Search

Over the past decade, the incidence of primary and secondary syphilis has increased dramatically in the United States and western Europe. Men living with HIV and those at risk of HIV infection experience disproportionately high rates of early syphilis [ES]. We compared the odds of ES among HIV-positive and HIV-negative men participating in a status-neutral comprehensive HIV prevention and treatment program [CHP].We conducted a retrospective analysis of men aged 18-65 years with ≥ one CHP visit and ≥ two rapid plasma reagin [RPR] tests performed between January 1, 2018, and December 31, 2021. ES was defined as newly reactive RPR with a minimum titer of ≥1:4 or a ≥ four-fold increase in the RPR titer. Multiple logistic regression analyses were performed to determine predictors of ES.A total of 2490 men met the inclusion criteria, of whom 1426 (57·3%) were HIV-positive and 1064 (42·7%) were HIV-negative. Of the 393 men with ES, 284 (72·3%) were HIV-positive and 109 (27·7%) were HIV-negative. HIV-positive men had higher adjusted odds of ES (aOR 2·86, 95% CI 2·45, 3·27) than HIV-negative men did. Chlamydia or gonorrhea [CTGC] infection did not differ according to HIV status (aOR 0·93, 95% CI 0·82, 1·04).In our status-neutral care setting, HIV-positive status was associated with significantly higher odds of ES, but not CTGC. Our findings emphasize the vulnerability of HIV-positive men to syphilis in an era of effective HIV biomedical prevention.

Oral metronomic topotecan represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib in targeting angiogenesis. A phase I and pharmacokinetic (PK) study of this combination was performed in children with relapsed/refractory solid tumors. Oral topotecan and pazopanib were each administered daily without interruption in 28-day cycles at five dose levels (0.12 to 0.3 mg/m2 topotecan and 125 to 160 mg/m2 pazopanib powder for oral suspension (PfOS)), with dose escalation in accordance with the rolling-six design. PK studies were performed on day 1 and at steady state. Thirty patients were enrolled, with 26 evaluable for dose-limiting toxicity (DLT), with median age 12 years (3–20). Toxicities were generally mild; the most common grade 3/4 adverse events related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphopenia (11%), AST elevation (11%), and lipase elevation (11%). Only two cycle 1 DLTs were observed on study, both at the 0.3/160 mg/m2 dose level comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle 1 required treatment discontinuation. The best response was stable disease in 10/25 patients (40%) for a median duration of 6.4 (1.7–45.1) months. The combination of oral metronomic topotecan and pazopanib is safe and tolerable in pediatric patients with solid tumors, with a recommended phase 2 dose of 0.22 mg/m2 topotecan and 160 mg/m2 pazopanib. No objective responses were observed in this heavily pre-treated patient population, although 40% did achieve stable disease for a median of 6 months. While this combination is likely of limited benefit for relapsed disease, it may play a role in the maintenance setting.

In this chapter we examine a project called the Commission on Social Security, led by Experts by Experience (hereafter, ‘the Commission’). The aim of the project is to produce a White Paper style document on social security, setting out policy proposals for a better benefits system. The project takes a ground-breaking approach with all the Commissioners being people with lived experience of the social security system i.e. current or recent benefit claimants (referred to as ‘Experts by Experience’, the term having been decided on by the people with lived experience who became involved in the project).

Objective This study aimed to validate a novel, three faced, colour-coded, action-oriented tool: The Stoplight Pain Scale (SPS). Methods A prospective observational cohort study was conducted at a Canadian paediatric emergency department from November 2014 to February 2017. Patients aged 3 to 12 years and their caregivers were asked to rate pain using the SPS and the Faces Pain Scale-Revised (FPS-R). Pain was measured just before analgesia administration, 30 minutes after analgesia administration, and immediately following a painful procedure. Results A total of 227 patients were included; 26.9% (61/227) were 3 to 5 years old while 73.1% (166/227) were 6 to 12 years old. Using Cohen’s κ, agreement for SPS and FPS-R was ‘fair’ for children (0.28 [95% confidence interval {CI} 0.20 to 0.36]) and ‘poor’ for caregivers (0.14 [95% CI 0.07 to 0.21]), at initial measurement. The SPS had ‘fair’ agreement between child and caregiver scores, (0.37 [95% CI 0.27 to 0.47]), compared to FPS-R which showed ‘poor’ agreement (0.20 [95% CI 0.12 to 0.29]). Absolute agreement between child and caregiver SPS scores improved with repeat exposure; 30 minutes after analgesia administration, caregivers and children had fair agreement (κ=0.38, 95% CI 0.28 to 0.48); they had moderate agreement directly following painful procedures (κ=0.46, 95% CI 0.34 to 0.59). Overall, 72.4% (139/192) of children and 60.2% (118/196) of caregivers preferred SPS over FPS-R. Conclusion The SPS demonstrates fair agreement with FPS-R for children and fair-moderate agreement between children and caregivers; agreement improved with repeat use. The SPS is simple and easy to use; it may have a role in empowering direct child and family involvement in pain management.

OBJECTIVES To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis. METHODS We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures. RESULTS Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively). CONCLUSIONS True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.

10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib (PZ) in targeting angiogenesis. This study was designed to determine the recommended phase 2 dose (RP2D) of mTP/PZ in pediatric patients with solid tumors, while describing the safety and toxicity of this regimen. Methods: A phase I dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) study of mTP/PZ was conducted at ten sites across Canada, enrolling pediatric patients aged 2-21 years with relapsed/refractory solid tumors. Patients were treated with oral mTP and PZ suspension daily without interruption in 28-day cycles, with dose escalation in accordance with the rolling-six design. Five dose levels (0.12/125, 0.16/125, 0.22/125, 0.22/160, and 0.3/160 mg/m2/day of mTP/PZ) were evaluated. PK studies were performed on day 1 and at steady state, and PD studies included circulating angiogenic factors VEGFR1, VEGFR2, VEGF, endoglin and placental growth factor. Results: Thirty patients (pts) were enrolled, of whom 26 were evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). The most common diagnoses included osteosarcoma (8), neuroblastoma (NB, 7), Ewing sarcoma/PNET (4), and rhabdomyosarcoma (4). The most common grade 3/4 adverse events (AEs) related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphocytopenia (11%), AST elevation (11%), and lipase elevation (11%). Only 2 cycle-1 DLTs were observed on study, both at the 0.3/160 mg/m2 mTP/PZ dose level (2/5 pts) comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle-1 required treatment discontinuation. Best response was stable disease in 10/25 pts (40%) for a median duration of 6.4 months (1.7-45.1). One patient with refractory NB achieved stable disease for 45 months and continued on mTP/PZ via compassionate access after study closure. PK and PD results are pending at this time. Conclusions: The combination of oral mTP and PZ is safe and tolerable in pediatric patients with solid tumors, with a RP2D of mTP 0.22 mg/m2/day and PZ suspension 160 mg/m2/day. Ten patients achieved stable disease for a median of 6 months. The lack of objective responses suggests that this combination is likely of limited benefit for relapsed disease, but may play a role as maintenance therapy. Clinical trial information: NCT02303028.

Proximal-type epithelioid sarcoma is an ultra-rare, high-grade soft tissue malignancy usually presenting as a deep-seated painless mass in the proximal extremities. Most patients are diagnosed as young adults, between 20 and 40 years of age. Perineal and genital masses do occur but are extremely rare and represent a challenging tumour to diagnose and treat. Early radical excision is recommended due to its aggressive behaviour and poor prognosis. Median overall survival from initial diagnosis is 30 months. We present the case of a 22-year-old man with a left groin proximal-type epithelioid sarcoma who is sadly deceased 12 months after initial presentation despite early surgical excision, completion of both first-line and palliative chemotherapy, and palliative radiotherapy.

Objectives The objective was to review the clinical outcomes of children with suspected appendicitis after an ultrasound (US) examination fails to fully visualize the appendix, the diagnostic characteristics of US in children with suspected appendicitis, and the predictive value of secondary signs of appendicitis when the appendix is not fully visualized. Methods This was a retrospective health record review of children aged 3 to 17 years presenting to a tertiary pediatric emergency department (ED) with suspected appendicitis. Descriptive statistics and diagnostic test characteristics are reported. Results Overall, 968 children had US. The appendix was fully visualized in 442 cases (45.7%), and 526 (54.3%) children had incompletely visualized appendices. The disposition of those with incompletely visualized appendices were as follows: 59.1% were discharged home, 10.5% went directly to the operating room, and 30.4% were admitted to the hospital for further observation. Of those discharged home based on clinical findings after incompletely visualized appendices, fewer than 0.3% ended up having appendicitis. Ultimately 15.6% of children with incompletely visualized appendices had pathology-confirmed appendicitis. The sensitivity and specificity of US for children with fully visualized appendices were 99.5% (95% confidence interval [CI] = 96.7% to 100%) and 81.3% (95% CI = 75.2% to 86.2%), respectively. The sensitivity and specificity for the presence of any secondary sign in diagnosing appendicitis were 40.2% (95% CI = 29.6% to 51.7%) and 90.6% (95% CI = 87.5% to 93.2%), respectively. Conclusions Children with incompletely visualized appendices on US can be safely discharged home based on clinical findings with an acceptable rate of missed appendicitis. Children with nonreassuring clinical examinations following incompletely visualized appendices on US may benefit from further imaging studies prior to appendectomy, to reduce the rate of negative appendectomy. While the presence of secondary signs of inflammation can be used to rule in appendicitis, statistical strength to rule out appendicitis in the absence of secondary signs is insufficient. Resumen Objetivos Revision de los resultados clinicos de los ninos con sospecha de apendicitis tras un examen ecografico fallido en la visualizacion completa del apendice. Se revisaron tambien las caracteristicas diagnosticas ecograficas en ninos con sospecha de apendicitis, y el valor predictivo de los signos secundarios de apendicitis cuando el apendice no es visualizado totalmente. Metodologia Revision retrospectiva de las historias clinicas de los ninos entre 3 y 17 anos que acudieron a un servicio de urgencias (SU) pediatrico de nivel terciario con sospecha de apendicitis. Se documentaron los estadisticos descriptivos y las caracteristicas de las pruebas diagnosticas. Resultados A un total de 968 ninos se les realizo una ecografia. El apendice se visualizo completamente en 442 casos (45,7%), y en 526 (54.3%) de forma incompleta. La ubicacion de aquellos con una visualizacion incompleta ecografica fue la siguiente: un 59,1% fueron dados de alta a domicilio, un 10,5% fue directamente al quirofano y un 30,4% fue ingresado en el hospital para mayor observacion. Entre aquellos dados de alta a domicilio en base a los hallazgos clinicos tras una visualizacion incompleta ecografica, menos de un 0,3% acabaron teniendo una apendicitis. Finalmente, un 15,6% de los ninos con visualizacion incompleta tuvo apendicitis confirmada anatomopatologicamente. La sensibilidad y la especificidad de la ecografia para ninos con visualizacion completa del apendice fuer on de un 99,5% (intervalo de confianza [IC] 95% = 96,7% a 100%), y un 81,3% (IC 95% = 75,2% a 86,2%), respectivamente. La sensibilidad y especificidad para la presencia de cualquier signo secundario en el diagnostico de apendicitis fue ron de un 40,2% (IC 95% = 29,6% a 51,7%) y un 90,6% (IC 95% = 87,5% a 93,2%), respectivamente. Conclusiones Los ninos con una visualizacion incompleta del apendice en la ecografia pueden ser dados de alta al domicilio de forma segura basandose en los resultados clinicos con un porcentaje aceptable de apendicitis no diagnosticadas. Los ninos con exploraciones clinicas no tranquilizadoras tras una visualizacion incompleta del apendice en la ecografia pueden beneficiarse de otras pruebas de imagen previamente a la apendicectomia, para reducir el porcentaje de apendicectomias negativas. Mientras que la presencia de signos secundarios de inflamacion puede utilizarse para diagnosticar la apendicitis, la potencia estadistica para descartar la apendicitis en ausencia de signos secundarios es insuficiente.

During an investigation of an outbreak of gastroenteritis caused by Salmonella enterica serovar Paratyphi B variant L(+) tartrate(+), we identified unpasteurized tempeh as a novel food vehicle and Rhizopus spp. starter culture as the source of the contamination. Safe handling of uncooked, unpasteurized tempeh should be emphasized for prevention of foodborne illnesses.

In humans, the SLC28 concentrative nucleoside transporter (CNT) protein family is represented by three Na+-coupled members; human CNT1 (hCNT1) and hCNT2 are pyrimidine and purine nucleoside-selective, respectively, whereas hCNT3 transports both purine and pyrimidine nucleosides and nucleoside drugs. Belonging to a phylogenetic CNT subfamily distinct from hCNT1/2, hCNT3 also mediates H+/nucleoside cotransport. Using heterologous expression in Xenopus oocytes, we have characterized a cysteineless version of hCNT3 (hCNT3C-). Processed normally to the cell surface, hCNT3C-exhibited hCNT3-like transport properties, but displayed a decrease in apparent affinity specific for Na+ and not H+. Site-directed mutagenesis experiments in wild-type and hCNT3C-backgrounds identified intramembranous Cys-561 as the residue responsible for this altered Na+-binding phenotype. Alanine at this position restored Na+ binding affinity, whereas substitution with larger neutral amino acids (threonine, valine, and isoleucine) abolished hCNT3 H+-dependent nucleoside transport activity. Independent of these findings, we have established that Cys-561 is located in a mobile region of the hCNT3 translocation pore adjacent to the nucleoside binding pocket and that access of p-chloromercuribenzene sulfonate to this residue reports a specific H+-induced conformational state of the protein (Slugoski, M. D., Ng, A. M. L., Yao, S. Y. M., Smith, K. M., Lin, C. C., Zhang, J., Karpinski, E., Cass, C. E., Baldwin, S. A., and Young, J. D. (2008) J. Biol. Chem.283 ,8496 -850718199742). The present investigation validates hCNT3C- as a template for substituted cysteine accessibility method studies of CNTs and reveals a pivotal functional role for Cys-561 in Na+- as well as H+-coupled modes of hCNT3 nucleoside transport.

Background Ondansetron is often used in the emergency department (ED) to promote oral rehydration in children with acute gastroenteritis (AGE), yet medication solutions administered orally may be poorly tolerated in this population. Objectives We compared the tolerability of ondansetron oral dissolve tab (ODT) to oral solution (OS) in children presenting to the ED with AGE. Methods Using alternate-day controlled clinical trial design, children aged 3 months to 10 years received either ondansetron ODT or OS. Our primary outcome was early vomiting (within 15 min of drug administration). The secondary outcome was intravenous (i.v.) fluid administration. Results There were 462/534 eligible children who met study criteria. Demographics, severity, and duration of illness were similar between groups. Using intention-to-treat analysis, early vomiting occurred in 8/209 ODT vs. 19/253 OS children (3.8% vs. 7.5%; odds ratio [OR] 0.49; 95% confidence interval [CI] 0.18–1.21). Using as-treated analysis, 6/222 (2.7%) children receiving ODT experienced early vomiting, compared with 21/221 (9.5%) of the OS group (OR 0.26; 95% CI 0.09–0.70). The proportion of children discharged without i.v. fluids was not different ( intention-to-treat : ODT = 91.4% (191/209), OS = 94.1% (238/253), OR 1.49, 95% CI 0.69–3.28; as-treated: ODT = 92.3% (205/222), OS = 93.2% (206/221), OR 0.88, 95% CI 0.40–1.93). Conclusions Using a conservative intention-to-treat analysis, we found that children presenting to an ED with AGE did not have statistically less early vomiting with ondansetron ODT as compared with OS. However, our as-treated analysis demonstrates that children receiving ondansetron ODT experienced early vomiting approximately one-third as often as those receiving OS. The rate of i.v. fluid administration was no different between groups regardless of the type of analysis used.

The in vitro effect of combinations of the Penicillium mycotoxins citrinin (CIT), cyclopiazonic acid (CPA), ochratoxin A (OTA), patulin (PAT), penicillic acid (PIA) and roquefortine C (RQC) on mitogen induced lymphocyte proliferation was determined using purified lymphocytes from six piglets. Dose-response curves for each mycotoxin and mycotoxin combinations were generated. The combined effects of toxin pairs based on IC20 were illustrated in isobole diagrams and statistically calculated. OTA and CIT elicited a synergistic effect. Four toxin pairs elicited additive effects, four pairs less-than-additive effects and six pairs independent effects. Thus, the majority of toxin pairs tested produced lower combined effects than an additive effect. The results indicate that the sum effect of all toxins is less than that from the summation of concentrations of the individual compounds, adjusted for differences in potencies.

The secondary metabolites of 24 isolates of Fusarium avenaceum from Norwegian cereals and grown on rice have been characterized. Moniliformin (MON), enniatins (ENNs), and beauvericin (BEA) were analyzed by high-performance liquid chromatography. Porcine kidney epithelial cells (PK15, American Type Culture Collection) were used to study the cytotoxicity of MON in the extracts. The following metabolites were produced by all isolates, ranked by concentration in rice cultures: ENN-B, MON, ENN-B1, and ENN-A. BEA was produced by eight isolates. The productions of BEA and ENN-A were significantly correlated, as was the case with ENN-B and ENN-B1. MON production was correlated neither to any of the other toxins nor to toxicity.

The cytotoxicity and secondary metabolites of 28 Norwegian strains of Fusarium equiseti have been characterized. Trichothecenes and fusarochromanone (FUCH) in rice culture extracts of the strains were analysed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). The following metabolites were found in all isolates: FUCH, nivalenol (NIV), scirpentriol (SCIRP), 4-acetylnivalenol (4-ac-NIV, also called fusarenon-X), 15-acetyl-nivalenol (15-ac-NIV), and diacetoxyscirpenol (DAS). 4,15-diacetyl-nivalenol (diacetyl-NIV) was found in 5 isolates. Porcine kidney epithelial cells (PK15, American Type Culture Collection) were exposed to rice culture extracts to study cytotoxicity. Descriptive statistics and factor analysis of the identified secondary metabolites show that their main metabolites were FUCH, NIV, SCIRP, DAS and 15-ac-NIV, consecutively. The individual trichothecenes were highly intercorrelated, whereas the production of acetylated NIV and DAS was slightly less. Stepwise multiple regression analysis of cytotoxicity and metabolite profiles of rice culture extracts ascribed the toxicity mainly to a combination of FUCH and 15-ac-NIV, though SCIRP or DAS are agents in the combined toxicity as well.

Mycotoxins are naturally occurring toxic secondary metabolites of fungi that may be present in food and feed. Several of these mycotoxins have been associated with human and animal diseases. Fusarium species, found worldwide in cereals and other food types for human and animal consumption, are the most important toxigenic fungi in northern temperate regions. The overall economical loss and the detrimental health effects in humans and animals of mycotoxin contamination are enormous and therefore, rapid screening methods will form an important tool in the protection of humans and animals as well as to minimize economical losses by early detection. An overview of methods for the determination of cytotoxicity and the application of such bioassays to screen solid fungal cultures, cereals, respectively, food/feedstuffs for the presence and toxic potential of Fusarium mycotoxins is presented. Various cell lines including different endpoints of toxicity using vertebrate cells and the predictive value of the in vitro assays are reviewed. Bioassays are compared with existing chemical analytical methods and the possibilities and limitations of such systems are discussed. The review is based on 149 references.

Lythrum salicaria L., purple loosestrife, an invasiveEurasian perennial, is degrading wetlands across temperate NorthAmerica. Chemical, physical, and mechanical methods failed to providelong-term control. Therefore, four host-specific insect species (twoleaf feeders, a root feeder, and a flower feeder) were introduced asbiological control agents. To increase the availability of adults ofthe root feeding weevil Hylobius transversovittatus Goezefor field releases, we developed a semiartificial diet. Suitability ofdifferent diet formulations (varying vitamin mixes, salt mixes,antimicrobials, water content, root content) and temperatures forlarval development were evaluated. We also monitored how rearing onartificial diet and the number of larvae per container affected larvaldevelopment time, larval survival, adult weight, and incidences ofdeformities. Rearing larvae on artificial diet reduced development timefrom 1–2 yr to 2–3 mo. Larval development was fastest and survivalrates highest under consta...

The in vitro effect of each of the Penicillium mycotoxins citrinin (CIT), cyclopiazonic acid (CPA), ochratoxin A (OTA), patulin (PAT), penicillic acid (PIA) and roquefortine C (RQC) on mitogen induced lymphocyte proliferation was determined using purified lymphocytes from 6 piglets. Dose response curves for each mycotoxin were generated and the concentrations producing 50% inhibition of cell proliferation (IC(50)) were estimated. OTA and PAT were the most potent toxins with IC(50) of 1.3 and 1.2 micromol/l, respectively (0.52 and 0.18 mg/l, respectively). Based on molar concentrations, OTA was 15, 30, 40, and 65 times more potent as an inhibitor than PIA, CIT, CPA and RQC, respectively.

The cytotoxicity and secondary metabolites of 28 Norwegian strains of Fusarium equiseti have been characterized. Trichothecenes and fusarochromanone (FUCH) in rice culture extracts of the strains were analysed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). The following metabolites were found in all isolates: FUCH, nivalenol (NIV), scirpentriol (SCIRP), 4-acetylnivalenol (4-ac-NIV, also called fusarenon-X), 15-acetyl-nivalenol (15-ac-NIV), and diacetoxyscirpenol (DAS). 4,15-diacetyl-nivalenol (diacetyl-NIV) was found in 5 isolates. Porcine kidney epithelial cells (PK15. American Type Culture Collection) were exposed to rice culture extracts to study cytotoxicity. Descriptive statistics and factor analysis of the identified secondary metabolites show that their main metabolites were FUCH, NIV, SCIRP, DAS and 15-ac-NIV, consecutively. The individual trichothecenes were highly intercorrelated, whereas the production of acetylated NIV and DAS was slightly less. Stepwise multiple regression analysis of cytotoxicity and metabolite profiles of rice culture extracts ascribed the toxicity mainly to a combination of FUCH and 15-ac-NIV, though SCIRP or DAS are agents in the combined toxicity as well.

A method is described, by wich the malolactic fermentation is induced through direct inoculation with an industrial preparation of L. plantarum (CHL2). When inoculated into must, this homofermentative lactobacillus metabolizes very little sugar, and is unable to produce acetic acid. The inoculated population of bacteria has a high malolactic activity even at low pH values, which is closely related to cell viability. The decarboxylation of malic acid starts immediately after inoculation and proceeds at a high rate during the first days of alcoholic fermentation. As the alcohol concentration rises, the lactobacilli are gradually eliminated, so inoculation with the malolactic culture has to be done very early in the vinification process, in order to achieve a complete malolactic fermentation. At the end of alcoholic fermentation, the malolactic fermentation is finished, and the bacterial inoculum has been completely killed of.The efficiency of this new process is demonstrated in laboratory experiments and field trials with different types of must and different vinification procedures. The advantages of the method, which the winemakers would particularly appreciate, include the direct inoculation mode and considerable gain in terms of production time.