Molecular signatures of cortical expansion in the human fetal brain.

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. A growing catalogue of cells in the prenatal brain has revealed remarkable molecular diversity across cortical areas.1,2 Despite this, little is known about how this translates into the patterns of differential cortical expansion observed in humans during the latter stages of gestation. Here we present a new resource, µBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal developing brain. Built using generative artificial intelligence, µBrain is a three-dimensional cellular-resolution digital atlas combining publicly-available serial sections of the postmortem human brain at 21 weeks gestation3 with bulk tissue microarray data, sampled across 29 cortical regions and 5 transient tissue zones.4 Using µBrain, we evaluate the molecular signatures of preferentially-expanded cortical regions during human gestation, quantified in utero using magnetic resonance imaging (MRI). We find that differences in the rates of expansion across cortical areas during gestation respect anatomical and evolutionary boundaries between cortical types5 and are founded upon extended periods of upper-layer cortical neuron migration that continue beyond mid-gestation. We identify a set of genes that are upregulated from mid-gestation and highly expressed in rapidly expanding neocortex, which are implicated in genetic disorders with cognitive sequelae. Our findings demonstrate a spatial coupling between areal differences in the timing of neurogenesis and rates of expansion across the neocortical sheet during the prenatal epoch. The µBrain atlas is available from: https://garedaba.github.io/micro-brain/ and provides a new tool to comprehensively map early brain development across domains, model systems and resolution scales.

Risk factors for KPC-producing Enterobacteriaceae acquisition and infection in a healthcare setting with possible local transmission: a case-control study.

BACKGROUND: Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) in Australia were previously uncommon, with cases imported sporadically by travellers from higher prevalence countries. AIM: The study institution reported the first outbreak of KPC-Kp in Australia. The aim of this study was to identify risk factors for KPC-Kp colonization and infection using a matched case-control study. METHODS: The study included all hospitalized patients with KPC-Kp colonization or infection from January 2012 to September 2015. FINDINGS: Thirty-four cases of KPC-producing Enterobacteriaceae (including 31 KPC-Kp cases) were matched with 136 controls. Variables associated with KPC-Kp acquisition included: length of hospital stay >28 days in the past 12 months, prior vancomycin-resistant enterococci (VRE) colonization, central venous catheter (CVC), gastrointestinal disease and invasive procedures. Exposure to broad-spectrum antibiotics was also found to be a significant risk factor. In the multi-variate analysis, three factors independently associated with KPC-Kp acquisition were length of hospital stay >28 days in the past 12 months [odds ratio (OR) 23.6, 95% confidence interval (CI) 4.9-113.3], presence of a CVC (OR 15.4, 95% CI 2.7-86.9), and prior VRE colonization (OR 6.0, 95% CI 1.6-23.2). Very few patients had a history of overseas travel. CONCLUSION: This study demonstrates that patients with prolonged hospital exposure are more likely to acquire KPC-Kp in the setting of a local outbreak, and suggests that risk factors for KPC-Kp acquisition may be shared with those for VRE colonization. Local screening strategies targeting overseas travellers would likely miss many cases. The results of this study will help to inform screening policies for carbapenemase-producing Enterobacteriaceae.

E. coli bacteremia in comparison to K. pneumoniae bacteremia: influence of pathogen species and ESBL production on 7-day mortality.

In a previous study, we demonstrated prolonged length of hospital stay in cases of extended-spectrum beta-lactamase (ESBL)-positive K. pneumoniae bacteremia compared to bacteremia cases due to E. coli (ESBL-positive and -negative) and ESBL-negative K. pneumoniae. The overall mortality was significantly higher in bacteremia cases resulting from ESBL-positive pathogens but also in K. pneumoniae cases disregarding ESBL-production. In order to examine whether pathogen species rather than multidrug resistance might affect mortality risk, we reanalyzed our dataset that includes 1.851 cases of bacteremia.

Male mate preference and size-assortative mating in convict cichlids: A role for female aggression?

Many monogamous species demonstrate size-assortative mating patterns within natural populations. To better understand the role of intersexual selection in this process, we examined the effect of male preference for female body size in the convict cichlid (Amatitlania siquia). We provided males with a choice between females that differed in size, relative to each other and in relation to the focal male. Based on previous work, we expected males to prefer the largest available female mates across all treatments. Surprisingly, males spent more time near the smaller of two available females, but only when the other female was larger than the male. Additionally, males spent little time with either of two potential female mates when both females were larger than the male. We hypothesized that while males might prefer the largest of available females, female behavior might limit males from acting on this preference. To test this, males were force paired with a smaller or larger female. Pair formation only occurred when the female was smaller than the male, and females that were larger than their male counterparts showed significantly more aggression when compared to smaller females. Together, these data suggest that in the absence of intrasexual competition, male mate preference for large females in convict cichlids might be limited by female aggression.

[Economic Analysis of Treatment Courses for Patients Over the Age of 80 Years at a Surgical Maximum Care Centre]. / Ökonomische Analyse des Behandlungsverlaufs bei über 80-jährigen Patienten an einer Klinik der chirurgischen Maximalversorgung.

BACKGROUND: The demographic change in Germany with an aging population and the resulting necessity of adequate surgical care for older patients was lately discussed with concern. One major aspect is the estimated higher treatment costs in the care of the elderly. MATERIALS AND METHODS: InEK data from all cases of patients over the age of 80, who were treated and discharged from 2008 to 2012 as inpatients at the Department of General, Visceral, Vascular and Thoracic Surgery at the Charité - Universitätsmedizin Berlin, Campus Mitte, were analysed. Of a total of 13,612 patients 626 patients were over the age of 80. Their lengths of stay, mode of discharge and discharge management as well as costs and reimbursements according to the relevant diagnosis-related groups were analysed. RESULTS: Cases of elderly patients amounted to a stable 5 % of all cases from 2008 until 2012. Their mean length of stay was 14 (median, 9), range, 1-129 days. 80 % of patients could be regularly discharged, 9 % died, 8 % were transferred to another hospital, 2 % discharged into a nursing home and 1 % into a rehabilitation centre. The elderly patients had a patient clinical complexity level of mean 2.84. Costs per day amounted to a mean 778 (median: 627) €, range: 306-7740 €, total costs to 10,686 (median: 5140) €, range: 368-186,059 €. The mean deficit was 491 (median: 176) € per patient, range: - 30,470-75,144 €. The discharge management was significantly different in comparison to patients under the age of 80 with respect to avoidance of discharge at the weekend. CONCLUSION: Patients over the age of 80 are a relevant group in surgery. They have an increased perioperative risk, but patients should not be denied surgery solely because of their age. The perioperative management of the elderly has to be of maximum standardised quality. From an economic perspective it can be stated that elderly patients currently pose no exceptional financial risk to a surgical department, but contribute relevantly to the turnover, whereby special attention has to be paid to an early structured discharge management.

Bloodstream infection due to extended-spectrum beta-lactamase (ESBL)-positive K. pneumoniae and E. coli: an analysis of the disease burden in a large cohort.

PURPOSE: The burden of extended-spectrum beta-lactamase (ESBL)-positive Enterobacteriaceae (ESBL-E) is growing worldwide. We aimed to determine the financial disease burden attributable to ESBL-positive species in cases of bloodstream infection (BSI) due to K. pneumoniae and E. coli. METHODS: We conducted a cohort study on patients with BSI due to K. pneumoniae or E. coli between 2008 and 2011 in our institution. Data were collected on true hospital costs, length of stay (LOS), basic demographic parameters, underlying diseases as Charlson comorbidity index (CCI) and ESBL positivity of the pathogens. Multivariable regression analysis on hospital costs and length of stay was performed. RESULTS: Overall we found 1,851 consecutive cases of ESBL-E BSI, 352 (19.0%) cases of K. pneumoniae BSI and 1,499 (81.0%) cases of E. coli BSI. Sixty-six of E. coli BSI (18.8%) and 178 of K. pneumoniae BSI (11.9%) cases were due to ESBL-positive isolates, respectively (p = 0.001). 830 (44.8%) cases were hospital-onset, 215 (61.1%) of the K. pneumoniae and 615 (41.0%) of the E. coli cases (p < 0.001). In-hospital mortality was overall 19.8, 25.0% in K. pneumoniae cases and 18.5% in E. coli cases (p = 0.006). Increased hospital costs and length of stay were significantly associated to BSI with ESBL-positive K. pneumoniae. CONCLUSION: In contrast to BSI due to ESBL-positive E. coli, cases of ESBL-positive K. pneumoniae BSI were associated with significantly increased costs and length of stay. Infection prevention measures should differentiate between both pathogens.

Costs and prolonged length of stay of central venous catheter-associated bloodstream infections (CVC BSI): a matched prospective cohort study.

PURPOSE: Central venous catheter-associated bloodstream infections (CVC BSI) are a common and serious complication among critically ill patients on intensive care units (ICUs), but also result in a financial burden for the health care system. Our aim was to determine the additional costs and length of stay (LOS) of patients with ICU-acquired CVC BSI. METHODS: We used the surveillance method of the German nosocomial infection surveillance system (Krankenhaus Infections Surveillance System, KISS) to find cases of CVC BSI. The associated costs of CVC BSI were estimated as true costs generated within our hospital. We used a matched cohort design, comparing patients with CVC BSI and patients without BSI. The study period was from January to December 2010. Patients were matched by age, sex, and Simplified Acute Physiology Score (SAPS). The LOS in the ICU of control patients needed to be at least as long as that of CVC BSI patients before the onset of CVC BSI. RESULTS: We matched 40 CVC BSI patients to 40 patients without BSI. The median hospital costs for CVC BSI patients were significantly higher than for patients without BSI (60,445 € vs. 35,730 €; p = 0.006) and the CVC BSI patients stayed longer in the hospital than patients without CVC BSI (44 days vs. 30 days; p = 0.110). The median attributable costs per CVC BSI was 29,909 € (p = 0.006) and the median attributable LOS was 7 days (p = 0.006). CONCLUSION: CVC BSI is associated with increased hospital costs and prolonged hospital stay. Hospital management should implement control measurements to keep the incidence of CVC BSI as low as possible.

Novel use of the wild species Cephalaria joppensis for silage preparation and its nutritive value for feeding lactating dairy cows.

This study presents a novel method for use of the wild plant species Cephalaria joppensis (CJ) as agricultural forage for ruminants. Domesticated CJ tends to have higher crop mass yield per hectare than a commercial wheat variety (W) but is similar in in vitro dry matter (DM) digestibility. This study was composed of 3 experiments. Experiment 1 aimed to measure effects of ensiling CJ versus W in packed polyethylene-wrapped bales. Three types of ensiled bales were produced for each plant: 1) direct-cut CJ versus W packed solely; 2) direct-cut CJ versus W mixed as sole roughage source together with dietary ingredient and packed in bales to create CJ total mixed ration (CJ-TMR) or W-TMR; 3) CJ silage versus W silage mixed as one-third of dietary roughage source together with two-thirds sorghum (S) silage and additional dietary ingredients and packed in bales to create CJ-S-TMR or W-S-TMR. Data showed that packing and wrapping created anaerobic conditions within the 4 types of TMR bales while reducing pH (4.12 to 4.37). Dry matter loss during ensilage was higher for the 2 types of TMR containing W compared with CJ. Ensilage decreased soluble nitrate content as well as yeast and mold contamination, and the 4 types of TMR bales were characterized by a long outdoor shelf life (3 mo) and high stability under aerobic exposure. Experiment 2 aimed to measure the intake and digestibility by sheep of the 4 types of packed TMR after 90 d of ensiling. Data demonstrated higher voluntary intake of the CJ-TMR compared with the other TMR types. The CJ-TMR was characterized by higher digestibility of DM, crude protein, and neutral detergent fiber components compared with the CJ-S-TMR. Experiment 3 examined intake, digestibility, and milk production by 21 pairs of lactating cows individually fed CJ-S-TMR versus W-S-TMR. Similar intake (21.6 to 22.0 kg/d) and digestibility of DM and crude protein were observed in cows fed the 2 TMR types (68 to 69% and 66 to 68%, respectively). However, neutral detergent fiber and cellulose digestibility were slightly higher in the cows fed W-S-TMR and this was reflected in a small increase in their milk and energy-corrected milk yield (36.5 and 31.4 kg/cow per day, respectively) compared with cows fed CJ-S-TMR (35.5 and 30.4 kg/cow per day, respectively). Results demonstrate that direct-cut CJ used as is, or CJ silage can be included and ensiled in TMR bales for feeding productive ruminants as a substitute for wheat silage.

Selective neurogenic blockade and perioperative immune reactivity in patients undergoing lung resection.

OBJECTIVE: This double-blind, prospective, randomized, controlled trial examined the effects of thoracic epidural block and intravenous clonidine and opioid treatment on the postoperative Th1/Th2 cytokine ratio after lung surgery. The primary endpoint was the interferon γ (IFN-γ; Th1 cytokine)/interleukin 4 (IL-4; Th2 cytokine) ratio. Secondary endpoints were reductions in pain and incidence of pneumonia. METHODS: Sixty patients were randomized into three groups to receive remifentanil intravenously (remifentanil group, n=20), remifentanil and clonidine intravenously (clonidine group, n=20), or ropivacaine epidurally (ropivacaine group, n=20). Pain was assessed using a numerical rating scale (NRS). Cytokines were measured using a cytometric bead array. RESULTS: Patients in the ropivacaine group (thoracic epidural block) had a significantly lower IFN-γ/IL-4 ratio at the end of surgery than those in the remifentanil group and clonidine group. There were no significant between-group differences in the IFN-γ/IL-4 ratio at other time-points. There were no differences in NRS scores at any time-point. No patient developed pneumonia. CONCLUSION: Intraoperative thoracic epidural block decreased the IFN-γ/IL-4 ratio immediately after lung surgery, indicating less inflammatory stimulation during surgery.

Volume therapy and cardiocircular function during hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Surgical cytoreduction and simultaneous hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis is afflicted with a high incidence of postoperative complications. The knowledge of intraoperative volume therapy during surgery and chemotherapy is limited. On the other hand, the choice of a 'liberal' or 'restrictive' regimen of fluid administration has a deep impact on the postoperative morbidity. The aim of this observational trial was to report detailed data on volume replacement and cardiocircular function during the HIPEC procedure. METHODS: Eighteen consecutive patients undergoing cytoreductive surgery and HIPEC for peritoneal carcinomatosis were enrolled. The intraoperative volume administration was observed as well as the postoperative morbidity and mortality. Cardiofunctional data were assessed by the invasive transthoracic thermodilution technique. RESULTS: The study showed that large amounts of volume (1,240 ml h(-1); range: 810-1,570 ml h(-1)) are given during the HIPEC procedure to replace fluid loss and maintain a stable circulatory function. Signs of a hyperdynamic status during intraoperative intraperitoneal chemotherapy were not found. CONCLUSIONS: During surgical cytoreduction and simultaneous HIPEC, large amounts of volume were administered. HIPEC in itself did not lead to an increased fluid requirement. Further prospective studies with larger populations are needed to investigate whether goal-oriented therapies and a restricted volume regimen can contribute to decrease the postoperative morbidity.

["Fast-track" rehabilitation in thoracic surgery. First experiences with a multimodal, interdisciplinary, and proven perioperative treatment course]. / "Fast-track-Rehabilitation" in der Thoraxchirurgie. Erste Erfahrungen mit einem interdisziplinären, multimodalen, beweisbegründeten und perioperativen Behandlungspfad.

OBJECTIVES: "Fast-track" rehabilitation is a multimodal perioperative treatment concept for accelerating postoperative recovery which has been already used successfully in visceral surgery. Of its use in thoracic surgery however, almost no data exist and the relevance of this concept for pulmonary operations is unknown. PATIENTS AND METHODS: In this prospective study we examined a new perioperative fast-track treatment concept for thoracic surgery and evaluated the results. This program employs detailed information of patients, intensive perioperative respiratory therapy, thoracic peridural analgesia, forced mobilization, and an early start of postoperative normal food intake. RESULTS: Fifty consecutive patients with benign or malignant diseases of the lung aged an average of 64 years (range 22-78) were operated on thoracoscopically (n=15) or with thoracotomy (n=35) and treated perioperatively using the fast-track program. All patients were mobilized beginning 4 h postoperatively and had normal food. The incidence of general postoperative complications was 0% in this study. Postoperative stay lasted 4.5 days (range 1.5-28.5). There was no increase in surgical complications, and 6% of the patients were readmitted. The patients' acceptance of this concept was high. CONCLUSION: Fast-track rehabilitation resulted in a decreased rate of general complications and accelerated rehabilitation in thoracic surgery.

New insights into the pathology of Parkinson's disease: does the peripheral autonomic system become central?

Recent studies in aged, neurologically unimpaired subjects have pointed to a specific induction site of the pathological process of Parkinson's disease (PD) in the region of the dorsal glossopharyngeus-vagus complex as well as in the anterior olfactory nucleus. From the lower brainstem, the disease process would then pursue an ascending course and involve more rostral brainstem areas, limbic structures, and eventually the cerebral cortex. One barrier to the acceptance of the caudal medullary structures as the induction site of PD pathology is that not all parts of the nervous system have been investigated for the presence of PD-associated lesions in cases of early asymptomatic PD. Using alpha-synuclein immunostaining, we investigated the brain, the sacral, and thoracic autonomic nuclei of the spinal cord as well as several components of the peripheral autonomic nervous system in a autopsy cohort of 98 neurologically unimpaired subjects aged 64 or more. Our data indicate that the autonomic nuclei of the spinal cord and the peripheral autonomic nervous system belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves in neurologically unimpaired older individuals, thus providing a pathological basis for early premotor autonomic dysfunctions at a prodromal stage of PD.

Endocrine alterations associated with extended time interval between estrus and ovulation in high-yield dairy cows.

Short fertile half-lives of the male and female gametes in the female tract necessitate accurate timing of artificial insemination. We examined the possible association between extension of the estrus to ovulation (E-O) interval and alterations in concentrations of estradiol, progesterone, and the preovulatory LH surge before estrus and ovulation. High-yielding Holstein cows (n = 74 from a total of 106) were synchronized and were examined around the time of the subsequent estrus. They were observed continuously for estrual behavior. Blood samples were collected before and after estrus, and ultrasound checks for ovulation were made every 4 h. About three-quarters of the cows exhibited short (but normal) E-O intervals of 22 to 25 h (25%) or normal intervals of 25 to 30 h (47%); 17% of them displayed a long (but normal) E-O interval of 31 to 35 h, and about 10% exhibited a very long E-O interval of 35 to 50 h. Extended E-O interval comprised estrus-to-LH surge and LH surge-to-ovulation intervals that were both longer than normal. Pronounced changes in hormonal concentrations were noted before ovulation in the very long E-O interval group of cows: progesterone and estradiol concentrations were reduced, and the preovulatory LH peak surge was markedly less than in the other 3 groups. Postovulation progesterone concentrations during the midluteal phase were lesser in the very long and the long E-O interval groups compared with those in the short and normal interval groups. Season, parity, milk yield, and body condition did not affect the estrus to LH surge, LH surge to ovulation, and E-O intervals. The results indicate an association between preovulatory-reduced estradiol concentrations and a small preovulatory LH surge, on the one hand, and an extended E-O interval, on the other hand. Delayed ovulation could cause nonoptimal timing of AI, a less than normal preovulatory LH surge that may be associated with suboptimal maturation of the oocyte before ovulation, or reduced progesterone concentrations before and after ovulation. All may be factors associated with poor fertility in cows with a very long E-O interval.

Alpha-synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects.

Studies on cases with incidental Lewy body disease (ILBD) suggest that alpha-synuclein (alphaSN) pathology of Parkinson's disease (PD) starts in lower brainstem nuclei and in the olfactory bulb. However, medullary structures as the induction site of alphaSN pathology have been questioned as large parts of the nervous system, including the spinal cord and the peripheral autonomic nervous system (PANS), have not been examined in ILBD. Thus, the time course of PD lesions in the spinal cord or PANS in relation to medullary lesions remains unknown. We collected 98 post mortem cases with no reference to PD-associated symptoms on clinical records. alphaSN pathology was found in the central nervous system, including the spinal cord, and in the PANS in 17 (17.3%) cases. alphaSN pathology was encountered in autonomic nuclei of the thoracic spinal cord, brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in 15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in 14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral horns, a high number of alphaSN lesions was also found in non-autonomic spinal cord nuclei. Considering supraspinal structures our cases corresponded roughly to the recently described sequential order of alphaSN involvement in PD. Our study indicates, however, that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves. A larger cohort of ILBD cases will be needed to pinpoint the precise induction site of alphaSN pathology among these structures.

[The role of anesthesiology in fast track concepts in colonic surgery]. / Die Aufgabe der Anästhesiologie bei der Umsetzung operativer "Fast track-Konzepte". Darstellung am Beispiel der Fast-track-Kolonchirurgie.

In the present study the "fast-track rehabilitation" protocol of the Charité university hospital for patients undergoing elective colonic resection is described. The underlying principles, clinical pathways and outcome data from 208 patients are shown. Particularly anesthesiological aspects of this multimodal approach, such as modified preoperative and postoperative fluid management, changed guidelines for preoperative fasting, effective analgetic therapy using epidural analgesia and avoiding high systemic doses of opioids, use of short-acting anesthetic agents, and maintenance of normothermia as well as normovolemia are presented and discussed. In comparison to outcome data before "fast-track rehabilitation" was established, the duration of postoperative hospital stay has been reduced from 12 to 5 days, the number of general complications (pneumonia, duodenal ulcer bleeding, urinary tract infection, cerebral, cardiac and renal dysfunction) decreased from 20% to 7%, whereas surgical complications remained constant at 17% (8% wound infections, 3% anastomotic insufficiency).

[Implementation of modern operating room management -- experiences made at an university hospital]. / Implementierung eines OP-Statuts -- Erfahrungen unter den Bedingungen einer Universitätsklinik.

Caused by structural changes in health care the general need for cost control is evident for all hospitals. As operating room is one of the most cost-intensive sectors in a hospital, optimisation of workflow processes in this area is of particular interest for health care providers. While modern operating room management is established in several clinics yet, others are less prepared for economic challenges. Therefore, the operating room statute of the Charité university hospital useful for other hospitals to develop an own concept is presented. In addition, experiences made with implementation of new management structures are described and results obtained over the last 5 years are reported. Whereas the total number of operation procedures increased by 15 %, the operating room utilization increased more markedly in terms of time and cases. Summarizing the results, central operating room management has been proved to be an effective tool to increase the efficiency of workflow processes in the operating room.

Control of trapped-ion quantum states with optical pulses.

We present new results on the quantum control of systems with infinitely large Hilbert spaces. A control-theoretic analysis of the control of trapped-ion quantum states via optical pulses is performed. We demonstrate how resonant bichromatic fields can be applied in two contrasting ways--one that makes the system completely uncontrollable and the other that makes the system controllable. In some interesting cases, the Hilbert space of the qubit-harmonic oscillator can be made finite, and the Schrödinger equation controllable via bichromatic resonant pulses. Extending this analysis to the quantum states of two ions, a new scheme for producing entangled qubits is discovered.

Effects of GnRH administered to cows at the onset of estrus on timing of ovulation, endocrine responses, and conception.

Two experiments examined effects of GnRH administered within 3 h after onset of estrus (OE) on ovulation and conception in dairy cows. In experiment 1, 46 cows received either saline, 250 microg of GnRH, or 10 microg of the GnRH analogue, Buserelin. Cows were observed for estrus, blood samples were collected, and ovulations were monitored by ultrasound. In controls, 76% of cows had intervals from estrus to ovulation of < or = 30 h and 24% had intervals > 30 h. Treatment with either GnRH or GnRH analogue (data combined) increased magnitude of LH surges and decreased intervals from estrus to LH surge or to ovulation. Treated cows all ovulated < or = 30 h after OE. Among control cows, plasma estradiol concentrations before estrus correlated positively with amplitudes of LH surges. Higher plasma progesterone was observed in the subsequent estrous cycle in GnRH-treated cows compared to control cows with delayed ovulations. Experiment 2 included 152 primiparous and 211 multiparous cows in summer and winter. Injection of GnRH analogue at OE increased conception rates (CR) from 41.3 to 55.5% across seasons. In summer, GnRH treatment increased CR from 35.1 to 51.6%. Across seasons, GnRH increased CR from 36.0 to 61.5% in cows with lower body condition at insemination and GnRH increased CR (63.2 vs. 42.2%) in primiparous cows compared to controls. Use of GnRH eliminated differences in CR for cows inseminated early or late relative to OE and increased CR in cows having postpartum reproductive disorders. In conclusion, GnRH at onset of estrus increased LH surges, prevented delayed ovulation, and may increase subsequent progesterone concentrations. Treatments with GnRH increased conception in primiparous cows, during summer, and in cows with lower body condition.