ECONOMICS OF SOME SWINE PRODUCTION SYSTEMS WITH REFERENCE TO ANIMAL WELFARE

Livestock Production/Industries,

Arm Flexion, Arm Extension, and Motivational Responses to Feared Stimuli

People are highly motivated to approach attractive stimuli and to avoid noxious stimuli (e.g., Lang, Bradley, & Cuthbert, 1990; Schneirla, 1959. Approach of attractive stimuli (e.g., obtaining food, pursuit of sexual relations) and avoidance of noxious stimuli (e.g., defense against predatory threat) ensure continued survival, a basic goal of all living organisms. And yet, sometimes approach/avoidance behavior is maladaptive. For instance, individuals with intense fears of spiders experience strong avoidance motivation in spite of the relative harmlessness of most spiders. The research reported here evaluated whether a simple, easily executed bodily manipulation can dampen the strong avoidance motivation that typically results when a person is exposed to cues of a feared stimulus (e.g., Hamm, Cuthbert, Globisch, & Vaitl, 1997). Previous research in our laboratory (Thibodeau, 2011) and others (e.g., Cacioppo, Priester, & Berntson, 1993) suggests that the execution of simple actions normally associated with approach behavior (e.g., arm flexion, as when pulling attractive objects near) is sufficient, by itself, to elicit approach motivation. The current research explored whether spider- and snake-fearful undergraduates and non-fearful controls who were exposed to photographs of fear-relevant stimuli could diminish the size and strength of avoidance motives simply by concurrently engaging in an approach-related action. The startle probe (Lang et al., 1990) was used to index the strength of participants’ avoidance motives. METHOD Forty undergraduates participated in the study for course credit. Fearful participants (n = 24) obtained scores above 20 on self-report questionnaires measuring snake or spider fear (Klorman, Weerts, Hastings, Melamed, & Lang, 1974); controls (n = 16) obtained scores below 6. The startle reflex was indexed by electromyographic (EMG) recording of the orbicularis oculi (“blink”) muscle, contraction of which causes the sudden closure of the eyelids that represents a key element of the startle response. Participants viewed a series of 45 pictures (15 spiders or snakes, 15 household objects, 15 fixation crosses) and concurrently performed arm flexion (an approach action), arm extension (an avoidance action), or squeezed the edge of a table (a neutral control action); all pictures and actions were presented in a quasi-randomized sequence. Bursts of 50-ms white noise (98 dB) were unpredictably presented to elicit the startle reflex. We followed standard procedures for the reduction and scoring of startle data (Blumenthal et al., 2005). RESULTS AND DISCUSSION Contrary to predictions, the motivational actions were not related to the size of the startle reflex (Action main effect; p = .27). This pattern held for both groups (Action x Group interaction; p = .17), and it was not moderated by Picture Type (Action x Picture Type interaction; p = .90). The three-way interaction was also nonsignificant (p = .15). Importantly, however, a significant main effect of Picture Type (F[2,76] = 7.03, p = .002) confirmed a previously documented pattern of heightened startle reactivity during viewing of fear-relevant pictures (e.g., Hamm et al., 1997). Overall, the present data suggest that the motivational actions utilized here (Cacioppo et al., 1993; Thibodeau, 2011) are insufficient to moderate avoidance-related emotional responses to feared stimuli

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer

The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non–small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy

Trading Justice for Peace? Reframing reconciliation in TRC processes in South Africa, Canada and Nordic countries

Conflict in its various manifestations continues to be a defining feature in many places throughout the world. In an attempt to address such conflict, various forms of a Truth and Reconciliation Commission (TRC) have been introduced to facilitate the transition from social conflict to a new dispensation. The introduction and subsequent proceedings of TRCs in South Africa, Canada and Norway are widely regarded as good examples of this approach. Against this background, a number of researchers from VID Specialized University and the University of the Western Cape had an exploratory meeting in Oslo in 2018 where the possibility for a joint research project under the broad theme of ‘discourses on reconciliation’ was first discussed. This led to two further research symposia in Cape Town and Tromsø in 2019. With the inclusion of specialists working on the Canadian Truth and Reconciliation process, these meetings demonstrated common ground and a shared understanding of the issues at stake. Moreover, it pointed to the differences between the South African, Canadian and Norwegian Commissions. In comparing the South African, Canadian and Norwegian experiences, researchers identified that these countries were, in fact, at different stages of their respective truth and reconciliation processes. This has prompted scholars to revisit and problematise these processes in relation to ongoing societal challenges. In all cases, it is quite apparent that reconciliation between individuals and groups remains a significant challenge

Trading Justice for Peace? Reframing reconciliation in TRC processes in South Africa, Canada and Nordic countries

Conflict in its various manifestations continues to be a defining feature in many places throughout the world. In an attempt to address such conflict, various forms of a Truth and Reconciliation Commission (TRC) have been introduced to facilitate the transition from social conflict to a new dispensation. The introduction and subsequent proceedings of TRCs in South Africa, Canada and Norway are widely regarded as good examples of this approach. Against this background, a number of researchers from VID Specialized University and the University of the Western Cape had an exploratory meeting in Oslo in 2018 where the possibility for a joint research project under the broad theme of ‘discourses on reconciliation’ was first discussed. This led to two further research symposia in Cape Town and Tromsø in 2019. With the inclusion of specialists working on the Canadian Truth and Reconciliation process, these meetings demonstrated common ground and a shared understanding of the issues at stake. Moreover, it pointed to the differences between the South African, Canadian and Norwegian Commissions. In comparing the South African, Canadian and Norwegian experiences, researchers identified that these countries were, in fact, at different stages of their respective truth and reconciliation processes. This has prompted scholars to revisit and problematise these processes in relation to ongoing societal challenges. In all cases, it is quite apparent that reconciliation between individuals and groups remains a significant challenge

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

Purpose The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. Methods 3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. Results Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. Conclusions 3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. KEY WORDS transdermal drug delivery. microneedles. intradermal. hollow microstructures. MT

Evidence for Habitual and Goal-Directed Behavior Following Devaluation of Cocaine: A Multifaceted Interpretation of Relapse

BACKGROUND:Cocaine addiction is characterized as a chronically relapsing disorder. It is believed that cues present during self-administration become learned and increase the probability that relapse will occur when they are confronted during abstinence. However, the way in which relapse-inducing cues are interpreted by the user has remained elusive. Recent theories of addiction posit that relapse-inducing cues cause relapse habitually or automatically, bypassing processing information related to the consequences of relapse. Alternatively, other theories hypothesize that relapse-inducing cues produce an expectation of the drug's consequences, designated as goal-directed relapse. Discrete discriminative stimuli signaling the availability of cocaine produce robust cue-induced responding after thirty days of abstinence. However, it is not known whether cue-induced responding is a goal-directed action or habit. METHODOLOGY/PRINCIPAL FINDINGS:We tested whether cue-induced responding is a goal-directed action or habit by explicitly pairing or unpairing cocaine with LiCl-induced sickness (n = 7/group), thereby decreasing or not altering the value of cocaine, respectively. Following thirty days of abstinence, no difference in responding between groups was found when animals were reintroduced to the self-administration environment alone, indicating habitual behavior. However, upon discriminative stimulus presentations, cocaine-sickness paired animals exhibited decreased cue-induced responding relative to unpaired controls, indicating goal-directed behavior. In spite of the difference between groups revealed during abstinent testing, no differences were found between groups when animals were under the influence of cocaine. CONCLUSIONS/SIGNIFICANCE:Unexpectedly, both habitual and goal-directed responding occurred during abstinent testing. Furthermore, habitual or goal-directed responding may have been induced by cues that differed in their correlation with the cocaine infusion. Non-discriminative stimulus cues were weak correlates of the infusion, which failed to evoke a representation of the value of cocaine and led to habitual behavior. However, the discriminative stimulus-nearly perfectly correlated with the infusion-likely evoked a representation of the value of the infusion and led to goal-directed behavior. These data indicate that abstinent cue-induced responding is multifaceted, dynamically engendering habitual or goal-directed behavior. Moreover, since goal-directed behavior terminated habitual behavior during testing, therapeutic approaches aimed at reducing the perceived value of cocaine in addicted individuals may reduce the capacity of cues to induce relapse

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Rationale Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. Objective The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Results Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Conclusions Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many \u201coff target\u201d effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence