Small Mammal Responses to Roadside Habitat Management in South Central Minnesota

Responses of small mammals to management of roadsides in south central Minnesota were examined from August-October in 1980 and 1981. The Minnesota Department of Natural Resources established and maintained vegetation along portions of these roadsides by planting Bromus inermis and Medicago sativa as nesting cover for ring-necked pheasants (Phasianus colchicus) and with infrequent mowing. Landowners or state and county transportation departments maintained other roadside areas by frequent mowing of native vegetation. Mowing of roadsides had a negative effect on abundance of Blarina brevicauda, Peromyscus leucopus, Microtus pennsylvanicus, and Mustela erminea during both summer and autumn and on abundance of Peromyscus maniculatus bairdii during late summer. In contrast, mowing had a positive influence on abundance of Mus musculus in roadsides planted with B. inermis and M sativa during summer and autumn. Roadsides planted with B. inermis and M sativa apparently increased the number of P. m. bairdii in autumn. The effects of roadside planting and mowing on the abundance of various species of small mammals were attributed to differences in height and density of vegetation and depth and coverage of litter

Incubation of sucrose craving: effects of reduced training and sucrose pre-loading

Abstract Time-dependent increases in cue-induced reward seeking after forced abstinence were described in rats with a history of cocaine or sucrose self-administration, suggesting reward craving incubates over time. In the present study, we examined the effects of reduced training experience, or sucrose pre-loading just prior to testing, on the incubation of sucrose craving. Sucrose seeking (responding in extinction and then for a sucrose-paired cue) increased over time in groups of rats that self-administered sucrose 6 h/day for 10 days and were tested at 1, 7, or 30 days of forced abstinence. We found that groups of rats that had self-administered 2 instead of 6 h/day showed a similar profile of responding. Incubation of sucrose craving was attenuated by free access to sucrose in home cages for 17 h immediately prior to testing assessed as extinction responding on days 1 and 30. However, this sucrose pre-loading had no effect on the time-dependent increase in responding for the sucrose-paired cue. In summary, reducing the training experience had no effect on the incubation of sucrose craving and free access to sucrose had only a limited effect-attenuating extinction responding. These results illustrate the strength of the incubation of craving and further suggest long-term changes in brain motivational circuitry following sucrose self-administration.

Stat5 determines the development of mammary alveolar cells

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell–cell contacts in PrlR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5- null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy

Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell–cell contacts in PrlR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5-null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy

Acute, but not longer-term, exposure to environmental enrichment attenuates Pavlovian cue-evoked conditioned approach and Fos expression in the prefrontal cortex in mice.

Funder: The University of Sussex Strategic Development FundsFunder: Sussex Neuroscience 4‐year PhD programmeExposure to environmental enrichment can modify the impact of motivationally relevant stimuli. For instance, previous studies in rats have found that even a brief, acute (~1 day), but not chronic, exposure to environmentally enriched (EE) housing attenuates instrumental lever pressing for sucrose-associated cues in a conditioned reinforcement setup. Moreover, acute EE reduces corticoaccumbens activity, as measured by decreases in expression of the neuronal activity marker "Fos." Currently, it is not known whether acute EE also reduces sucrose seeking and corticoaccumbens activity elicited by non-contingent or "forced" exposure to sucrose cues, which more closely resembles cue exposure encountered in daily life. We therefore measured the effects of acute/intermittent (1 day or 6 day of EE prior to test day) versus chronic (EE throughout conditioning lasting until test day) EE on the ability of a Pavlovian sucrose cue to elicit sucrose seeking (conditioned approach) and Fos expression in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and nucleus accumbens (NAc) in mice. One day, but not 6 day or chronic EE , reduced sucrose seeking and Fos in the deep layers of the dorsal mPFC. By contrast, 1 day, 6 day, and chronic EE all reduced Fos in the shallow layers of the OFC. None of the EE manipulations modulated NAc Fos expression. We reveal how EE reduces behavioral reactivity to sucrose cues by reducing activity in select prefrontal cortical brain areas. Our work further demonstrates the robustness of EE in its ability to modulate various forms of reward-seeking across species

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC. Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age \u3c 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required. Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study crossed the futility boundary for OS and was closed prior to meeting accrual target. Median follow-up was 9 months. One-year OS was not different between the groups: 60.1% [95% CI: 41.2–74.7%] for PCI and 50.8% [95% CI:34.0–65.3%] for PCI+cRT (p=0.21). Three and 12-month rates of progression were 53.3% and 79.6% for PCI, and 14.5% and 75% for PCI+cRT. Time to progression favored PCI+cRT, HR=0.53 (95% CI: 0.32–0.87, p=0.01). One-patient in each arm had Grade-4 therapy related toxicity and one had Grade-5 therapy related pneumonitis with PCI+cRT. Conclusions—OS exceeded predictions for both arms. Consolidative RT delayed progression but did not improve 1-year OS

Nonlinear Waves in Bose-Einstein Condensates: Physical Relevance and Mathematical Techniques

The aim of the present review is to introduce the reader to some of the physical notions and of the mathematical methods that are relevant to the study of nonlinear waves in Bose-Einstein Condensates (BECs). Upon introducing the general framework, we discuss the prototypical models that are relevant to this setting for different dimensions and different potentials confining the atoms. We analyze some of the model properties and explore their typical wave solutions (plane wave solutions, bright, dark, gap solitons, as well as vortices). We then offer a collection of mathematical methods that can be used to understand the existence, stability and dynamics of nonlinear waves in such BECs, either directly or starting from different types of limits (e.g., the linear or the nonlinear limit, or the discrete limit of the corresponding equation). Finally, we consider some special topics involving more recent developments, and experimental setups in which there is still considerable need for developing mathematical as well as computational tools.Comment: 69 pages, 10 figures, to appear in Nonlinearity, 2008. V2: new references added, fixed typo

Outcomes of Combined Cardiovascular Risk Factor Management Strategies in Type 2 Diabetes: The ACCORD Randomized Trial

OBJECTIVETo compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.RESEARCH DESIGN AND METHODSACCORD enrolled 10,251 type 2 diabetes patients aged 40–79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A1c goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0–7.9% (53–63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes.RESULTSIn the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50–0.91), BP (HR 0.74; 95% CI 0.55–1.00), or both (HR 0.71; 95% CI 0.52–0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02–1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group.CONCLUSIONSIn the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality