Heather and avocado honeys showed the most differential physicochemical characteristics with respect to the rest of monofloral honeys. (C) 2013 Elsevier Ltd. All rights reserved.”
“IMPORTANCE Preferred second-line medication for diabetes treatment after metformin failure remains

uncertain. OBJECTIVE To compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort constructed with national Veterans Health Administration, Medicare, and National Death Index databases. The study population comprised veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Propensity score matching on characteristics was performed, matching each participant who added insulin

to 5 who added a sulfonylurea. BTK inhibitor cell line Patients were followed through SB203580 September 2011 for primary analyses or September 2009 for cause-of-death analyses. MAIN OUTCOMES AND MEASURES Risk of a composite outcome of AMI, stroke hospitalization, or all-cause death was compared between therapies with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol level, hemoglobin A(1c) level, creatinine level, blood pressure, body mass index, and comorbidities. RESULTS Among 178 341 metformin monotherapy cancer metabolism inhibitor patients, 2948 added insulin and 39 990 added a sulfonylurea. Propensity score matching yielded 2436 metformin + insulin and 12 180 metformin + sulfonylurea patients. At intensification, patients had received metformin for a median of 14 months (IQR, 5-30), and hemoglobin A(1c) level was 8.1% (IQR, 7.2%-9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months). There were 172 vs 634 events for the primary outcome among patients who added insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR],1.30; 95%

Cl, 1.07-1.58; P = .009). Acute myocardial infarction and stroke rates were statistically similar, 41 vs 229 events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% Cl, 0.59-1.30; P =.52), whereas all-cause death rates were 137 vs 444 events, respectively (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% Cl, 1.15-1.79; P = .001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95% Cl, 0.71-1.34; P = .87). CONCLUSIONS AND RELEVANCE Among patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.

“
“Inputs to signaling pathways can have complex statistics that depend on the environment and on the behavioral response to previous stimuli. Such behavioral feedback is particularly important in navigation. Successful navigation relies on proper coupling between sensors, which gather information during motion, and actuators, which control behavior. Because reorientation conditions future inputs, behavioral

feedback can place sensors and actuators in an operational regime selleck chemical different from the resting state. How then can organisms maintain proper information transfer through the pathway while navigating diverse environments? In bacterial chemotaxis, robust performance is often attributed to the zero integral feedback control of the sensor, which guarantees that activity returns to resting state when the input remains constant. While this property provides sensitivity over https://www.selleckchem.com/products/AZD6244.html a wide range of signal intensities, it remains unclear how other parameters such as adaptation rate and adapted activity affect chemotactic performance, especially when considering that the swimming behavior

of the cell determines the input signal. We examine this issue using analytical models and simulations that incorporate recent experimental evidences about behavioral feedback and flagellar motor adaptation. By focusing on how sensory information carried by the response regulator is best utilized by the motor, we identify an operational regime that C59 wnt maximizes drift velocity along chemical

concentration gradients for a wide range of environments and sensor adaptation rates. This optimal regime is outside the dynamic range of the motor response, but maximizes the contrast between run duration up and down gradients. In steep gradients, the feedback from chemotactic drift can push the system through a bifurcation. This creates a non-chemotactic state that traps cells unless the motor is allowed to adapt. Although motor adaptation helps, we find that as the strength of the feedback increases individual phenotypes cannot maintain the optimal operational regime in all environments, suggesting that diversity could be beneficial.”
“Levy flight foraging represents an innovative paradigm for the analysis of animal random search by including models of heavy-tailed distribution of move length, which complements the correlated random walk paradigm that is founded on Brownian walks. Theory shows that the efficiency of the different foraging tactics is a function of prey abundance and dynamics with Levy flight being especially efficient in poor prey fields. Levy flights have been controversial in some quarters, because they previously have been wrongly ascribed to many species through the employment of inappropriate statistical techniques and by misunderstanding movement pattern data.

We hypothesized that colloid solutions, compared with crystalloid, would produce the largest increase in CO and have the lowest incidence of hypotension.\n\nMETHODS: Sixty healthy term women scheduled for planned cesarean delivery under spinal anesthesia were recruited for this randomized, double-blind study. Baseline heart rate, systolic blood pressure (SBP), CO, and FTc were recorded in the left lateral tilt position. Patients were randomized to receive 1 of 3 fluid preload regimens given over 15 min: 1.5 L crystalloid (Hartman’s solution), 0.5 L of 6% w/v hydroxyethyl starch (HES) solution (HES 0.5), or I L of 6% w/v HES solution (HES 1.0). Further measurements were made after fluid loading

every 5 min for 30 min. After 30 min, spinal anesthesia was induced with hyperbaric bupivacaine 12.5 mg with fentanyl 15 mu g and recordings were continued check details every 5 min for 20 min or until surgery

GW4869 supplier started. The primary outcome, CO, was compared among groups. The incidence of hypotension (defined as a 20% reduction in SBP from the baseline), ephedrine use, and umbilical cord blood gases were also compared.\n\nRESULTS: Patient characteristics, heart rate, SBP, and cord gases were similar among groups. Although CO and FTc increased after preload in all groups (P < 0.005), this was only maintained with HES 1.0 after spinal anesthesia (P < 0.005). There were no differences among groups in the incidence of hypotension (70% vs 35%

vs 65% for Hartman’s solution, HES 0.5, and HES 1.0, respectively; P = 0.069) or mean ephedrine dose (10.4 vs 5.7 vs 9.7 mg; P = 0.26).\n\nCONCLUSION: Despite CO and FTc increases after fluid preload, particularly with HES 1.0 L, hypotension still occurred. The data suggest that CO increases after these preload regimens cannot compensate for reductions in arterial blood pressure after spinal anesthesia. (Anesth Analg 2009:109:1916-21)”
“Hypoxia/reoxygenation (H/R)-induced injury is the key factor associated with islet graft dysfunction. This study aims to examine the effect of mesenchymal stem cells (MSCs) on islet survival and insulin secretion under H/R conditions. Islets from rats were isolated, purified, cultured with or without MSCs, and exposed to hypoxia (O(2) <= 1%) for 8 h and reoxygenation see more for 24 and 48 h, respectively. Islet function was evaluated by measuring basal and glucose-stimulated insulin secretion (GSIS). Apoptotic islet cells were quantified using Annexin V-FITC. Antiapoptotic effects were confirmed by mRNA expression analysis of hypoxia-resistant molecules, HIF-1 alpha, HO-1, and COX-2, using semi-quantitative retrieval polymerase chain reaction (RT-PCR). Insulin expression in the implanted islets was detected by immunohistological analysis. The main results show that the stimulation index (SI) of GSIS was maintained at higher levels in islets co-cultured with MSCs.

For human population-genetic data, we find that a close linear relationship previously seen between gene diversity and distance from East Africa is preserved when adjusting for the inclusion of close relatives.”
“Psittacine beak and feather disease, caused by beak and feather disease virus (BFDV), is a threat to endangered psittacine species. There is currently no vaccine against BFDV, which necessitates the development of safe and affordable vaccine candidates. A subunit vaccine based on BFDV capsid protein (CP), the major antigenic determinant, expressed in the inexpensive Hippo pathway inhibitor and highly scalable

plant expression system could satisfy these requirements. Full-length CP and a truncated CP (Delta N40 CP) were transiently expressed in tobacco (Nicotiana benthamiana) as fusions to elastin-like polypeptide (ELP). These two proteins were fused to ELPs of different lengths in order to increase expression levels and to provide a simple means of purification. The ELP fusion proteins were purified

by inverse transition cycling (ITC) and it was found that a membrane filtration-based ITC method improved the recovery of Delta N40 CP-ELP51 fusion protein relative to a centrifugation-based method. (C) 2013 Elsevier B.V. All rights reserved.”
“Molecules of the title compound, C16H19NO2S, are bent at the S atom with a C-SO2-NH-C torsion angle of -60.0 (2)degrees. The dihedral angle between the phenylsulfonyl and aniline rings is 41.7 (1)degrees. In the crystal, molecules INCB024360 are packed into centrosymmetric GW4869 price dimers through pairs of N-H center dot center dot center dot O(S) hydrogen bonds.”
“Background & aims: Adjuvant chemotherapy has frequently been associated with weight gain after breast cancer diagnosis. We aimed to prospectively evaluate body weight variations in French patients with early breast cancer.\n\nMethods: This prospective observational study included 272 breast cancer patients who were candidates for adjuvant chemotherapy. Weight and body mass index were measured at baseline visit, then at

9 and 15 months from baseline (6 and 12-month post-chemotherapy). At baseline visit, information on the benefits of weight gain prevention and healthy diet was given by a dietician. Univariate logistic regression was performed to test the association between weight gain and potential predictive factors.\n\nResults: Thirty percent of patients gained weight during the year before diagnosis, 26% were overweight and 15% were obese. At one year, the mean weight change was +1.5 kg (SD = 4.1) and +2.3% (SD = 6.0): 60% of the cohort had gained weight, with a median increase of 3.9 kg (SD = 3.0) and 5.9% (SD = 4.4). Reported weight gain during the year before diagnosis appears to be the only factor associated with the absence of post-chemotherapy weight gain (OR = 0.54, 95% Cl [0.31-0.95], p = 0.034).

Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly

increased risks of autistic disorder Belnacasan price following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100 000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100 000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100 000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using PFTα order surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100 000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100 000 person-years).\n\nCONCLUSIONS AND RELEVANCE Compared with spontaneous conception, IVF treatment overall was not

associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, Vorinostat in vitro and the increase in absolute risk associated with IVF was small. JAMA. 2013;310(1):75-84.”
“Previous efforts to develop drugs that directly inhibit the activity of mutant KRAS, the most commonly mutated human

oncogene, have not been successful. Cancer cells driven by mutant KRAS require expression of the serine/threonine kinase STK33 for their viability and proliferation, identifying STK33 as a context-dependent therapeutic target. However, specific strategies for interfering with the critical functions of STK33 are not yet available. Here, using a mass spectrometry-based screen for STK33 protein interaction partners, we report that the HSP90/CDC37 chaperone complex binds to and stabilizes STK33 in human cancer cells. Pharmacologic inhibition of HSP90, using structurally divergent small molecules currently in clinical development, induced proteasome-mediated degradation of STK33 in human cancer cells of various tissue origin in vitro and in vivo, and triggered apoptosis preferentially in KRAS mutant cells in an STK33-dependent manner. Furthermore, HSP90 inhibitor treatment impaired sphere formation and viability of primary human colon tumor-initiating cells harboring mutant KRAS.

The ability of noninvasive stress tests to predict coronary vasomotor

dysfunction in patients with nonobstructive coronary artery disease is unknown.\n\nMethods and Results – All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n = 376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of <= 50% to intracoronary acetylcholine (endothelium-dependent dysfunction) and/or a coronary flow reserve ratio of <= 2.5 to intracoronary 4EGI-1 manufacturer adenosine (endothelium-independent dysfunction). We determined the sensitivity and specificity of various noninvasive stress tests to predict coronary vasomotor dysfunction in these patients. On invasive testing, CDK inhibitor 233 patients (63%) had coronary vasomotor dysfunction, of which 187 patients (51%) had endothelium-dependent dysfunction, 109 patients (29%) had endothelium-independent dysfunction, and 63 patients (17%) had both. On noninvasive stress testing, 157 (42%) had a positive imaging study and 56 (15%) a positive ECG stress test. The noninvasive stress tests had limited diagnostic

accuracy for predicting coronary vasomotor dysfunction (41% sensitivity [95% CI, 34 to 47] and 57% specificity [95% CI, 49 to 66]), endothelium-dependent dysfunction (41% sensitivity [95% CI, 34 to 49] and 58% specificity Dihydrotestosterone [95% CI, 50 to 65]), or endothelium-independent dysfunction (46% sensitivity [95% CI, 37 to 56] and 61% specificity [95% CI, 54 to 67]). The exercise ECG test was more specific but less sensitive than the imaging tests.\n\nConclusion – This study suggests that a negative noninvasive stress test does not rule out

coronary vasomotor dysfunction in symptomatic patients with nonobstructive coronary artery disease. This underscores the need for invasive assessment or novel more sensitive noninvasive imaging for these patients. (Circ Cardiovasc Intervent. 2009;2:237-244.)”
“A melt-mixing process based on convergent-divergent flow has been used to prepare PP/MWCNT composites with a self-built convergent-divergent die (C-D die) composed of different numbers of convergent plates. Dynamic extensional deformation was generated in the C-D die, which improved the mixing effect and mixing efficiency of the composites during extrusion. The C-D die acted as a mixer for composites when mounted onto a capillary rheometer. The residence time of PP/MWCNTs melt in the extensional flow field is adjusted by changing the numbers of convergent plates and the velocity of the ram. The intensity of extensional flow field is controlled by the structure of the convergent plate and the ram velocity.

\n\nStudy Design\n\nAnalysis of a national database for all US civil trials.\n\nMethods\n\nThe Westlaw database was reviewed from 2001 to 2011. Data were compiled on the demographics of the plaintiffs, use of expert witnesses, procedures, nature of the injury, legal allegations, verdicts, and indemnities.\n\nResults\n\nOne hundred ninety-eight cases met inclusion criteria. Verdicts for the defendant/otolaryngologist

predominated (58%), whereas the average Selleckchem SCH727965 award when the verdict favored the plaintiff was $1,782,514. When otolaryngologists were used as expert witnesses by the defense, the verdict outcome statistically favored the defendant. Two of the most commonly cited legal allegations were improper performance and failure to diagnose and treat. Fifty-one cases involved allegations of wrongful death, with the overall outcome favoring the plaintiffs (51%). The average indemnities in these cases were significantly Dihydrotestosterone chemical structure higher for plaintiff verdicts at $2,552,580 versus settlements at $992,896. Forty-two cases involved malignancy, with the two most common allegations being failure to diagnose and treat (79%) and delay in diagnosis (74%).\n\nConclusions\n\nOur study reveals that in the past decade, in significant

malpractice litigations, overall outcomes favored otolaryngologists. The average awards was significantly higher when cases involved malignancy. Our analysis reveals the importance of meticulous surgical techniques and thorough preoperative evaluations. Last, when otolaryngologists are defendants in litigation, our review reiterates the value of the otolaryngologist as the defense’s expert witnesses. Laryngoscope, 124:896-901, 2014″
“Although, historically, the political power structure of Iranian society has partly been under the influence of the structures of rural, tribal, and also traditional urban culture, this trend has been accelerated after the revolution in 1979 due to extreme migrations of villagers to cities and the intermingling of the rural-urban culture and also taking power of resented social groups with rural origins. Coming to the power of these

social groups has made a kind of duality in Iran’s political power structure. This duality ASP2215 led to some turmoil and disorder among government and the people on national interests and solving the problems of the society. The present article tries to examine causes and factors affecting this dispute and considers the cognitive aspects of this issue, particularly the sociological aspects. The results of this study show that the political structure in Iran and its structural characteristics are under the influence of rural culture and socio-economic aspects. In other words, the political power structure is the result of social and rural connections. [Mohsen Alini, Maryam Bijan. A Review on Causes and Factors Affecting on the Power Structure of Rural Culture in Iranian Society of Post-Islamic Revolution. Life Sci J 2012; 9(4): 4251-4259].

Advances in our understanding of cellular and molecular actions of steroid hormones have gone beyond the important cell nuclear actions of steroid hormone selleckchem receptors to include signaling pathways that intersect with other

mediators such as neurotransmitters and neuromodulators. This has, in turn, broadened the search for and identification of steroid receptors to include nonnuclear sites in synapses, dendrites, mitochondria, and glial cells, as well as cell nuclei. The study of estrogen receptors and estrogen actions on processes related to cognition, mood, autonomic regulation, pain, and neuroprotection, among other functions, has led the way in this new view of hormone actions on the brain. In this review, we summarize past and current work in our laboratory on this topic. This exciting and growing field involving many laboratories continues to reshape our ideas and approaches to neuroendocrinology both at the bench and the bedside.”
“Synthesis of tetrasaccharide portion of ganglioside HPG-1 Selleck NCT-501 is described. The tetrasaccharide sequence, Fuc-alpha(1,8)-Neu5Gc-alpha(2,4)-Neu5Ac-alpha(2,6)-Glc, was successfully assembled by a linear strategy, in which the 1,5-lactamized sialyl galactose

acceptor and the 8-O-Lev-N-Troc-sialic acid donor were exploited as key units.”
“In an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial Ulixertinib maternal fetal concentration differences of glucose and mannose were greater in the PI-IUGR fetus; glucose: C (n = 7), 2.68 +/- 0.14 mmol/L versus PI-IUGR (n = 9), 3.18 +/- 0.16 mmol/L (P < 0.02) and mannose: C, 42.9 +/- 8.1 mu mol/L versus PI-IUGR, 68.5 +/- 19.1 mu mol/L (P < 0.001). For PI-IUGR fetuses, fetal arterial plasma myo-inositol concentrations were significantly increased (P < 0.001). The concentrations of sorbitol, glucose and fructose were significantly reduced (P < 0.03, 0.01, 0.02, respectively). The cotyledons of IUGR placentas had a significantly increased concentration

of myoinositol (P < 0.003) and decreased concentrations of sorbitol, fructose and glycerol (P < 0.01, 0.02, 0.01, respectively). Fetal hepatic concentrations of sorbitol (P < 0.001) and fructose (P < 0.03) were also significantly reduced. These profound changes in both placental and fetal concentrations of polyols and sugars in sheep PI-IUGR pregnancies support the conclusion that within the PI-IUGR placenta there is an increased flux through the glucose 6-P:inositol 1-P cyclase system and decreased flux through the polyol dehydrogenase system, leading to increased placental myo-inositol production and decreased sorbitol production. The decreased placental supply of sorbitol to the fetal liver may lead to decreased fetal hepatic fructose production.

The three basins had different recent migration patterns: Beaver Creek did not have any recent migration between sites, Libby Creek had two-way migration between sites and Gold Creek had downstream migration between sites. Sites with migration were significantly different from sites without migration in distance, number of obstructions, obstruction height to depth ratio and maximum stream gradient. When comparing the sites without

migration in Beaver Creek to the sites with Small molecule library ic50 migration in Libby and Gold creeks, the number of obstructions was the only significant variable. Multinomial logistic regression identified obstruction height to depth ratio and maximum stream gradient as the best fitting model to predict the level of migration among sites. Small irrigation diversion dams were limiting population interactions in Beaver Creek and collectively blocking steelhead migration into the stream. Variables related to stream resistance (gradient, obstruction number and obstruction height to depth ratio) were better predictors of recent migration rates than distance, and can provide important insight into migration and population demographic processes in lotic species.”
“We report a 3-year old boy with acute onset of left sided facial palsy secondary to tick infestation in the left ear. On 7th day of

follow-up, following tick removal, the facial palsy had resolved.”
“Nivalenol (NIV)

PF-04929113 nmr and deoxynivalenol (DON) are predominant Fusarium-producing mycotoxins found in grains, which are mainly produced by Fusarium asiaticum and F. graminearum. NIV is found in most of cereals grown in Korea, but the genetic basis for NIV production by F. asiaticum has not been extensively explored. In this study, 12 genes belonging to the trichothecene biosynthetic gene cluster were compared at the transcriptional level click here between two NIV-producing F. asiaticum and four DON-producing F. graminearum strains. Chemical analysis revealed that time-course toxin production patterns over 14 days did not differ between NIV and DON strains, excluding F. asiaticum R308, which was a low NIV producer. Both quantitative real-time polymerase chain reaction and Northern analysis revealed that the majority of TRI gene transcripts peaked at day 2 in both NW and DON producers, which is 2 days earlier than trichothecene accumulation in liquid medium. Comparison of the gene expression profiles identified an NW-specific pattern in two transcription factor-encoding TRI genes (TRI6 and TRI10) and TRI101, which showed two gene expression peaks during both the early and late incubation periods. In addition, the amount of trichothecenes produced by both DON and NIV producers were correlated with the expression levels of TRI genes, regardless of the trichothecene chemotypes.

\n\nResults: EphA2-Fc resulted in a greater response of endothelial cells (EC) to IR than either treatment alone. EphA2-Fc significantly increased apoptosis and decreased

clonogenic survival, tube formation and migration in irradiated EC after stimulation with vascular endothelial growth factor (VEGF), without an affecting their proliferation. No difference in proliferation or survival was found in A549 and MCF-7 tumor cells. In a co-culture model, EphA2-Fc inhibited an irradiated A549 cell-induced increase in EC migration. VEGF supplementation, as well as condiotioned medium from irradiated A549 cells, phosphorylated EphA2 in EC. The latter was abrogated by EphA2-Fc.\n\nConclusions: EC were most sensitive to a combination of Selleckchem Elafibranor EphA2 inhibition and radiotherapy. The induction of paracrine growth factors and activation of EphA2 in EC suggest a protective mechanism that tumors probably use to attenuate IR-induced antivascular effects. Our data justify further investigation to explore targeting EphA2 in tumor radiosensitivity in vivo.”
“Blunt traumatic laryngeal injury in children often leads to intralaryngeal soft-tissue damage, which can quickly compromise an already small airway. Injuries requiring operative intervention have historically been repaired Napabucasin cost via open approaches such as thyrotomy and laryngofissure. These approaches carry significant long-term sequelae that can compromise the airway, deglutition,

and voice. We describe a safe and effective alternative to open repair that includes Selleck EPZ 6438 the use of a botulinum toxin chemical myotomy to ensure optimal healing. We used this procedure to treat a 13-year-old boy who had experienced a traumatic avulsion of the true vocal folds. Postoperatively, his voice outcome was satisfactory, as evidenced by a marked improvement

in his pediatric Voice Handicap Index score. No complication or compromise of the airway or swallowing occurred, and resolution of the botulinum effect was observed by 6 months postoperatively. The endoscopic approach supplemented by botulinum toxin injection avoids scarring and allows for safe postoperative extubation. Compared with open repair, it is associated with a shorter hospital stay and a lower risk of stenosis and fibrosis.”
“We developed independent predictive disturbance models for a full regional data set and four individual ecoregions (Full Region vs. Individual Ecoregion models) to evaluate effects of spatial scale on the assessment of human landscape modification, on predicted response of stream biota, and the effect of other possible confounding factors, such as watershed size and elevation, on model performance. We selected macroinvertebrate sampling sites for model development (n = 591) and validation (n = 467) that met strict screening criteria from four proximal ecoregions in the northeastern U.S.: North Central Appalachians, Ridge and Valley, Northeastern Highlands, and Northern Piedmont.