A PERSPECTIVE ON THE FINANCIAL SITUATION IN AGRICULTURE

My purpose in this presentation is to give an overview or perspective on the financial situation in U.S. agriculture. Since descriptions of the situation are generally available (Easterbrook, J. Lee, Melichar-1985, ERS-USDA, van Blokland), I'll only briefly review the problem and its roots. The major emphasis of my presentation is devoted to two areas: difficulties in addressing current financial problems of the sector, and issues which deserve consideration for the future.Agricultural Finance,

INFLATION, CASH FLOWS, AND GROWTH: SOME IMPLICATIONS FOR THE FARM FIRM

Agribusiness,

Meeting the Need: A Summary and Evaluation of Ny Farmnet

A.E. Res. 91-3New York FarmNet, a state supported, toll-free, phone help-line for farmers began in March 1986 in response to the farm financial crisis. Its purpose included providing information/refelTal, individualized business/financial analysis and a general safety net for farm families, From March 1986 through March 1991 FmmNet received 3853 calls and assigned 534 consultants to work one-to-onc with fm'm families experiencing severe problems. A summm'y of caller characteristics revealed that slightly over half of callers were males, and nearly all were owners or operators rather than farm workers. Each year caller fmm size averaged between 230 and 320 acres, but the range was from one acre to over 4000 acres. Years of fm'ming experience each year averaged 16 to 23 years, but the range was from I yem' or less to a lifetime. Average debt of callers each yem' averaged between $100,000 and$200,000, and several callers reported debt of over $1,000,000. The main reasons for calling FarmNet were financial or financial/legal problems, but many other reasons were given including need for job information and emotional stress, A 1990-91 phone survey sampled people who had called FarmNet in 1986-87. The survey asked about their recollections of help received from FarmNet. They were generally positive on the helpfulness of the phone operators and remembered considering a number of options as a result of a FarmNet consultant visit. About one third of those callers is no longer fm'ming, and one fifth is in a different type of farming than in 1986-87. Based on five years of the program, several conclusions were offered. 1) A segment of the fm'm population is likely to be at risk each yem'; hence, there is a continuing need for addressing such problems; 2) FarmNet served an audience that would not have been reached by previously existing programs; 3) FarmNet's accomplishments went beyond just focusing on problems of callers to build expertise within Cornell Cooperative Extension staff and networking with other agencies and help sources; 4) The program achieved a positive image under the difficult circumstances of sometimes being the messenger of bad news; and 5) individualized, demand-driven programs such as FarmNet require difficult policy choices in these times of tight budgets

In silico modeling indicates the development of HIV-1 resistance to multiple shRNA gene therapy differs to standard antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Gene therapy has the potential to counter problems that still hamper standard HIV antiretroviral therapy, such as toxicity, patient adherence and the development of resistance. RNA interference can suppress HIV replication as a gene therapeutic via expressed short hairpin RNAs (shRNAs). It is now clear that multiple shRNAs will likely be required to suppress infection and prevent the emergence of resistant virus.</p> <p>Results</p> <p>We have developed the first biologically relevant stochastic model in which multiple shRNAs are introduced into CD34+ hematopoietic stem cells. This model has been used to track the production of gene-containing CD4+ T cells, the degree of HIV infection, and the development of HIV resistance in lymphoid tissue for 13 years. In this model, we found that at least four active shRNAs were required to suppress HIV infection/replication effectively and prevent the development of resistance. The inhibition of incoming virus was shown to be critical for effective treatment. The low potential for resistance development that we found is largely due to a pool of replicating wild-type HIV that is maintained in non-gene containing CD4+ T cells. This wild-type HIV effectively out-competes emerging viral strains, maintaining the viral <it>status quo</it>.</p> <p>Conclusions</p> <p>The presence of a group of cells that lack the gene therapeutic and is available for infection by wild-type virus appears to mitigate the development of resistance observed with systemic antiretroviral therapy.</p

Structural changes in commercial agriculture

The basic idea of the conference on Structural Changes in Commercial Agriculture was planted in the spring of 1964 by Earl 0. Heady. He outlined for the North Central Farm Management Research Committee his concern about the kind and amount of response to both current and prospective structural changes in the commercial farm firm. Many changes represent adjustments to technological and other innovations originating in marketing, research, and educational agencies serving farmers.https://lib.dr.iastate.edu/card_reports/1025/thumbnail.jp

High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults: A Phase II Open-Label Randomized Controlled Trial.

BACKGROUND: High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. METHODS: In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration, and grade 3-5 adverse events. RESULTS: We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/µL (interquartile range [IQR] 46-56). On day 2, geometric mean plasma AUC0-24hr was 42.9·h mg/L with standard-of-care 10 mg/kg dosing, 249·h mg/L for IV-20 and 327·h mg/L for PO-35 (P < .001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2-2.5) for IV-20 and 2.17 mg/L (1.6-2.9) for PO-35 regimens (P < .001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P = .34). CONCLUSIONS: Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures ~6- and ~8-fold higher than standard of care, and CSF levels above the MIC

High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)

Background: Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), results in death or neurological disability in &gt;50%, despite World Health Organisation recommended therapy. Current TBM regimen dosages are based on data from pulmonary TB alone. Evidence from recent phase II pharmacokinetic studies suggests that high dose rifampicin (R) administered intravenously or orally enhances central nervous system penetration and may reduce TBM associated mortality. We hypothesize that, among persons with TBM, high dose oral rifampicin (35 mg/kg) for 8 weeks will improve survival compared to standard of care (10 mg/kg), without excess adverse events. Protocol: We will perform a parallel group, randomised, placebo-controlled, double blind, phase III multicentre clinical trial comparing high dose oral rifampicin to standard of care. The trial will be conducted across five clinical sites in Uganda, South Africa and Indonesia. Participants are HIV-positive or negative adults with clinically suspected TBM, who will be randomised (1:1) to one of two arms: 35 mg/kg oral rifampicin daily for 8 weeks (in combination with standard dose isoniazid [H], pyrazinamide [Z] and ethambutol [E]) or standard of care (oral HRZE, containing 10 mg/kg/day rifampicin). The primary end-point is 6-month survival. Secondary end points are: i) 12-month survival ii) functional and neurocognitive outcomes and iii) safety and tolerability. Tertiary outcomes are: i) pharmacokinetic outcomes and ii) cost-effectiveness of the intervention. We will enrol 500 participants over 2.5 years, with follow-up continuing until 12 months post-enrolment. Discussion: Our best TBM treatment still results in unacceptably high mortality and morbidity. Strong evidence supports the increased cerebrospinal fluid penetration of high dose rifampicin, however conclusive evidence regarding survival benefit is lacking. This study will answer the important question of whether high dose oral rifampicin conveys a survival benefit in TBM in HIV-positive and -negative individuals from Africa and Asia. Trial registration: ISRCTN15668391 (17/06/2019