Fixed low-dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of residual stenosis for acute ilio-femoral deep-vein thrombosis.

Patients with ilio-femoral deep-vein thrombosis (DVT) are at high risk of developing the post-thrombotic syndrome (PTS). In comparison to anticoagulation therapy alone, extended venography-guided catheter-directed thrombolysis without routine stenting of venous stenosis in patients with ilio-femoral DVT is associated with an increased risk of bleeding and a moderate reduction of PTS. We performed a prospective single-centre study to investigate safety, patency and incidence of PTS in patients with acute ilio-femoral DVT treated with fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT; 20 mg rt-PA during 15 hours) followed by routing stenting of venous stenosis, defined as residual luminal narrowing >50%, absent antegrade flow, or presence of collateral flow at the site of suspected stenosis. A total of 87 patients (age 46 ± 21 years, 60% women) were included. At 15 hours, thrombolysis success ≥50% was achieved in 67 (77%) patients. Venous stenting (mean 1.9 ± 1.3 stents) was performed in 70 (80%) patients, with the common iliac vein as the most frequent stenting site (83%). One major (1%; 95% CI, 0-6%) and 6 minor bleedings (7%; 95%CI, 3-14%) occurred. Primary and secondary patency rates at 1 year were 87% (95% CI, 74-94%) and 96% (95% CI, 88-99%), respectively. At three months, 88% (95% CI, 78-94%) of patients were free from PTS according to the Villalta scale, with a similar rate at one year (94%, 95% CI, 81-99%). In conclusion, a fixed-dose USAT regimen followed by routine stenting of underlying venous stenosis in patients with ilio-femoral DVT was associated with a low bleeding rate, high patency rates, and a low incidence of PTS.

Iron Fertilization of the Subantarctic Ocean During the Last Ice Age

John H. Martin, who discovered widespread iron limitation of ocean productivity, proposed that dust-borne iron fertilization of Southern Ocean phytoplankton caused the ice age reduction in atmospheric carbon dioxide (CO2). In a sediment core from the Subantarctic Atlantic, we measured foraminifera-bound nitrogen isotopes to reconstruct ice age nitrate consumption, burial fluxes of iron, and proxies for productivity. Peak glacial times and millennial cold events are characterized by increases in dust flux, productivity, and the degree of nitrate consumption; this combination is uniquely consistent with Subantarctic iron fertilization. The associated strengthening of the Southern Ocean’s biological pump can explain the lowering of CO2 at the transition from mid-climate states to full ice age conditions as well as the millennial-scale CO2 oscillations.

Atherogenic dyslipidemia and residual cardiovascular risk in statin-treated patients

BACKGROUND AND PURPOSE Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high triglycerides (triglycerides≥150 mg/dL). METHODS We studied subjects with stroke or transient ischemic attack in the Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM; n=19,100) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after randomization (n=10,498 and 2900, respectively). The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements. RESULTS A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06-1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95% confidence interval, 1.03-1.48 in PERFORM and hazard ratio, 1.24; 95% confidence interval, 0.93-1.65 in SPARCL). Time-varying analysis confirmed these findings. CONCLUSIONS The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy. Specific therapeutic interventions should now be trialed to address this residual risk.

Experimental evidence for the immediate impact of fertilization and irrigation upon the plant and invertebrate communities of mountain grasslands

The response of montane and subalpine hay meadow plant and arthropod communities to the application of liquid manure and aerial irrigation – two novel, rapidly spreading management practices – remains poorly understood, which hampers the formulation of best practice management recommendations for both hay production and biodiversity preservation. In these nutrient-poor mountain grasslands, a moderate management regime could enhance overall conditions for biodiversity. This study experimentally assessed, at the site scale, among low-input montane and subalpine meadows, the short-term effects (1 year) of a moderate intensification (slurry fertilization: 26.7–53.3 kg N·ha−1·year−1; irrigation with sprinklers: 20 mm·week−1; singly or combined together) on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass in the inner European Alps (Valais, SW Switzerland). Results show that (1) montane and subalpine hay meadow ecological communities respond very rapidly to an intensification of management practices; (2) on a short-term basis, a moderate intensification of very low-input hay meadows has positive effects on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass; (3) vegetation structure is likely to be the key factor limiting arthropod abundance and biomass. Our ongoing experiments will in the longer term identify which level of management intensity achieves an optimal balance between biodiversity and hay production.

Modified natural cycle in vitro fertilization an alternative in vitro fertilization treatment with lower costs per achieved pregnancy but longer treatment time

OBJECTIVE To analyze the cost and time requirement per achieved pregnancy in optimized modified natural cycle in vitro fertilization (mNC-IVF) based on a treatment protocol with very few consultations and to compare those with conventional gonadotropin-stimulated aVF (clVF) cycles. STUDY DESIGN Mono centric prospective trial. Eighty infertile patients each received 1 modified mNC-IVF cycle using low doses of the clomiphene citrate. Based on the number of consultations and the clinical pregnancy rate per cycle, the total costs and required time to achieve a pregnancy were analyzed and compared with cIVF. Calculations for cIVF were based on standard therapy protocols and outcomes of European registries. RESULTS Patients (21-42 years old, 35.4 +/- 4.7 years) undergoing mNC-IVF required on average 1.2 consultations before follicle aspiration. Pregnancy rate per transfer and per initiated cycle were 25% and 13.6%, respectively. Multiple pregnancies did not occur. According to the calculations, total costs per pregnancy rate were around 15% lower with mNC-IVF as compared to cIVF. In contrast, time to achieve an equal pregnancy rate was calculated to take around 30% longer with mNC-IVF as compared to cIVF. CONCLUSION mNC-IVF using very low dosages of clomiphene citrate avoids multiple pregnancies and is less expensive but more time consuming per achieved pregnancy when compared to clVF.

Minimal residual disease in cancer therapy - Small things make all the difference

Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer cells appear to be an important target in the attempt to eradicate residual cancer cells, and eventually cure patients who repeatedly respond to anticancer therapy but lack complete tumor eradication.

Kentucky Bluegrass Response to Potassium and Nitrogen Fertilization

The response of Kentucky bluegrass (Poa pratensis L.) to potassium (K) fertilization has been inconsistent. The objective of this research was to determine the effects of K fertilization across varying nitrogen (N) rates and clipping management on Kentucky bluegrass clipping yields, quality, tissue K concentrations, apparent N recovery, and N use efficiency. A 2 x 4 x 4 factorial was arranged in a splitplot design and repeated across two years. Main plots were clipping treatments (returned vs. removed) and subplots were N rates (0, 98, 196, and 294 kg ha(-1) yr(-1)) in combination with K rates (0, 81, 162, and 243 kg ha(-1) yr(-1)). There was no positive effect of K on clipping yields and quality even though soil extractable K levels tested low. Higher K rates, however, increased N recovery and use efficiency for all but the highest N rate. Tissue K response to K fertilization was nonlinear. Yield and quality responses were not correlated to tissue K concentration. Nonexchangeable K levels were high in the native soil, and may have provided an additional source of K for bluegrass. The results suggest that extractable K values alone may not adequately predict available K to Kentucky bluegrass in this sandy loam soil.

Clipping Management and Nitrogen Fertilization of Turfgrass: Growth, Nitrogen Utilization, and Quality

The effect of returning grass clippings on turfgrass growth and quality has not been thoroughly examined. The objective of this research was to determine the effects of returning grass clippings in combination with varying N rates on growth, N utilization, and quality of turfgrass managed as a residential lawn. Two field experiments using a cool-season turfgrass mixture were arranged as a 2 x 4 factorial in a randomized complete block design with three replicates. Treatments included two clipping management practices (returned or removed) and four N rates (equivalent to 0, 98, 196, and 392 kg N ha(-1)). Soils at the two sites were a Paxton fine sandy loam (coarse-loamy, mixed, active, mesic Oxyaquic Dystrudepts) and a variant of a Hinckley gravelly sandy loam (sandy-skeletal, mixed, mesic Typic Udorthents). Returning clippings was found to increase clipping dry matter yields (DMYs) from 30 to 72%, total N uptake (NUP) from 48 to 60%, N recovery by 62%, and N use efficiency (NUE) from 52 to 71%. Returning grass clippings did not decrease turfgrass quality, and improved it in some plots. We found that N fertilization rates could be reduced 50% or more without decreasing turfgrass quality when clippings were returned. Overall, returning grass clippings was found to improve growth and quality of turfgrass while reducing N fertilization needs.

Bentgrass response to K fertilization and K release rates from eight sand rootzone sources used in putting green construction.

There is a lack of plant response to fertilizer K in some sandy soils even though routine soil tests for soil available K are shown to be low. This lack of plant response to K fertilizer application may be explained by K release from nonexchangeable forms. Greenhouse and laboratory experiments were conducted to evaluate (a) response of bentgrass (Agrostis palustris [Agrostis stolonifera var. palustris]) cv. Pencross grown in rootzones with different sand sources to K fertilizer application and (b) K release from nonexchangeable forms from the different sand sources as an index to K availability. Experimental variables in the greenhouse were 2 K levels (0 and 250 mg K/kg soil) and 8 sand rootzone sources. Rootzone soils were sub-irrigated to ensure no K loss from leaching. Two laboratory methods (boiling 1 M HNO3 extraction and continuous leaching with 0.01 M HCl) and total K uptake by the bentgrass were employed to index K release from nonexchangeable forms for each rootzone source. K fertilizer application significantly increased bentgrass yield growing in one rootzone source and root weight in 3 rootzone sources. K uptake by bentgrass and the 2 laboratory methods showed important differences in K release from the sand rootzones. The K removed by the 2 laboratory methods was closely related to leaf tissue K and K uptake, with the 1 M HNO3 extraction method providing the closest fit. The release of K from primary minerals in some rootzones with high sand content is proceeding at rates to satisfy bentgrass requirements for K. The 1 M HNO3 extraction method may provide an alternative to the routine laboratory procedures presently being used to measure the extractable K in sand-based constructed putting greens by measuring K contributed by nonexchangeable forms.

Fall Fertilization Timing Effects on Nitrate Leaching and Turfgrass Color and Growth

Fall season fertilization is a widely recommended practice for turfgrass. Fertilizer applied in the fall, however, may be subject to substantial leaching losses. A field study was conducted in Connecticut to determine the timing effects of fall fertilization on nitrate N (NO3-N) leaching, turf color, shoot density, and root mass of a 90% Kentucky bluegrass (Poa pratensis L.), 10% creeping red fescue (Festuca rubra L.) lawn. Treatments consisted of the date of fall fertilization: 15 September, 15 October, 15 November, 15 December, or control which received no fall fertilizer. Percolate water was collected weekly with soil monolith lysimeters. Mean log10 NO3-N concentrations in percolate were higher for fall fertilized treatments than for the control. Mean NO3-N mass collected in percolate water was linearly related to the date of fertilizer application, with higher NO3-N loss for later application dates. Applying fall fertilizer improved turf color and density but there were no differences in color or density among applications made between 15 October and 15 December. These findings suggest that the current recommendation of applying N in mid- to late November in southern New England may not be compatible with water quality goals.

Effect of Sulfur and Boron Fertilization on Alfalfa

Historically, sulfur (S) deficiency has not been an issue for crop production in Iowa. Research results as recent as 2002 on corn and soybeans were consistent with previous results. The exception was a long-standing suggestion to apply S as commercial fertilizer or livestock manure for alfalfa production on sandy soils.