and to determine normal cardiac weights in adult human females. A prospective study was undertaken of healthy females dying from sudden, traumatic deaths aged 18 to 35 years. Cases were excluded if: there was a history of medical illness, including illicit drug use; prolonged medical treatment was performed; there was a prolonged period between the time of injury and death; body length and weight could not be accurately assessed; if there was significant cardiac injury; or if any illness or intoxication was identified after gross, microscopic, and toxicologic analysis, including evidence of systemic disease. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4 to 72.8 in.) with an average length of 160 cm (64 in.). The weight ranged from 35.9 to 152 kg (79 to 334 lbs) with an average weight of 65.3 kg (143 lbs). The majority of the decedents (86%) died from either ballistic or blunt force (including craniocerebral) injuries. Overall, the heart weights ranged from 156 to 422 g with an average of 245 g and a standard deviation of 52 g. Regression analysis was performed to assess the relationship between heart weight and body weight, body length, and body mass index, respectively, and found insufficient associations to enable predictability. The authors, therefore, propose establishing a normal range for heart weight in women of 148 to 296 g.

Head Trauma and Alcohol: A Lethal Combination.

There has been much recent attention regarding "concussions" and the role they may play in death. As most medical professionals are aware, concussions exist on a spectrum ranging from minimal or no loss of consciousness with no residual sequelae to diffuse axonal injury and sudden death. The location on the spectrum depends not only on the nature of the impact or blow but also on the state of the individual impacted. Three previous reports have illustrated 7 deaths due to blunt force head trauma with acute ethanol intoxication (postconcussive apnea). The present report describes 6 additional deaths, five of which were witnessed. The report discusses the pathophysiology of postconcussive apnea and concludes that the head trauma results in a concussion, which when combined with the ethanol, results in prolonged apnea by disruption of the cardiorespiratory centers leading to death. In addition, it is concluded that individuals dying from postconcussive apnea become immediately unresponsive after the head trauma, demonstrate no significant anatomic abnormalities at autopsy, and have blood ethanol concentrations ranging from 0.168 to 0.33 g/dL (mean, 0.258 g/dL; median, 0.24 g/dL).

Normal Organ Weights in Women: Part II-The Brain, Lungs, Liver, Spleen, and Kidneys.

Organomegaly can be a sign of disease and pathology, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human females. A prospective study was undertaken of healthy females who had sudden, traumatic deaths at age 18 to 35 years. Cases were excluded if there was a history of medical illness including illicit drug use, prolonged medical treatment was performed, there was a prolonged period between the time of injury and death, body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ that could have affected the weight. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4-72.8 inches) with an average length of 160 cm (64 inches). The weight ranged from 35.9 to 152 kg (79-334 lb) with an average weight of 65.3 kg (143 lb). The majority of the decedents (86%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean brain weight was 1233 g (range, 1000-1618 g); liver mean weight, 1288 g (range, 775-2395 g); spleen mean weight, 115 g (range, 51-275 g); right lung mean weight, 340 g (range, 142-835 g); left lung mean, 299 g (range, 108-736 g); right kidney mean weight, 108 g (range, 67-261 g); and the left kidney mean weight, 116 g (range, 55-274 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors therefore propose establishing a reference range for organ weights in women, much like those in use for other laboratory tests. Reference ranges (95% inclusion) are proposed: brain, 1033 to 1404 g; liver, 603 to 1767 g; spleen, less than 230 g; right lung, 101 to 589 g; left lung, 105 to 515 g; right kidney, 38 to 174 g; and left kidney, 35 to 192 g.

Copper(I)-photocatalyzed trifluoromethylation of alkenes.

Using the photoreducible Cu(II) precatalyst 2, trifluoromethylation reactions of alkenes are conducted effectively at low copper loading (0.1-0.5 mol%) on exposing the reaction mixture to sunlight/ambient light.

Common bile duct exploration in an elderly Asian population.

Common bile duct exploration (CBDE) is an accepted treatment for choledocholithiasis. This procedure is not well studied in the elderly population. Here we evaluate the results of CBDE in elderly patients (>70 years) and compare the open (group A) with the laparoscopic group (group B). A retrospective review was performed of elderly patients with proven common bile duct (CBD) stones who underwent CBDE from January 2005 to December 2009. There were 55 patients in group A and 33 patients in group B. Mean age was 77.6 years (70-91 years). Both groups had similar demographics, liver function tests, and stone size-12 mm (range, 5-28 mm). Patients who had empyema (n = 9), acute cholecystitis (n = 15), and those who had had emergency surgery (n = 28) were more likely to be in group A (P < 0.05). The mean length of stay for group A was 11.7 ± 7.3 days; for group B, 5.2 ± 6.3 days; the complication rate was higher in group A (group A, 38.2%; group B, 8.5%; P = 0.072). The overall complication and mortality rate was 29.5% and 3.4%, respectively. CBDE can be performed safely in the elderly with accepted morbidity and mortality. The laparoscopic approach is feasible and safe in elective setting even in the elderly.

Cyanobacterial Diversity in Biological Soil Crusts along a Precipitation Gradient, Northwest Negev Desert, Israel.

Cyanobacteria occur worldwide but play an important role in the formation and primary activity of biological soil crusts (BSCs) in arid and semi-arid ecosystems. The cyanobacterial diversity in BSCs of the northwest Negev desert of Israel was surveyed at three fixed sampling stations situated along a precipitation gradient in the years 2010 to 2012. The three stations also are characterized by marked differences in soil features such as soil carbon, nitrogen, or electrical conductivity. The cyanobacterial biodiversity was analyzed by sequencing inserts of clone libraries harboring partial 16S rRNA gene sequences obtained with cyanobacteria-specific primers. Filamentous, non-diazotrophic strains (subsection III), particularly Microcoleus-like, dominated the cyanobacterial community (30% proportion) in all years. Specific cyanobacterial groups showed increased (e.g., Chroococcidiopsis, Leptolyngbya, and Nostoc strains) or decreased (e.g., unicellular strains belonging to the subsection I and Scytonema strains) abundances with declining water availability at the most arid, southern station, whereas many cyanobacterial strains were frequently found in the soils of all three stations. The cyanobacterial diversity at the three sampling stations appears dependent on the available precipitation, whereas the differences in soil chemistry were of lower importance.

Handgun wounds: a review of range and location as pertaining to manner of death.

Citizens of the United States own more firearms than those in any other country, and the majority of the firearms owned are handguns. Given such prevalence, surprisingly few studies have been published describing the characteristics of deaths due to handguns. To address this gap, nonaccidental handgun deaths examined at the Bexar County Medical Examiner's Office between 2000 and 2010 were reviewed. A total of 1450 cases were identified, including 797 suicides and 653 homicides. Age, range of fire, location of wound, and manner of death were analyzed. The average age of suicide victims (46.7 years) was found to be greater than that of homicides (34.3 years). Suicidal wounds tended to be contact wounds to the head; abdominal, extremity, back, and multiple wound locations were more common in homicides as were distant and intermediate wounds. Handgun wounds to the forehead, side of head, submental, and intraoral locations were significantly more common in suicide, whereas those to the face, apex of the head, and back of the head were more common in homicides. Where possible, likelihood ratios were calculated to determine relative likelihood of suicide or homicide for specific wound locations and ranges. While each death should be analyzed based on its unique circumstances and not solely its statistical probability, these data may help inform the pathologist's conclusions.

Normal organ weights in men: part I-the heart.

It has been shown that cardiac enlargement, whether hypertrophic or dilated, is an independent risk factor for sudden cardiac death, although the definition of what constitutes cardiac enlargement is not universally established. This study was designed to address this issue and to determine normal cardiac weights in adult men. A prospective study was undertaken of healthy men dying from sudden traumatic deaths aged 18 to 35 years. Cases were excluded if there was a history of medical illness including illicit drug use; prolonged medical treatment was performed; there was a prolonged period between the time of injury and death; body length and weight could not be accurately assessed; there was significant cardiac injury; or any illness or intoxication was identified after gross and microscopic analysis, including evidence of systemic disease. A total of 232 cases met the criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had an average age of 23.9 years and ranged in length from 146 to 193 cm with an average length of 173 cm. Their weights ranged from 48.5 to 153 kg with an average weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. Overall, their heart weights ranged from 188 to 575 g with an average of 331 g and an SD of 56.7 g. Regression analysis was performed to assess the relationship between heart weight and body weight, body length, and body mass index and found insufficient associations to enable predictability. The authors, therefore, propose establishing a reference range for heart weight in men, much like those in use for other laboratory tests including hemoglobin, hematocrit, or glucose. A reference range (95% inclusion) of 233 to 383 g for the adult male human heart is proposed.

Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use for other laboratory tests including hemoglobin, hematocrit, or glucose. The following reference ranges (95% inclusion) are proposed: brain, 1179-1621 g; liver, 968-1860 g; spleen, 28-226 g; right lung, 155-720 g; left lung, 112-675 g; right kidney, 81-160 g; and left kidney, 83-176 g.

Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers.

Methods to improve plasmid-mediated transgene expression are needed for gene medicine and gene vaccination applications. To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. We report herein the development of potent minimal, antibiotic-free, high-manufacturing-yield mammalian expression vectors incorporating rationally designed additive combinations of expression enhancers. The SV40 72 bp enhancer incorporated upstream of the cytomegalovirus (CMV) enhancer selectively improved extrachromosomal transgene expression. The human T-lymphotropic virus type I (HTLV-I) R region, incorporated downstream of the CMV promoter, dramatically increased mRNA translation efficiency, but not overall mRNA levels, after transient transfection. A similar mRNA translation efficiency increase was observed with plasmid vectors incorporating and expressing the protein kinase R-inhibiting adenoviral viral associated (VA)1 RNA. Strikingly, HTLV-I R and VA1 did not increase transgene expression or mRNA translation efficiency from plasmid DNA after genomic integration. The vector platform, when combined with electroporation delivery, further increased transgene expression and improved HIV-1 gp120 DNA vaccine-induced neutralizing antibody titers in rabbits. These antibiotic-free vectors incorporating transient expression enhancers are safer, more potent alternatives to improve transgene expression for DNA therapy or vaccination.