text:
Q: How to unarchive BOOL property with NSKeyedUnarchiver? I have class for playing sound in app.
I implemented on/off switch(on GUI), for disabling and enablining sound play.
I am using BOOL property for that and this is working.
Now I am trying to implement saving that BOOL (is sound on/off) in file so that next time when app is started state is automatically restored.
For that I am using NSCoding protocol, archiving is working but I have problem with unarchiving.
My app will not start it will just show black screen.
This is my code, only part that I think it is important.
GTN_Sound.h
#import <Foundation/Foundation.h>
#import <AudioToolbox/AudioToolbox.h> // for playing sound

@interface GTN_Sound : NSObject <NSCoding>

@property(nonatomic, readwrite, unsafe_unretained) BOOL isSoundOn;

+ (id)sharedManager;
- (void)playWinSound;
- (void)playLoseSound;

@end

GTN_Sound.m
#pragma mark - NSCoding Methods

- (void)encodeWithCoder:(NSCoder *)aCoder
{
    [aCoder encodeBool:self.isSoundOn forKey:@"isSoundOn"];
}

- (instancetype)initWithCoder:(NSCoder *)aDecoder
{
    self = [GTN_Sound sharedManager];

    if (self) {
        _isSoundOn = [aDecoder decodeBoolForKey:@"isSoundOn"];
    }

    return self;

}

I think that code is so far so good ?
Continuation of GTN_Sound.m
#pragma mark - itemArchivePath Method

- (NSString *)itemArchivePath
{
    // Make sure that the first argument is NSDocumentDirectory
    // and not NSDocumentationDirectory
    NSArray *documentDirectories =
    NSSearchPathForDirectoriesInDomains(NSDocumentDirectory,
                                        NSUserDomainMask, YES);
    // Get the one document directory from that list
    NSString *documentDirectory = [documentDirectories firstObject];

    return [documentDirectory stringByAppendingPathComponent:@"sound.archive"];
}

#pragma mark - custom seter Method

- (void)setIsSoundOn:(BOOL)theBoolean {

    NSLog(@"My custom setter\n");
    if(_isSoundOn != theBoolean){
       _isSoundOn = theBoolean;

       NSString *path = [self itemArchivePath];

       [NSKeyedArchiver archiveRootObject:self toFile:path]; // this is doing save
}

}
It is done that for every time when switch on GUI is changed I do the savings.
This look fine from my side, because I am not expecting that user will change this many times.
Now the unarchiving comes and I thin that here are some problems.
#pragma mark - Singleton Methods

+ (id)sharedManager {
    static GTN_Sound *sharedMyManager = nil;

    // to be thread safe
    static dispatch_once_t onceToken;
    dispatch_once(&onceToken, ^{
        sharedMyManager = [[self alloc] initPrivate];
    });

    return sharedMyManager;
}

- (instancetype)init
{
    @throw [NSException exceptionWithName:@"Singleton"
                                   reason:@"Use +[GTN_Sound sharedManager]"
                                 userInfo:nil];
    return nil;
}

// Here is the real (secret) initializer
- (instancetype)initPrivate
{
    self = [super init];

    if (self) {
        NSString *path = [self itemArchivePath]; // do as iVar, for futture
        self = [NSKeyedUnarchiver unarchiveObjectWithFile:path];
        //_isSoundOn = [NSKeyedUnarchiver unarchiveObjectWithFile:path];

    }

    return self;
}

I think that problem is in this line
self = [NSKeyedUnarchiver unarchiveObjectWithFile:path];

But have no idea how to fix it.
I have read that when I am doing archiving, that I need to archive all properties of object.
Does this apply to private ivars also ?
Any help is appreciated.
Thanks

A: You can only archive NSObject inheriting objects. ie. NSNumber
[NSKeyedArchiver archiveRootObject:@YES toFile:path]; //to save
_isSoundOn = [[NSKeyedUnarchiver unarchiveObjectWithFile:path] boolValue]; //to load


text:
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text:
Q: Error when trying to run a program that creates a Java DataBase. What am I missing? This is a sample program from my book, I need to run this before I run my own assignment program to access the database and retrieve data. My problem is, this code doesn't run normally, it gives me:
"ERROR: No suitable driver found for jdbc:derby:CityDB;create=true"

at runtime.

I am using IntelliJ 13 - Community Edition.
import java.sql.*;

/**
This program creates the CityDB database.                                    *
*/

public class CreateCityDB {

public static void main(String[] args) throws Exception {
    String sql;
    final String DB_URL = "jdbc:derby:CityDB;create=true";

    try {
        // Create a connection to the database.
        Connection conn = DriverManager.getConnection(DB_URL);

        // Create a Statement object.
        Statement stmt = conn.createStatement();

        // Create the Dvd table.
        System.out.println("Creating the City table...");
        stmt.execute("CREATE TABLE City ("    +
                    "CityName CHAR(25) NOT NULL PRIMARY KEY, "   +
                    "Population DOUBLE)");

        // Add some rows to the new table.
        sql = "INSERT INTO City VALUES" +
                "('Beijing', 12500000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Buenos Aires', 13170000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Cairo', 14450000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Calcutta', 15100000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Delhi', 18680000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Jakarta', 18900000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Karachi', 11800000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Lagos', 13488000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('London', 12875000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Los Angeles', 15250000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Manila', 16300000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Mexico City', 20450000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Moscow', 15000000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Mumbai', 19200000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('New York City', 19750000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Osaka', 17350000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Sao Paulo', 18850000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Seoul', 20550000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Shanghai', 16650000)";
        stmt.executeUpdate(sql);

        sql = "INSERT INTO City VALUES" +
        "('Tokyo', 32450000)";
        stmt.executeUpdate(sql);

        // Close Resources
        stmt.close();
        conn.close();
        System.out.println("Done");
    }
    catch(Exception ex) {
        System.out.println("ERROR: " + ex.getMessage());
    }

}

}

A: No suitable driver means you are not adding the required jar in your class path.
If you are using eclipse then follow this

*

*right click on project

*click build path->configure build path

*then click libraries tab

*Then click add external jar and give the path of the jar file.

*Re run the project

Follow the steps for IntelliJ IDEA

*

*Click File

*Click Project Structure(short cut ctrl + shift + alt + s)

*Then click module then on dependencies

*Then click on  add->project library

A: Load the class first using:
Class.forName("org.apache.derby.jdbc.EmbeddedDriver");

Edit:
Turns out JavaDB is not readily available in the JDK. See http://db.apache.org/derby/integrate/plugin_help/derby_app.html#Changing+the+application+to+use+the+Derby+Embedded+Driver.

To use Derby in its embedded mode set your CLASSPATH to include the jar files listed below:
  derby.jar: contains the Derby engine and the Derby Embedded JDBC driver

Edit 2:
I've tried compiling your example with only derby.jar on the classpath and it fails. After adding derbyclient.jar too it works (from JDK7).

redpajama_set_name: RedPajamaStackExchange


text:
Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR)
Ayako Fuchigami1 na1,
Fumika Shigiyama1 na1,
Toru Kitazawa2,
Yosuke Okada3,
Takamasa Ichijo4,
Mariko Higa4,
Toru Hiyoshi5,
Ikuo Inoue6,
Kaoru Iso7,
Hidenori Yoshii8,
Takahisa Hirose1 &
Naoki Kumashiro ORCID: orcid.org/0000-0002-5432-35991
Cardiovascular Diabetology volume 19, Article number: 1 (2020) Cite this article
Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight.
This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring.
Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m2; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability.
Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes.
Trial registration Trial number, UMIN000028014; registered on June 30, 2017
Approximately 415 million people worldwide are currently living with diabetes, and the prevalence of type 2 diabetes is increasing [1]. Type 2 diabetes is associated with micro- and macrovascular complications leading to cardiovascular diseases [2, 3], which increase the mortality in this population [3]. Thus, the management of patients with type 2 diabetes should focus not only on lowering blood glucose levels but also on preventing vascular complications.
Among the various medications available for type 2 diabetes, oral glucose-lowering agents such as dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors have recently become the focus of substantial research. Some SGLT2 inhibitors improved cardiovascular outcomes in patients with type 2 diabetes [4, 5]. The Dapagliflozin Effect on CardiovascuLAR Events [DECLARE-TIMI 58] trial showed the favorable effect of dapagliflozin, one of the SGLT2 inhibitors, compared to the effects of placebo on suppression of hospitalization for heart failure with neutral effect on the following major adverse cardiovascular events: cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke (MACE) [6]. On the other hand, the results of placebo-controlled non-inferiority randomized clinical trials suggested that DPP-4 inhibitors have a neutral effect of cardiovascular events in patients with type 2 diabetes [7,8,9].
Some studies have compared SGLT2 inhibitors and DPP-4 inhibitors regarding their glucose-lowering effect [10,11,12,13,14], and recent comparative studies with retrospective observational design indicated that SGLT2 inhibitors were superior to DPP-4 inhibitors for preventing cardiovascular events [15, 16]. However, there is limited evidence with prospective studies on the effect of SGLT2 inhibitors versus DPP-4 inhibitors on cardiovascular risk. Strategies for the prevention of cardiovascular events in type 2 diabetes include not only improvement of HbA1c level but also avoidance of hypoglycemia [17, 18] and maintenance of optimal body weight [19]. The scope of such strategies should be considered when assessing the efficacy of SGLT2 inhibitors and DPP-4 inhibitors for glycemic control. In addition, patients included in the previous randomized controlled trial using SGLT2 inhibitors and DPP-4 inhibitors had high prevalence of cardiovascular disease with long duration of type 2 diabetes [6, 9]. Thus, the effect of such drugs on specific cardiovascular risk factors in Japanese patients with early-stage type 2 diabetes has not been clarified.
In the present study, we aimed to clarify the efficacy of dapagliflozin versus sitagliptin for improving cardiometabolic risk factors including high glycated hemoglobin (HbA1c) level, hypoglycemia, and body weight in Japanese patients with type 2 diabetes. Specifically, we assessed the success of maintaining HbA1c levels < 7.0% (53 mmol/mol) while avoiding hypoglycemia and achieving adequate body weight reduction. This prospective trial was the first study to clinically evaluate the therapeutic benefits of dapagliflozin and sitagliptin on cardiometabolic risks by focusing concomitantly on achieving target HbA1c level < 7.0% (53 mmol/mol), maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL (avoidance of hypoglycemia), and ≥ 3.0% loss of body weight in patients with type 2 diabetes [20]. Notably, hypoglycemia was carefully monitored using a flash glucose monitoring (FGM) system [21]. Thus, the results of the present study may help clarify the optimal choice of oral glucose-lowering agents and establish an effective treatment strategy for preventing cardiovascular events in early-stage type 2 diabetes.
The DIVERSITY-CVR study is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative study, of which the design and rationale have been reported previously [20], registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000028014). The study protocol was approved by the ethics committee of Toho University Omori Medical Center and by the ethics review boards of all participating institutions. Written informed consent was obtained from all participants. To minimize bias, participant randomization and data collection, management, and analysis were conducted by third-party entity (Soiken Inc., Tokyo, Japan).
The study enrolled 340 outpatients with type 2 diabetes managed at any of the 51 participating clinics in Japan. The full list of study investigators is provided in Additional file 1. Enrollment began in July 2017 and ended in June 2018. The inclusion criteria were as follows: (1) patients with type 2 diabetes who had not used any glucose-lowering agents within 8 weeks before consenting, or those who had used only metformin; (2) those with HbA1c (NGSP values) levels of ≥ 7.1% (54 mmol/mol) but not > 10.0% (86 mmol/mol); (3) those aged between 20 and 80 years; (4) those with body mass index (BMI) of ≥ 23 kg/m2; (5) those who could be monitored closely for medication compliance; and (6) those who provided written consent to participate in the study. The following exclusion criteria were used: (1) patients with type 1 diabetes or secondary diabetes; (2) those with a medical history of diabetic ketoacidosis; (3) those with a medical history of myocardial infarction, cerebral infarction, or stroke within 12 weeks before consenting to the study; (4) those with severe liver disease having more than fivefold higher than normal levels of AST and ALT; (5) those with renal disease [serum creatinine ≥ 1.3 mg/dL, or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2]; (6) those with unstable hypertension or dyslipidemia within 12 weeks before consent to the study; (7) those who were pregnant or breastfeeding or were planning to become pregnant during the study; and (8) dehydrated patients [test results showed abnormalities in hematocrit or blood urea nitrogen (BUN) or patient complaints of dehydration].
Randomization and study intervention
After obtaining informed consent, eligible subjects were randomly assigned in a 1:1 ratio to receive dapagliflozin (5.0–10 mg/day) or sitagliptin (50–100 mg/day) add-on therapy. The randomization sequence was generated using a computer-based dynamic allocation method aiming to balance key baseline characteristics (HbA1c level, BMI, and metformin dose at the time of provision of consent). After enrollment, all concomitant prescriptions were fixed. Patients who required a change in the dose of concomitant drugs or the use of additional medications such as other glucose-lowering, antihypertensive, lipid-lowering, or antiplatelet agents were excluded from the study. Baseline measurements of blood samples and FGM measurements for > 5 days were performed during the 8-week screening period. The treatment drug (dapagliflozin 5.0 mg/day or sitagliptin 50 mg/day) was administered for 24 weeks. The dose could be increased after the first 8 weeks (dapagliflozin to 10 mg/day and sitagliptin to 100 mg/day) if necessary, to achieve the target HbA1c level of < 7.0% (53 mmol/mol). The intervention start date was set as the study start date, and the assigned treatment was continued for 24 weeks.
Study outcomes
The primary endpoint was the proportion of patients who achieved the composite endpoint of three indices from baseline to week 24: maintenance of HbA1c level ≤ 7.0% (53 mmol/mol); maintenance of sensor glucose > 3.0 mmol/L or > 54 mg/dL (avoidance of hypoglycemia); and body weight loss ≥ 3.0% relative to baseline. We chose this composite endpoint in order to minimize the bias associated with competing risk factors [22].
In addition to the individual components of the composite endpoint, secondary endpoints included the changes (relative to baseline) in the following indices: body weight and BMI; metabolic indices including systolic blood pressure, diastolic blood pressure, fasting plasma glucose, plasma insulin, and HbA1c level; lipid indices including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; levels of serum uric acid (UA), BUN, serum creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT); eGFR; blood cell counts; and glucose variability indices measured using FGM. Medication adherence rate was also reported.
FGM measurements were used to estimate the number, duration, and area under the curve (AUC) of hypoglycemia episodes, defined as periods with sensor glucose ≤ 3.9 mmol/L (≤ 70 mg/dL) or < 3.0 mmol/L (< 54 mg/dL) within 24 h and from 23:00 to 06:00. The duration of hyperglycemia episodes (glucose > 10.0 mmol/L or > 180 mg/dL) was also assessed. Furthermore, the standard deviation (SD), coefficient of variation (CV), mean amplitude of glycemic excursion (MAGE), and continuous overall net glycemic action (CONGA) calculated every 2 and 6 h were evaluated. MAGE means the mean of the difference between consecutive glycemic peak and nadirs and CONGA means the SD of the glycemic differences recorded between the specific points on the FGM profile.
Data collection schedule
Clinical and biochemical data were collected after overnight fasting at baseline and after the 24-week treatment period. Body weight was measured at the hospital or clinic, with the subjects wearing the same type of disposable examination gowns. To check for hypoglycemia, all subjects wore the Freestyle Libre Pro® monitor (Abbott Diabetes Care, Tokyo, Japan) on the upper arm for 14 days during baseline screening and at week 24. At the end of the 14-day measurement period, the subjects removed the sensor by themselves and sent it to the third-party data management center, which was blinded to clinical information. The data management center downloaded the glucose data from the sensor and used dedicated software for analysis (Abbott Diabetes Care). FGM data corresponding to the first 24 h recorded were omitted from the analysis, which included data collected during the subsequent 5 days. To estimate medication adherence rates, all subjects were requested to record their daily intake of medication using a medication diary.
During the course of the study, the patients were monitored for adverse events (AEs) through regular medical checkups. When an AE occurred, with or without any relationship with the study drug, the investigator reported the details immediately to the participating institution, principal investigator, and study administration office. All AEs, including drug-related side effects and abnormal clinical test results, were diligently reported and documented.
Sample size calculation and statistical analysis
We used data from our previous studies [23, 24] to estimate the expected difference in the primary endpoint and determine the required sample size for this study [20]. The details of determining the sample size are described in the previous rationale report of this study [20]. Analyses for the primary and secondary endpoints were primarily performed on the full analysis set (FAS), which included all subjects assigned to a study intervention. However, subjects without data for the primary endpoint or with a significant study protocol violation were excluded from the FAS. The details of observed severe protocol violations in this study were as follows; (1) sulfonylurea was started at the same time as the dapagliflozin was administered, (2) ipragliflozin was administered, (3) insulin therapy was administered, (4) sitagliptin 25 mg was administered. Safety analysis (AE incidence) included all treated patients. Summary statistics were calculated for continuous variables. The t-test and Fisher's exact test were used to assess differences in baseline characteristics between the groups. For the primary endpoint (proportion of participants who achieved the composite endpoint), between-group comparison was performed using the chi-square test. Additionally, for sensitivity analysis, the Mantel–Haenszel test was performed after adjusting for allocation factors (HbA1c level < 8.5%/≥ 8.5%, BMI < 27 kg/m2/≥ 27 kg/m2, metformin dose ≤ 500 mg/> 500 mg) to estimate the risk difference and its 95% confidence interval. For the secondary endpoints (change in various indices from baseline to week 24), the two-sample t-test and analysis of covariance were used; the results were expressed as adjusted mean (standard error). Analysis of covariance included HbA1c level, BMI, and dose of metformin as covariates (as described above), as well as the baseline value of each analyzed variable. For variables with non-normal distribution, data were logarithmically transformed. FGM data including the number, duration, and AUC of hypoglycemia episodes were compared between the groups using the Wilcoxon rank sum test. All statistical analyses were performed by independent staff at the administrative office of the DIVERSITY-CVR study (Soiken Inc., Tokyo, Japan), using SAS version 9.4 (SAS Institute, Cary, NC).
Human rights and ethical principles
All investigators involved in this study complied with the World Medical Association Declaration of Helsinki (2013 revision) and Ethical Guidelines for Medical and Health Research Involving Human Subjects (December 22, 2014, Ministry of Education, Culture, Sports, Science and Technology/Ministry of Health, Labor and Welfare), as well as with other relevant bylaws and regulations.
In this study, 2568 subjects were screened and 2228 patients were ineligible (143 subjects denied consent, 1892 due to screening failure, 81 due to personal reasons, and 112 for other reasons). Three hundred forty patients were enrolled and randomized, and 331 completed the study and were included in the FAS (168 and 163 patients in the dapagliflozin and sitagliptin groups, respectively, Fig. 1). The baseline clinical characteristics are summarized in Table 1. Most patients were middle aged (average age, approximately 58 years) and overweight (average BMI, approximately 28 kg/m2). Disease duration was relatively short (on average, approximately 6 years), with moderate hyperglycemia (average HbA1c level, 7.8% or 62 mmol/mol). The prevalence of macrovascular complications was low (< 5.0%). Approximately 40% of patients were drug-naïve, and the average dose of biguanides was low (approximately 550 mg upon setting the dose of drug-naïve patients to 0 mg). The groups did not differ regarding any baseline clinical characteristics other than the prevalence of diabetic nephropathy, which was significantly lower in the dapagliflozin group than in the sitagliptin group (15 vs. 33, P < 0.05), although this difference was not reflected in the baseline eGFR (79.0 ± 18.5 vs. 78.9 ± 16.9 mL/min/1.73 m2). There was no between-group difference in medication adherence (97.0% vs. 97.5%).
Flow chart of participant enrollment, allocation, and analysis. FAS full analysis set
Table 1 Baseline characteristics
Superiority of dapagliflozin regarding the primary endpoint
The proportion of patients who achieved the composite endpoint of HbA1c level maintenance ≤ 7.0% (53 mmol/mol), avoidance of hypoglycemia, and body weight loss ≥ 3.0% after 24 weeks of treatment is summarized in Table 2. We conducted analyses using the chi-square test and Mantel–Haenszel test (see also Additional file 2: Table S1). The primary endpoint (proportion of patients who achieved the composite endpoint of glucose control, hypoglycemia avoidance, and adequate body weight loss) was significantly higher in the dapagliflozin group than in the sitagliptin group (Table 2). The success of glycemic control (maintenance of HbA1c level ≤ 7.0% or 53 mmol/mol) was comparable between the groups (Table 2). Hypoglycemia (glucose < 3.0 mmol/L or < 54 mg/dL) was avoided in the majority of patients in both groups (Table 2). On the other hand, the proportion of patients who achieved ≥ 3.0% loss in body weight was significantly higher in the dapagliflozin group than in the sitagliptin group (Table 2).
Table 2 Achieved number or ratio regarding improvement of cardiometabolic risks in patients with early-stage type 2 diabetes
Effects on other cardiometabolic risk factors
Other cardiometabolic risk factors were also evaluated as secondary endpoints (Tables 3, Additional file 3: Table S2 and Additional file 4: Table S3). Although no significant differences between the groups were found regarding the change in HbA1c level, the improvement in fasting plasma glucose was significantly more pronounced in the dapagliflozin group than in the sitagliptin group: − 23.0 (2.6) vs. − 15.1 (2.6) mg/dL (P < 0.01; Table 3). The improvement in fasting plasma insulin was also significantly more pronounced in the dapagliflozin group than in the sitagliptin group: − 0.17 (0.06) vs. 0.17 (0.06) ln(μU/mL) (P < 0.001; Table 3). Regarding lipid parameters, HDL cholesterol experienced a significantly more pronounced increase in the dapagliflozin group than in the sitagliptin group: 0.07 (0.01) vs. 0.00 (0.01) mg/dL (P < 0.001; Table 3). However, the changes in triglyceride and LDL cholesterol were comparable between the groups. The dapagliflozin group experienced significantly more pronounced decrease in AST and ALT, increase in hematocrit, decrease in UA, and increase in BUN as well as significantly less pronounced increase in serum creatinine and decrease in eGFR (Table 3). The number, duration, and AUC of hypoglycemic episodes within 24 h and from 23:00 to 06:00 were comparable between the groups (Additional file 3: Table S2). The duration of hyperglycemia episodes was also comparable between the groups (Table 3). However, FGM data reflecting glucose variability, including SD, CV, MAGE, and CONGA (at 2 and 6 h), showed significantly larger improvement in the sitagliptin group than in the dapagliflozin group (Table 3).
Table 3 Summary of secondary endpoints
Safety outcomes
During the study, 41 of 168 patients (24.3%) in the dapagliflozin group and 41 of 163 patients (24.7%) in the sitagliptin group reported AEs (Additional file 5: Table S4). No significant differences in AEs were found between the groups. No serious AEs including severe hypoglycemia or hyperglycemia were observed in either group.
This prospective randomized study enrolled 340 patients with early-stage type 2 diabetes (duration of diabetes: around 6 years). On average, the participants were overweight (BMI, approximately 28 kg/m2) and had inadequate glycemic control (HbA1c level, 7.8% or 62 mmol/mol) with metformin only or without glucose-lowering agents. The results of this study suggest that dapagliflozin is superior to sitagliptin for improving cardiometabolic risk factors in overweight Japanese patients with early-stage but inadequately controlled type 2 diabetes.
In this study, glycemic control (HbA1c level < 7.0% or 53 mmol/mol) was achieved in around 50% in both groups. Although it was reported that each 1.0% reduction in HbA1c level was significantly associated with a 14% and 12% reduction in the risk of myocardial infarction and stroke, respectively [25], intensive glycemic control can lead to more hypoglycemic episodes and does not always reduce the incidence of cardiovascular events or mortality [26]. In fact, hypoglycemia is recognized as a potent marker of high risk for cardiovascular events and mortality [18]. In the present study, we found that hypoglycemia assessed using FGM was successfully avoided in approximately 90% of participants in both groups. No significant difference was observed regarding hypoglycemia between the groups. These data indicate that both dapagliflozin and sitagliptin can be used to improve glycemic control while minimizing hypoglycemic episodes within 24 weeks of treatment in Japanese patients with type 2 diabetes.
On the other hand, ≥ 3.0% loss in body weight over the course of 24 weeks was achieved significantly more often in the dapagliflozin group (54.4% of the allocated patients). The change in body weight at 24 weeks was − 2.7 ± 3.0 kg in the dapagliflozin group and − 0.4 ± 2.6 kg in the sitagliptin group. The previous studies indicated that the change in body weight was approximately − 3.0 kg with 10 mg of dapagliflozin treatment for 24-week [6], and − 0.2 ± 0.2 kg with 100 mg of sitagliptin treatment [27]. Thus, the changes in body weight seen in this study were similar to those observed in other previous reports. Obesity is considered a major risk factor of cardiovascular disease [19]. Recently, Rosenzweig et al. reported that body weight loss of > 5.0% per year protects against cardiovascular disease in overweight individuals [28]. In overweight or obese Japanese populations, the minimum weight reduction required to improve obesity-related risk factors or conditions was reported at 3.0% [29], which was the threshold used in our present study. Recently, Reaven et al. reported significant reduction in cardiovascular risk using SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists [4, 30], concluding that approaches beyond glycemic control (such as body weight reduction) represent important strategies for reducing the risk of cardiovascular events and death among populations with type 2 diabetes [31].
Although the achievement ratio of the primary composite endpoints may be regarded as low in both groups, it resulted from the multiplication of each achievement ratio of the individual components of the composite endpoint. Previous report suggested that composite endpoints were preferred to assess the clinical benefit of intervention avoiding misinterpretation associated with competing risks factor bias and challenge of using a single outcome to validate the study objective in trials on patients with diabetes [22]. Regarding the composite endpoint of cardiometabolic risk factors, our study showed the superiority of dapagliflozin compared to that of sitagliptin. It seems that the superiority of dapagliflozin stemmed mainly from the effect on body weight reduction.
In our study, dapagliflozin was more effective than sitagliptin not only regarding body weight reduction but also regarding the decrease in AST, ALT, fasting plasma glucose level, and fasting plasma insulin level. These results are consistent with those of previous reports that SGLT2 inhibitors ameliorate hepatic steatosis [32] and improve insulin sensitivity [33]. Both hepatic steatosis [34] and insulin resistance [35] are known risk factors of cardiovascular disease. Taken together, these data suggest that dapagliflozin might indeed be superior to sitagliptin for the cardiometabolic effects. In addition, previous studies reported the preferable cardiometabolic effects regarding SGLT2 inhibitors [36,37,38,39]. Dapagliflozin also showed stronger therapeutic effects on other indices that might contribute to the prevention of cardiovascular events. For example, the increase in HDL cholesterol was significantly more pronounced in the dapagliflozin group than in the sitagliptin group. Previous studies reported that an increase in HDL cholesterol concentration is associated with a decrease in the risk of coronary artery disease [40]. The increase in hematocrit count was also significantly more pronounced in the dapagliflozin group. Ferrannini et al. indicated that SGLT2 inhibitors may increase hematocrit count by stimulating erythropoiesis, which increases oxygen transport to the tissues and protects from cardiovascular events [41]. Hyperuricemia is also known as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes populations [42]. Our present finding that the decrease in UA was significantly more pronounced in the dapagliflozin group also supports the choice of dapagliflozin over sitagliptin. Recent evidence from placebo-controlled trials suggests that SGLT2 inhibitors suppress the progression of kidney disease [43] and lower the risk of kidney failure [44]. In the present study, the decrease in kidney function (assessed in terms of serum creatinine and eGFR) was significantly smaller in the dapagliflozin group than in the sitagliptin group. A previous study reported that an eGFR yearly decline of > 1.63 mL/min/1.73 m2 is associated with a significant increase in the incidence of major cardiovascular events [45]. These data also support the choice of dapagliflozin over sitagliptin to promote renal and cardiovascular protection in patients with early-stage type 2 diabetes.
Our present study was the first to compare the efficacy of dapagliflozin and sitagliptin in terms of glucose fluctuation evaluated using the Freestyle Libre Pro® device. Interestingly, we found that sitagliptin was superior to dapagliflozin regarding glucose variability (SD, CV, MAGE, and CONGA at 2 and 6 h) assessed using FGM. Nevertheless, the change in HbA1c level was comparable between the groups and dapagliflozin provided a larger reduction in fasting plasma glucose. Taken together, these findings suggest that sitagliptin might predominantly lower postprandial blood glucose and suppress glucose fluctuation. As increased glucose variability was reportedly associated with increased risk of cardiovascular events [46, 47], sitagliptin might also contribute to the prevention of cardiovascular events through suppression of glucose variability, at least partly.
Several limitations of the study should be mentioned. First, this was an open-label study and all patients were Japanese. The Trial Evaluating Cardiovascular Outcomes with Sitagliptin reported that East Asians had the greatest HbA1c level response to sitagliptin [48]. Furthermore, the glycemic response to DPP-4 inhibitors is larger in Asian subjects than in other races [49]. Therefore, our findings that HbA1c level reduction was comparable between the groups and that the improvement in glucose variability was better for sitagliptin may not apply fully to Caucasians. Future trials with larger sample size, adequate ethnicity representation, and long-term observation are necessary to confirm the generalizability of our results. Second, the baseline prevalence of diabetic nephropathy was higher in the sitagliptin group than in the dapagliflozin group. As urine albumin level was not measured in this study, we could not evaluate the change in urine albumin levels. However, baseline eGFR was similarly well preserved in both groups (at approximately 79.0 mL/min/1.73 m2). Third, although we recorded AEs during the study period of 24 weeks, we did not measure surrogate markers of cardiac function or record the actual incidence of cardiovascular events. Such measurements would provide a better understanding of the preventive effects of the intervention drugs on arteriosclerosis and cardiovascular disease.
To our knowledge, the DIVERSITY-CVR study was the first study to directly compare the cardiometabolic risk reduction between dapagliflozin and sitagliptin as first- or second-line therapies in Japanese patients with early-stage type 2 diabetes. Although dapagliflozin and sitagliptin provided similar effects on glycemic control with avoidance of hypoglycemic episodes, adequate loss in body weight occurred significantly more frequently in the dapagliflozin group. Additionally, various cardiometabolic indices improved to a significantly greater extent in the dapagliflozin group than in the sitagliptin group. Taken together, these data suggest that dapagliflozin therapy may be more effective for primary prevention of cardiometabolic risk factors in overweight patients with early-stage type 2 diabetes. Our findings are potentially useful in establishing an effective treatment strategy for patients with early-stage type 2 diabetes.
The datasets were analyzed during the current study are available from the corresponding author on reasonable request.
AEs:
alanine aminotransferase
AST:
aspartate aminotransferase
AUC:
area under the curve
BUN:
CONGA:
continuous overall net glycemic action
DPP-4:
dipeptidyl peptidase 4
estimated glomerular filtration rate
FAS:
full analysis set
FGM:
flash glucose monitoring
HbA1c:
high glycated hemoglobin
HDL:
high-density lipoprotein
LDL:
low-density lipoprotein cholesterol
mean amplitude of glycemic excursion
SD:
SGLT2:
sodium-glucose cotransporter-2
UA:
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Schork A, Saynisch J, Vosseler A, Jaghutriz BA, Heyne N, Peter A, et al. Effect of SGLT2 inhibitors on body composition, fluid status and renin-angiotensin-aldosterone system in type 2 diabetes: a prospective study using bioimpedance spectroscopy. Cardiovasc Diabetol. 2019;18:46.
Irace C, Casciaro F, Scavelli FB, Oliverio R, Cutruzzola A, Cortese C, et al. Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy. Cardiovasc Diabetol. 2018;17:52.
Handelsman Y, Mathieu C, Del Prato S, Johnsson E, Kurlyandskaya R, Iqbal N, et al. Sustained 52-week efficacy and safety of triple therapy with dapagliflozin plus saxagliptin versus dual therapy with sitagliptin added to metformin in patients with uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018;21:883–92.
Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8–15.
Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a "Thrifty Substrate" hypothesis. Diabetes Care. 2016;39:1108–14.
Odden MC, Amadu AR, Smit E, Lo L, Peralta CA. Uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 1999–2002. Am J Kidney Dis. 2014;64:550–7.
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295–306.
Oshima M, Jun M, Ohkuma T, Toyama T, Wada T, Cooper ME, et al. The relationship between eGFR slope and subsequent risk of vascular outcomes and all-cause mortality in type 2 diabetes: the ADVANCE-ON study. Diabetologia. 2019;62:1988–97.
Hirakawa Y, Arima H, Zoungas S, Ninomiya T, Cooper M, Hamet P, et al. Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care. 2014;37:2359–65.
Gorst C, Kwok CS, Aslam S, Buchan I, Kontopantelis E, Myint PK, et al. Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis. Diabetes Care. 2015;38:2354–69.
Davis TME, Mulder H, Lokhnygina Y, Aschner P, Chuang LM, Raffo Grado CA, et al. Effect of race on the glycaemic response to sitagliptin: insights from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Obes Metab. 2018;20:1427–34.
Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia. 2013;56:696–708.
We thank all the clinical staff and study members across Japan (listed in the Supplementary data) for their participation in this study. We thank Chie Fujita, Hirokazu Yamada, and Hiroki Takayama from Soiken Inc. (Tokyo, Japan) for their excellent technical assistance. We also thank all the participants in this study. We would like to thank Editage (http://www.editage.com) for English language editing.
This study was supported by AstraZeneca Japan K.K., the manufacturer of dapagliflozin.
Ayako Fuchigami and Fumika Shigiyama contributed equally to this article
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
Ayako Fuchigami, Fumika Shigiyama, Takahisa Hirose & Naoki Kumashiro
Division of Diabetes, Endocrinology and Metabolism, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Toru Kitazawa
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Yosuke Okada
Department of Diabetes and Endocrinology, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan
Takamasa Ichijo & Mariko Higa
Division of Diabetes and Endocrinology, Japanese Red Cross Medical Center, Tokyo, Japan
Toru Hiyoshi
Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan
Ikuo Inoue
Department of Internal Medicine, Japan Community Health Care Organization Tokyo Kamata Medical Center, Tokyo, Japan
Kaoru Iso
Department of Medicine, Diabetology and Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Hidenori Yoshii
Ayako Fuchigami
Fumika Shigiyama
Takamasa Ichijo
Mariko Higa
Takahisa Hirose
Naoki Kumashiro
AF, FS, TK, YO, TI, MH, TH2, II, KI, HY, TH1, and NK recruited the participants and collected the clinical data. AF, FS, TH1, and NK managed the study and contributed to the discussion. AF, FS, and NK wrote and edited the manuscript. All authors reviewed the manuscript and approved the final manuscript. NK is the guarantor of this work and, as such, had full access to all study data and takes responsibility for the integrity of the data and the accuracy of data analysis. All authors read and approved the final manuscript.
Correspondence to Naoki Kumashiro.
The study was approved by the Medical Ethics Committee of Toho University (approval #M18229_17024) and was conducted according to the Declaration of Helsinki and 370 current legal regulations in Japan. All patients provided written informed consent before participation.
TK. received lecture fees from Ono Pharmaceutical Co., Ltd. and Sanofi K.K.; Y.O. received lecture fees from Ono Pharmaceutical Co., Ltd., MSD K.K. and AstraZeneca K.K.; I.I. received lecture fees from Sanofi K.K.; T.H1. received research funds from AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., MSD K.K., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., Bayer Yakuhin, Ltd., Soiken Inc., Kissei Pharmaceutical Co., Ltd., and Novartis Pharma K.K., and received lecture fees from Sanofi K.K., Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kissei Pharmaceutical Co., Ltd., and AstraZeneca K.K.; N.K. received lecture fees from Ono Pharmaceutical Co., Ltd., Novo Nordisk Inc., Takeda Pharmaceutical Co., Ltd., and Sanofi-Aventis Deutschland GmbH. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Principal Investigators List.
Additional file 2: Table S1.
Adjusted risk of endpoints that affect the incidence of cardiovascular events.
Hypoglycemic episodes.
Summary of evaluated indices.
Adverse events.
Fuchigami, A., Shigiyama, F., Kitazawa, T. et al. Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR). Cardiovasc Diabetol 19, 1 (2020). https://doi.org/10.1186/s12933-019-0977-z
Cardiometabolic risk factors
Dapagliflozin
Glycemic control


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redpajama_set_name: RedPajamaGithub


text:
Police detain three people from Delhi Airport…
Sundance Award-Winning Films that ought to be…
Marvel's new trailer introduces Oscar Isaac to…
China, Iran Begin Implementation of Sweeping Strategic…
State-level coordinators appointed by MEA to ensure return of stranded Indians across the world
By Editor May 6, 2020 May 6, 2020
In a move to facilitate return of hundreds of thousands of Indians stranded around the world because of the Coronavirus pandemic, the Ministry of External Affairs has appointed state-level coordinators to ensure close coordination with various ministries, state governments and the government at the centre.
A team of 17 members from the Ministry of External Affairs has been set up to undertake the coordination of repatriation of Indian nationals. This comes soon after the Union Ministry of Home Affairs announced its plans to evacuate over 14,000 people from 13 different nations, including Philippines, Singapore, Bangladesh, Qatar, UAE, UK, Saudi Arabia, Singapore, Philippines, USA, Oman, Bahrain, and Kuwait.
According to the plan shared by MEA with the Ministry of Civil Aviation (MoCA) the evacuation process will begin from May 7 and approximately 14,800 passengers will be evacuated.
FIFA to judge Sampdoria claim from sale of Bruno Fernandes
State government acquires former CM Jayalalithaa's house to convert it into memorial: Tamil Nadu
Security forces gun down three terrorists, including a top commander of Pakistan based Hizb-ul-Mujahideen
NDT Bureau June 29, 2020 June 29, 2020
Makers Of Indian '24' Series Plot A TV Show Revolution
Editor April 19, 2013
Ishant Sharma claims six as Kiwis bowled out for 192
Editor February 14, 2014


text:
LGBTI Indians still fighting for social acceptance
Rik Glauert
First same-sex couple doubles team competes at Wimbledon
Nearly 2 out of 5 LGBTI Indians believe battling for equal rights and social acceptance is the biggest issue facing the community, a YouGov survey found.
India decriminalized gay sex in September last year.
Nearly 40% of respondents said they had witnessed a change in attitudes and perceptions towards the community since the landmark Supreme Court ruling.
Nearly half (48%) said India was progressing in terms of LGBTI rights.
'Marriage and adoption is one of the challenges faced by the community, with 31% agreeing' Deepa Bhatia, general manager, YouGov India also said in a statement.
'But the need for equal rights [in all areas] and social acceptance definitely exists.'
YouGov India quizzed 300 LGBTI Indians in June 2019.
LGBTI rights in India
India's Supreme Court in September last year ruled the country's anti-gay law was unconstitutional.
Section 377 of India's colonial-era Penal Code punished gay sex with up to 10 years in prison. But, the Supreme Court said it violated rights to privacy.
Indians, therefore, celebrated the decriminalization of an estimated 4.5 million LGBTI people.
But, LGBTI activists and leaders warned it would take time for society and businesses to accept homosexuality.
India currently does not protect LGBTI people with anti-discrimination legislation.
What's more, the transgender population has slammed a government bill purported to protect their rights.
LGBTI Dating habits in India
The YouGov surgery also found 30% of LGBTI Indians are looking for love online.
Interestingly, the most active users of LGBTI dating apps were those who identify as bisexual.
A quarter of this population reported using LGBTI apps to meet people.
'Social networks and dating apps are great avenues for the LGBTQ+ community looking for love' said Bhatia.
'These platforms provide acceptance and the option of anonymity, especially for the ones who have not come out of the closet yet.'
Hundreds of trans Indians take to the polls, but turnout is still low
What might a Narendra Modi re-election mean for LGBTI Indians?
Married Indians are looking for same-sex affairs after decriminalization
Rik Glauert 04 Jul 2019
Indian Government posts, then deletes, Grindr-inspired nutrition advert
LGBTI people in Nepal demand to be counted
Why our gay Desi wedding went viral
Delhi Commission for Women slams controversial trans rights bill in India


The company is one of the world's leading manufacturers of laser projection and measurement systems in the medical and industrial sector. Since 1984, LAP GmbH Laser has developed, produced and marketed laser applications from its main site in Lüneburg, and it has become a global leader in the field of laser components and system solutions for reproducible positioning of patients in radiation oncology. LAP also sells projection and measuring systems for a variety of industrial applications, e.g. in the steel, aerospace and wind power industries. The company has sales locations in the USA, France, China and India & the ASEAN region. In 2015, capiton acquired an interest in the company in the course of a shareholder reorganisation process. capiton was able to secure the resignation of older shareholders and the inclusion of appointed managers on the Board.


text:
Explore the Quiet Elegance of The Lodge at Wakulla Springs, Florida
December 5, 2019Sara Sheehy + Save to a List
A trip back in time.
Escape the winter blues with a trip to Edward Ball Wakulla Springs State Park in Wakulla Springs, Florida. Take a dip in the crystal-clear waters of Wakulla Springs, watch for marine wildlife and birds, go hiking, and rest your head at night in the historic, 1930s era Lodge.
When the weather gets cold, the cold head south. Quiet elegance awaits at Wakulla Springs.
About The Lodge at Wakulla Springs
The Lodge at Wakulla Springs is called "North Florida's castle," and for a good reason. It was built in 1937 by financier Edward Ball, who loved the area for its pristine and serene environment. Surrounded by 6,000 acres of forest and ancient cypress swamp, the Lodge sits on the edge of beautiful Wakulla Springs.
The building itself is a sprawling Spanish-style Lodge with 27 rooms that overlook Wakulla Springs. Each room is furnished with antique or period furniture and spacious bathrooms — a luxury in historical buildings. The Lodge has a dining room that serves three meals a day and a soda fountain and gift shop.
It is also listed on the National Register of Historic Places.
Explore the Springs
The Lodge at Wakulla Springs is right in the middle of Edward Ball Wakulla Springs State Park, so exploration is just a quick walk away. The freshwater spring itself is one of the largest and deepest in the world. It is home to alligators, manatees, many species of birds, and other wildlife.
In the morning, take a riverboat cruise from the Lodge (they leave every hour from 9:00 am to 5:00 pm) for a nature tour of the springs. The on-board guide will share information about the history of the springs and help you spot wildlife. Grab some lunch at the Lodge's Soda Fountain, which serves American classics and has the longest marble soda fountain ever built.
In the afternoon, hike some of the park's nine miles of trail (the Cherokee Sink Trail leads to an 80-foot deep sinkhole lake) and then cool off with a dip in the crystal clear, always-70-degree waters of Wakulla Springs.
End your evening in the Edward Ball Dining Room, which serves a seated breakfast, lunch, and dinner every day. Why not try the southern fried chicken or one of the seasonal farm-to-table dishes?
No matter how you enjoy the Lodge at Wakulla Springs, its quiet elegance will nestle deep into your heart.
Book a stay at The Lodge at Wakulla Springs.
All photos courtesy of The Lodge at Wakulla Springs
Sara SheehyAdmin
Writer | Nomad


Since today marks the second of my juice fasts for my detox, I figured it was fitting to do a post on some of the fresh juices I've been making with my Breville Juicer. If you saw my first Adventure in Juicing, you'll have noticed that I really don't follow any particular recipe, but rather just wing it. I tend to just throw in whatever ingredients I have in the house that are juiceable. Things with high juiceability. Whatever.
For today's Adventure in Juicing, I thought I'd share my most recent concoction. For the most part, I use this juice as a liquid base for making my daily smoothies (which I'll post about soon). When I'm juice fasting, I'll dilute this juice 50% with filtered water so I don't go into sugar shock.
Yeah, pretty exciting isn't it? The lemon juice helps keep the apple juice from browning and gives it a touch of tang. The ginger gives it a fresh taste and, if you go for a large chunk, a bit of kick.
As a side note, I've been so far (knock on wood) managing to fend off the latest round of cold virus that has infected the house. In spite of spending a lot of time with snotty, coughing children (and husband), I still haven't come down with it.
I'm going to partially credit my boosted immune system from everything I've been doing the last three weeks. Well, that and the elderberry.
It is very pretty. I forget that juice isn't all green. We put kale or spinach in almost everything now so it doesn't make nearly as appetizing a picture.
I am thinking about giving up that practice. I eat 3 cups of greens daily. If I just juiced carrots and apples, I could use the pulp for carrot/apple cake.
I love our juicer. During the summer when I have my garden in full swing, we have many interesting tasting juice's.
My favorite thing to do is make carrot juice to drink. I then use the carrot pulp to make carrot muffins. Taste way better than using regular grated carrots in the recipe.
Gotta love your boosted immune system. I start to get a sinus infection, drink a ton of homegrown tea's from my voodoo stash and away it goes.


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I learned on Windows but will be going very soon to 100% Apple Products!
Always been a Windows guy. For what I do, there's no need for me to switch. Just not cost effective for me.
Windows for me. I do have an I-phone and use an I-pad during baseball season, I prefer a windows based OS.
I really like the Mac but the prices are up there...Windows for now. Maybe in a few years.
My new MacBook Pro will be here Tuesday!
I think the MAC has shown over the years to be much better in sports than the PC[L]. Sorry LJ. My kids love MAC's and hate PC's.
I agree LJ.... .We should be grateful that we live within a 100 miles of Mercer Co.
different animal and if you are used to a Windows PC it will take time to adjust to the way things are set up. I have a hard time when I pick it up on the rare occasion and try to do things on it.
down. But my son swears he will never go back.
Not quite- you would have had to stop drinking wine coolers and start drinking Busch Light.
Do you have blonde hair and blue eyes? I used to think every girl in Minster had blonde hair and blue eyes. I can't tell the story that changed my mind though.
It is pretty prevalent though.
They still sell Stroh's at some places down here too.
Edited by fortfan, 10 December 2013 - 11:25 AM.
Don't be surprised. Never underestimate the importance of beer in God's country.
A few years ago I went to an event at Marion Local with a dude from work. He said he had never seen so many blonde haired kids.
Also, Blond only applies to females. Even if they are critical, I'll just say it changed from blond to gray.
Edited by LimaJock, 14 December 2013 - 11:34 AM.
Macs are better in every way.


text:
The First 40 Bugatti Divo On The Way To Owners
Divo was introduced in 2018 by Bugatti. After 2 years now this company claimed that the first ones are ready to be delivered to the customers. According to the automaker speak person: "This marks the end of a challenging development lasting almost two years,". We can see the results of the Bugatti's efforts. Divo is not just a hypercar. This car deserves much more.
Stephan Winkelmann said: "The Divo starts a new era at Bugatti – the era of modern coachbuilding". This statement is true without any doubt. The facilities of this car are much more than enough. Winkmann calls Diva as "a highly customized masterpiece of automotive craftsmanship". After Diva, Bugatti can alter and customize its others cars to be up to date. They can even transform Bugatti Chiron to Diva.
From the visual angel of view, Diva is an independent model. The profile is slimmer to give the car an appearance of flat sport car. intakes which are located on the hood, has reduced the vehicles surface area, so the airflow has a better condition. And also, with cooperation of a new spoiler, more downforce is produced. On the one hand this spoiler directs the airflow which goes into the front intakes, on the other hand by passing the air to the brakes, helps the brakes to be cooled.
The rear design is as the front so detailed and stunning. The rare has a unique 3D tail. on the tail are 44 light-up fins. Bugatti engineers considered a NACA air duct on the roof to help the 8.0-liter W16 engine, has a better air income. This engine is capable of 1,500 horsepower (1,118 kilowatts) and the top speed of this car which is recorded is 236 mile per hour (380 kilometers per hour).
Bugatti Divo Price
This car is really the combination of science, art, aerodynamics, and weird Ideas. Divo hypercar cost at least €5 million and just 40 of these cars will be built. But there is no chance for us to buy this beauty because the firm has already sold all the 40 examples.
BugattiDivoBugatti Divo


text:
Marvel's Declassified
Listen to Marvel's Declassified on Pandora - Marvel Declassified is a non-fiction narrative podcast focusing on the rich, dynamic, and evolving history of Marvel Comics - as told through a contemporary lens. Each episode is hosted by writer and comic book expert, Lorraine Cink (author of Powers of a Girl , co-author Marvel Absolutely Everything You Need to Know, and Ultimate Marvel ) and acclaimed journalist and critic Evan Narcisse (author of Marvel's Rise of the Black Panther ). Utilizing unique access to writers, artists, editors, and industry insiders who have shaped key storylines and witnessed firsthand the historical shifts within the comic book industry, we get the real story of Marvel Comics it could only be told by the House of Ideas itself.


The Murphy Center for Hope is an absolutely amazing resource in the Fort Collins community. Dedicated to helping the homeless in our town, it is a collection of 17 non-profits all contributing to this great mission. They serve 160 people every day, and help to rebuild lives and families.


Hi together, i have four Uni AP AC Pro, from the same delivery, same Age etc. (two years old). When i did the first upgrad to 4.x, three of them worked whitout any issues, the last one got briked. I did the tftp recovery and it wend back to live, but only with the old 3.9x Firmware. I tried the same with every new version, always the same, briked, back to 3.9 an it was back. Now, the controler does not accept the 3.9x FW Devices anymore, so i'm loost with this one.
Any ideas? I tryed different ways to upgrad, App, Webapp and tftp, no chance. I tried diffrent switches, diffrent ports and also POE Injectors. Also tried to switch two AP's. The good one worked on the position of the briked very well, the briked on the other side not.
Have you tried a TFTP Recovery?
So the UAP doesn't even power up correctly when you flash 4.0.15 or 4.0.21 to it?
Try to get to 3.9.54 first.
I doubt a TTL-USB cable would be of great help, but take a look yourself, not sure if the AC-Pro has the necessary headers on the board ready for use.
Did you take a look at /var/log on the AP? Probably not helpful, but who knows.
Maybe, just maybe also try with a different DNS server as issued via DHCP (UBNT has some counterfeit mechanisms in place we know nothing about).
Could be damaged flash (hardware issue) that prevents writing and/or verification.


text:
Q: Spring security : I tried to test http://localhost:8080/login Post method and I redirected to the same path for login again I have created account with spring security , I have test the functionality with Postman and my frontend it's works good, then I try to login and every time I redirected to login , it's like a problem of authorization
from frontend I get this error:
Access to XMLHttpRequest at 'http://192.168.43.216:8080/login' from origin 'http://localhost:3000' has been blocked by CORS policy: Response to preflight request doesn't pass access control check: No 'Access-Control-Allow-Origin' header is present on the requested resource.
This my WebSecurityConfig.java
    package com.pi.MinuteBrico.security.config;

import org.springframework.context.annotation.Bean;
import org.springframework.context.annotation.Configuration;
import org.springframework.security.authentication.dao.DaoAuthenticationProvider;
import org.springframework.security.config.annotation.authentication.builders.AuthenticationManagerBuilder;
import org.springframework.security.config.annotation.web.builders.HttpSecurity;
import org.springframework.security.config.annotation.web.configuration.EnableWebSecurity;
import org.springframework.security.config.annotation.web.configuration.WebSecurityConfigurerAdapter;
import org.springframework.security.crypto.bcrypt.BCryptPasswordEncoder;

import com.pi.MinuteBrico.services.AppUserService;

@Configuration
//@AllArgsConstructor
@EnableWebSecurity
public class WebSecurityConfig extends WebSecurityConfigurerAdapter {

    private final AppUserService appUserService;
    private final BCryptPasswordEncoder bCryptPasswordEncoder;

    public WebSecurityConfig(AppUserService appUserService,
            BCryptPasswordEncoder bCryptPasswordEncoder) {
        super();
        this.appUserService = appUserService;
        this.bCryptPasswordEncoder = bCryptPasswordEncoder;
    }

    @Override
    protected void configure(HttpSecurity http) throws Exception {
        http

                .cors().and()
                .csrf().disable()
                .authorizeRequests()
                    .antMatchers("/registration/**"/*,SecurityConstraint.ROLE_ALL_AUTHENTICATED_USE*/)
                    .permitAll()
                .anyRequest()
                .authenticated().and()
                .formLogin();

    }

    @Override
    protected void configure(AuthenticationManagerBuilder auth) throws Exception {
        auth.authenticationProvider(daoAuthenticationProvider());
    }

    @Bean
    public DaoAuthenticationProvider daoAuthenticationProvider() {
        DaoAuthenticationProvider provider =
                new DaoAuthenticationProvider();
        provider.setPasswordEncoder(bCryptPasswordEncoder);
        provider.setUserDetailsService(appUserService);
        return provider;
    }
}

**This what Happen when I try to test Post method for login http://localhost:8080/login on postman **
[![enter image description here][1]][1]

A: The cors (Cross Origin Resource Sharing) filter is added in your spring security configuration when you add http.cors(). This means only from same origin request will be servered. To add cross origin request to be served you need to add configuration for that. Add below bean to your SecurityConfiguration. For more deails check the link
@Bean
    CorsConfigurationSource corsConfigurationSource() {
        CorsConfiguration configuration = new CorsConfiguration();
        configuration.setAllowedOrigins(Arrays.asList("https://localhost:300")); //URLs you want to allow
        configuration.setAllowedMethods(Arrays.asList("GET","POST")); //methods you want to allow
        UrlBasedCorsConfigurationSource source = new UrlBasedCorsConfigurationSource();
        source.registerCorsConfiguration("/**", configuration);
        return source;
    }


WASHINGTON — On Wed., Oct. 29, the SAIS International Development Program in conjunction with the Foreign Policy Institute and The American Interest brought Francis Fukuyama to Kenney Auditorium for a lecture elaborating on the ideas in his latest book, Political Order and Political Decay: From the Industrial Revolution to the Globalization of Democracy.
Diving into the state of the world in 2014, he said, "it's been a terrible year. It's actually good for students of international relations because you have a lot to talk about." But from where we stand now, "the world is actually bifurcated, I think," he said. First, there is Eurasia, bookended by Russia and China, large powers on the move with their own territorial agendas and increasing self-confidence creating problems for their neighbors. Second he named the swath from North Africa through the Sub-Saharan to the Arab world, facing an opposite situation, characterized by almost the absence of states altogether, in cases like Libya, Syria, or Iraq, and neighboring states which are extremely weak.
He went on to argue that while everyone has been preoccupied with ISIS, the group "is not that powerful an actor." Rather, they are powerful only because everyone around them is weak, with many nominal governments unable to provide the basic functions of the state, from security to delivering services to the people.
Jihadism has been driven into political vacuums in places like Afghanistan, Pakistan, Yemen, the Sahel, Mali, and Cameroon where state structures are not capable of providing basic security. This has significant implications for American foreign policy: while there may be one approach for dealing with unitary states like Russia or China, in this stateless part of the world, policy has depended on America's ability to create state institutions as a way of controlling terrorism. Once entering into conflict zones, this is often the only way out, working to leave self-sustaining state structures in the place of U.S. military. Thirteen years after the attacks of September 11, "we don't seem to be terribly good at this." Regarding Iraq and Afghanistan, Fukuyama argued it is not clear that the U.S. presence is going to leave anything durable in terms of state institutions.
From examples in the current geopolitical situation, he turned to the more abstract theory of states underpinning his new work. He stressed three pillars of the political order, whose relative strength determine how countries differ around the world.
The first pillar is the state. "The state is all about power," Fukuyama said. States generate and use power to protect citizens, provide infrastructure, and deliver services to citizens. The reason Ebola has become such a severe crisis, he said, is that many of the states where it has become an epidemic either lack public health authorities or the institutions are very weak.
Second is the rule of law. "Law can be used to control a population, but rule of law as I think it's properly understood only exists if it applies to the most powerful people in a given society, the people with coercive power," Fukuyama said. If a king makes up the rules as he goes along, it may be rule by law, but it is not rule of law.
The final pillar is democratic accountability. While he noted that in the West this is often associated with elections, in a broader sense democratic accountability means that the government reflects the wider interests of people and not just the narrow interests of the elites in charge.
He went on to divide the category of "stateness," drawing on Max Weber's ideas of the modern state versus the traditional patrimonial state. The key distinction is a modern state treats its citizens impersonally, with sharp distinction between public and private interests (corruption occurs when public money is taken for private interests). In traditional patrimonial states like monarchies, kings considered themselves as personal owners of the state, and might give away a province to a daughter for a wedding present. Fukuyama believes that today there are no classic patrimonial states with rules claiming personal ownership, but there are neo-patrimonial states where coalitions of elites share rents. Those states are run for the self-interest of the people going into politics, and the distinction between public and private is completely eroded.
He went on to point out that many Americans who look at countries with corruption and elite-oriented politics "and do a lot of preaching about good governance" fail to realize the U.S. went through an extremely similar period in its early history. What the developing countries are experiencing now, "should not properly be understood as corruption, should be understood as an early form of democracy." Going back to the time of Andrew Jackson, Fukuyama argued, "the United States is the country that invented clientalism." The early American government was basically an elite body, "friends of George Washington," and a lot of Harvard and Yale graduates. Against the epitome of this group, John Quincy Adams, the "Boston Brahmin," Andrew Jackson, a frontiersman and military commander from Tennessee, personified a rise in American populism that displaced this oligarchy. "He was the Sarah Palin of his day running against the John Kerry of his day," said Fukuyama of Jackson. And in the 1820s, with a host of property-less white males newly eligible to vote, the question was, how to get them to the polls? The easiest way was to bribe them. From Christmas turkeys to jobs in the post office, "this is how Jackson got elected." It was a patronage system, every official put in place as a payoff.
As none of the actors on the inside had any interest in changing this system, Fukuyama argues that an outside triggering event was necessary for political change. In this instance, he cites the assassination of James A. Garfield by a man who was upset over losing the job of ambassador to France. According to Fukuyama, Congress was so embarrassed they voted for the Pendleton act, and the principle of merit in civil service examination. "The Chinese had invented the same system approximately 2200 years earlier," but that was the new system put in place.
In this light, democracy in some sense is the cause of the problem of clientalism, but Fukuyama believes democracy can also be the solution. Or at least that "we should hope that democracy is the solution because the other big route out of clientalism is war," which is how the Chinese state consolidated and modernized, as well as the Prussian and French empires, among others.
And then there is the danger of re-patrimonialization. Lest we think that a modern state once achieved is forever, Fukuyama warns of the problems that ensue if "you've come to worship the institutions and therefore you don't adapt adequately." This most often occurs through "insider capture," or when those in power decide "they'd much rather reward their friends and family." This tends to happen over time, all the way back to the end of Han dynasty in China. To some extent, he sees this as relevant to events in U.S. politics today. As well-organized and well-resourced interest groups proliferate, the question becomes whether or not that collectivity of interest groups adds up to something like public interest.
On a hopeful note, he said, "one of the characteristics at least in theory is that democracies can fix themselves." While in his opinion, America is not doing that right now, the soft power America's democracy projects continues to be important to other democracies around the world.